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Background: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function., Methods and Results: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m 2 . The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status ( P for interaction=0.889)., Conclusions: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Background: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results., Methods: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis., Results: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort., Conclusions: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices., (© 2024. The Author(s).)

Background: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES., Methods: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months., Results: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P =0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P =0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P =0.34) were comparable between the 2 groups., Conclusions: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157., Competing Interests: Dr Han reports grants from ChongKunDang and HanMi outside the submitted work. Dr K.W. Park reports speaker fees from Daiichi Sankyo, AstraZeneca, Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside the submitted work. Dr H.-S. Kim reports grants or speaker fees from Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Dio, Medtronic, Abbott Vascular, Edwards Life Science, Amgen, and Behringer Ingelheim outside of the submitted work. The other authors report no conflicts.

Background: Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention., Methods and Results: The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P =0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P =0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes., Conclusions: In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients., Registration: URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Background: Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI., Methods and Results: The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m 2 or >22.6 kg/m 2 ). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P =0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P =0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P =0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m 2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P =0.001). No differences were shown in major bleeding., Conclusions: HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Background: Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain., Objectives: The authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events., Methods: Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES., Results: In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis., Conclusions: In the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding., Competing Interests: Funding Support and Author Disclosures Dr Palmerini has received speaker fees from Abbott Vascular, Biotronik, and Edwards Lifesciences; and has received a research grant from Eli Lilly. Dr Abizaid is proctor for transcatheter aortic valve replacement for Boston Scientific (Acurate Neo). Dr Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia Pharmaceuticals LTD, Universität Basel Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, iVascular, Medscape, and Biotronik; and has received grants and personal fees from Terumo outside of the submitted work. Dr Morice is a shareholder and CEO of CERC, a CRO not involved in this analysis; and is a minor shareholder of Electroducer, not involved in the study either. Dr Park has received speaker’s fees from Daiichi- Sankyo, AstraZeneca, Sanofi, Bristol Myers Squibb, Bayer, and Pfizer outside of the submitted work. Dr Chieffo has received speaker/consultant fees from Abbott, Abiomed, Biosensor, Cardinal Health, GADA, and Magenta. Dr Nakamura has received grants from Daiichi-Sankyo Co, Ltd, Sanofi K.K., and Bayer K.K.; and has received fees from Daiichi-Sankyo Co, Ltd, Sanofi K.K., Terumo Corporation, Bristol Myers Squibb K.K, and Japan life line Co LTD. Dr Saia has received lecture fees from AstraZeneca, Daiichi-Sankyo, Bayer, and Boehringer Ingelheim. Dr Weisz has received consultation fees from Filterlex, Intratech, and Magenta; and has stock options in Filterlex, Intratech, Magenta, Medivizer, Trisol, and Vectorious. Dr Kirtane has received institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical; in addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for speaking engagements and/or consulting; has received personal consulting fees from Neurotronic; and has received travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr Mehran has received institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and Zoll; has received consultant fees from Boston Scientific, Cine-Med Research, Janssen Scientific Affairs, and Medscape/WebMD; has received consultant fees paid to the institution from Abbott Laboratories, Abiomed (spouse), Bayer (spouse), Beth Israel Deaconess, Bristol Myers Squibb, CardiaWave, Chiesi, Concept Medical, DSI, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, and Spectranetics/Philips/Volcano Corp; has equity <1% from Applied Therapeutics, Elixir Medical, STEL, and CONTROLRAD (spouse); has served as a consultant (no fee) for Regeneron Pharmaceuticals; and has served as Associate Editor for the ACC and AMA. Dr Stone has received speaker or other honoraria from Terumo, Cook, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Reva, MAIA Pharmaceuticals, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds. No sponsor of any of the individual trials had any role in the study design, data collection, data interpretation, or drafting the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy., Methods: HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971., Results: From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference -2·9%, p non-inferiority <0·0001; hazard ratio 0·70 [95% CI 0·52-0·92], p equivalence =0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40-1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32-0·73]; p=0·0007)., Interpretation: In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia., Funding: Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS., Hypothesis: There is wide variability in AMP use for ACS management in Asia., Methods: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months., Results: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study., Conclusions: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited., Methods: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority., Results: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority)., Conclusions: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Evaluate the safety and efficacy of guideline-recommended risk score-directed dual antiplatelet therapy (GD-DAPT) based on THE PRECISE-DAPT score after 2nd-generation drug-eluting stent (DES) implantation.Methods and Results:We analyzed 5,131 patients pooled from 4 clinical trials. Patients were divided into 3 groups according to current recommendations on the duration of DAPT and their actual DAPT duration: GD-DAPT (n=2,183), shorter DAPT (n=1,540), longer DAPT (n=1,408). The primary endpoint was the rate of net adverse clinical events (NACE) during the first 12 months. The secondary endpoints were ischemic or bleeding events. Overall, GD-DAPT did not affect NACE (1.2% vs. 1.2% for shorter DAPT and 1.7% for longer DAPT) or bleeding events (0.6% vs. 0.5% and 0.9%), and there were fewer ischemic events (2.8% vs. 4.4% and 4.0%, P=0.03) than with shorter DAPT. Especially in acute coronary syndrome (ACS) patients, GD-DAPT had fewer NACE (1.5% vs. 1.4% and 4.2%; P=0.006) and bleeding events (0.8% vs. 0.5% and 2.8%; P=0.001) than longer DAPT as well as fewer ischemic events (2.8% vs. 4.4% and 4.7%; P=0.03) than shorter DAPT., Conclusions: GD-DAPT did not affect NACE or bleeding events and reduced the number of ischemic events at 12 months compared with shorter DAPT. For ACS, GD-DAPT was associated with favorable outcomes compared with non-GD-DAPT. Therefore, GD-DAPT may optimize efficacy and safety.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome remains uncertain. This study investigated the benefit of DAPT beyond 12 months after drug-eluting stents (DES) for acute myocardial infarction (MI)., Methods: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 6199 patients treated with DAPT for 12 months after DES (second-generation DES 98%) without ischemic or bleeding events were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of death from any cause, MI, or ischemic stroke during the period from 12 to 24 months., Results: After adjustment using inverse probability of treatment weighting, patients who received DAPT beyond 12 months (n=4795), compared to patients treated with 12-month DAPT (n=1404), had a similar incidence of MACCE (1.3% vs. 1.0%, HR: 1.32, 95% CI: 0.71-2.45, p=0.378). The 2 groups did not differ significantly in the rates of death (0.1% vs. 0.1%), MI (0.8% vs.0.6%), stent thrombosis (0.1% vs. 0.2%), ischemic stroke (0.4% vs. 0.2%), and major bleeding (0.1% vs. 0.1%). The rate of net adverse clinical events was 1.4% with DAPT beyond 12 months and 1.1% with 12-month DAPT (p=0.466)., Conclusions: DAPT beyond 12 months, as compared with 12-month DAPT, in real-world patients with acute MI treated predominantly with second-generation DES did not reduce the risk of MACCE. The rates of major bleeding and net adverse clinical events did not differ significantly between the 2 treatments., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background:  The ischemic/bleeding risk of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is still uncertain. We sought to develop a tool to predict ischemic and bleeding events in East Asians receiving 2nd generation drug-eluting stents (DESs) PCI., Methods:  A pooled cohort of 13,172 East Asian patients receiving PCI with 2nd generation DES (the Grand DES cohort) was analyzed to develop a scoring system. A net score was calculated by subtracting the bleeding score from the ischemic score. External validation was performed in the HOST-ASSURE and NIPPON trials., Results:  Among the total population, ischemic and bleeding events occurred in 195 patients (1.5%) and 166 patients (1.3%), respectively. The score to predict ischemic events included previous myocardial infarction (MI) or PCI, presentation as acute MI, anemia, stent diameter < 3 mm, and total stent length of ≥30 mm, while that for bleeding events included older age, low creatinine clearance, and anemia. C-statistics of the ischemic and bleeding model was 0.708 and 0.665, respectively. Patients with a net score of ≥1 had a higher ischemic risk compared with bleeding risk, and patients with a net score of ≤-1 had a higher bleeding risk compared with ischemic risk. The validation cohort showed a C-statistic of 0.647 for ischemic events and 0.633 for bleeding events., Conclusion:  We developed a tool to predict ischemic and bleeding events in East Asian patients received PCI with 2nd generation DES. This system can be used to assess clinical event risks, and to determine the adequate duration of DAPT in East Asians., Competing Interests: Dr. Nakamura reports grants and other from Terumo Corporation, Sanofi, and Daiichi Sankyo, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized., Objectives: This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting., Methods: Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT., Results: Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: -3.86%; 95% confidence interval: -7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: -1.14%; 95% confidence interval: -2.26 to -0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity., Conclusions: Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background:  Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischaemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischaemia/bleeding risk trade-off., Methods:  We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischaemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335)., Results:  Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p  < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p  = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p  = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p  = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischaemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischaemia was significantly higher in East Asians (32.3% vs. 0.4%, p  < 0.001)., Conclusion:  We suggest that the ischaemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischaemic risk, while significantly increases the bleeding risk., Competing Interests: Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott); Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, PLx Pharma, Takeda. Marco Valgimigli reports grants from AstraZeneca; personal fees from AstraZeneca, grants and personal fees from Terumo, personal fees from Abbott Vascular, personal fees from Bayer, personal fees from Amgen, personal fees from Cardinal health, personal fees from Biosensors, personal fees from Abbott Vascular, personal fees from Daiichi Sankyo, outside the submitted work. All the other authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: The aim of this study was to investigate clinical outcomes after left main coronary artery (LM) bifurcation percutaneous coronary intervention (PCI) and the impact of the duration of dual antiplatelet therapy (DAPT) according to treatment strategy., Background: There are limited data regarding the optimal PCI strategy for LM bifurcation lesions with new-generation drug-eluting stents., Methods: A patient-level pooled analysis of 5 nationwide multicenter registries was performed. Rates of target lesion failure, thrombotic adverse cardiovascular events, and their individual components at 3-year were analyzed. Subgroup analysis according to DAPT duration was performed., Results: From 13,172 patients undergoing PCI with new-generation drug-eluting stents, a total of 700 patients were treated for LM bifurcation lesions, 567 with a 1-stent strategy and 133 with a 2-stent strategy. Rates of target lesion failure and target lesion revascularization were higher in the 2-stent group, driven mainly by complex lesion profiles. Risks for thrombotic adverse cardiovascular events and its components were comparable between the 2 strategies. Subgroup analysis showed that risks for target lesion failure and thrombotic adverse cardiovascular events in the 2-stent group were significantly higher than in the 1-stent group in those with DAPT interruption <1 year, while they were similar in those receiving DAPT maintenance ≥1 year., Conclusions: Up to 20% of patients who underwent LM bifurcation PCI eventually required a 2-stent strategy, which was as safe as a 1-stent strategy with the use of new-generation drug-eluting stents. Careful pre-emptive case selection as well as prolonged DAPT may be necessary when considering a 2-stent strategy in LM PCI given its higher rate of repeat revascularization and lesion failure than the 1-stent approach., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated optimal duration of dual antiplatelet therapy (DAPT) after second-generation drug-eluting stent (DES) implantation in acute coronary syndrome (ACS)., Material and Methods: From pooled analysis of three randomized clinical trials (EXCELLENT, IVUS-XPL, RESET), a total of 2,216 patient with ACS undergoing second-generation DES implantation were selected. Each study randomized patients to a short-duration DAPT arm (n = 1119; ≤6 months) or a standard-duration DAPT arm (n = 1097; ≥12 months). Two-thirds of patients were male, and their mean age was 63 years. Mean DAPT durations were 164 ±76 and 359 ±68 days, respectively. The primary endpoint was composite of cardiac death, myocardial infarction, stent thrombosis, stroke or major bleeding during the first 12 months after implantation, analyzed according to the intention-to-treat population., Results: Demographic characteristics were balanced between groups. Mean DAPT duration was 164 and 359 days, respectively. Primary endpoint occurred in 22 patients with short-DAPT and 21 patients with standard-DAPT (2.0% versus 1.9%; hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.56-1.86; p = 0.94). Landmark analysis after six-months, no significant difference in primary endpoint between short and standard duration DAPT (1.0% versus 0.8%; HR 1.22; 95% CI 0.51-2.95; p = 0.66)., Conclusions: Short-duration DAPT (≤6 months) demonstrated a similar incidence of net adverse cardiovascular and clinical events at 12 months after second-generation DES in ACS compared with standard duration DAPT (≥12 months)., Clinical Trial Registration: EXCELLENT (ClinicalTrials.gov, NCT00698607), RESET (ClinicalTrials.gov, NCT01145079), IVUS-XPL (ClinicalTrials.gov, NCT01308281)., Competing Interests: The authors have declared that no competing interests exist.

Background: Dual antiplatelet therapy (DAPT) is recommended in patients receiving drug-eluting stents (DES). However, bleeding risk should be weighed against ischemic risk. Utility of GRACE risk score and ACUITY-HORIZONS bleeding risk score was assessed in patients with acute myocardial infarction (MI) according to use of P2Y12 blocker., Methods: From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 7791 patients with acute MI receiving DES were divided into ticagrelor (n=1554) and clopidogrel (n=6237) groups. Propensity-matched 12-month mortality and bleeding event rates were compared according to GRACE and ACUITY-HORIZONS scores. Patients who received thrombolysis, prasugrel or anticoagulants, or who discontinued or switched DAPT were excluded., Results: In all patients, high-risk patients more often received clopidogrel. After propensity score matching (n=1553 in each group), 12-month mortality was not different, but TIMI major bleeding rate was higher with ticagrelor (2.8% vs. 1.4%, p=0.007). On subgroup analysis, 12-month mortality was lower with ticagrelor in patients with high (>140) compared to low-to-moderate risk GRACE score (5.1% vs. 7.9%, p=0.04). When combined with ACUITY-HORIZONS bleeding score, 12-month mortality was lower with ticagrelor in patients with high GRACE score but without very high (≥20) ACUITY-HORIZONS score (2.4% vs. 5.3%, p=0.03)., Conclusions: In patients with acute MI receiving DES, GRACE and ACUITY-HORIZONS scores may help guide DAPT. In patients with high GRACE score, a more potent P2Y12 blocker may be considered, particularly in the subset not at very high risk of bleeding., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Whether prolonged dual antiplatelet therapy (DAPT) improves clinical outcomes after percutaneous coronary intervention for coronary bifurcation lesion is uncertain., Methods and Results: We evaluated 2082 patients who were treated with drug-eluting stent for bifurcation lesions and were event free (no death, myocardial infarction [MI], cerebrovascular accident, stent thrombosis, or any revascularization) at 12 months after the index procedure. Patients were divided into 2 groups: DAPT ≥12-month group (n=1776) and DAPT <12-month group (n=306). Primary outcome was all-cause death or MI. At 4 years after the index procedure, death or MI occurred less frequently in the DAPT ≥12-month group than the DAPT <12-month group (2.8% versus 12.3%; adjusted hazard ratio, 0.21; 95% confidence interval, 0.13-0.35; P <0.001). After propensity score matching, incidence of death or MI was still lower in the DAPT ≥12-month group than the DAPT <12-month group (2.6% versus 12.3%; adjusted hazard ratio, 0.22; 95% confidence interval, 0.12-0.38; P <0.001). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of lesion location, stenting technique, or type of used drug-eluting stent., Conclusions: The risk of all-cause death or MI was significantly lower in the ≥12-month DAPT group than the <12-month DAPT group after percutaneous coronary intervention for bifurcation lesion using drug-eluting stent. Our results suggest that prolonged DAPT may improve long-term clinical outcomes after percutaneous coronary intervention for bifurcation lesions., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01642992., (© 2018 American Heart Association, Inc.)

Objectives: This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients., Background: Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited., Methods: Using 6 randomized trials that compared short-term (≤6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients (≥65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding., Results: The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p = 0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction = 0.0384). In the subset of younger patients (<65 years of age, n = 6,152), short-term DAPT was associated with higher risk of primary outcome (HR: 1.67; 95% CI: 1.14 to 2.44; p = 0.0082). In elderly patients (n = 5,319), however, the risk of primary outcome did not significantly differ between patients receiving short-term and long-term DAPT (HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.2856). Short-term DAPT was associated with a significant reduction in major bleeding compared with long-term DAPT (HR: 0.50; 95% CI: 0.30 to 0.84; p = 0.0081) in the overall group, and particularly in elderly patients (HR: 0.46; 95% CI: 0.24-0.88; p = 0.0196)., Conclusions: Short-term DAPT after new-generation DES implantation may be more beneficial in elderly patients than in younger patients., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although there have been several reports that prasugrel can improve clinical outcomes, the efficacy and safety of prasugrel is unknown in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization., Methods: A total of 4421 patients [637 patients were prescribed prasugrel (60/10 or 5mg, loading/maintenance dose) and 3784 patients clopidogrel (600 or 300/75mg)] with AMI undergoing successful revascularization were enrolled from the core clinical cohort of Korea Acute Myocardial Infarction Registry-National Institute of Health., Results: After propensity score matching (637 pairs), there were no significant differences in baseline clinical and procedural characteristics and in-hospital medications between the two groups. The primary efficacy endpoint, defined as the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months showed no significant difference between prasugrel and clopidogrel (2.4% vs. 2.9%, p=0.593). Also, no difference was observed in the composite of cardiac death, MI, or stroke during hospitalization between two groups (0.8% vs. 0.9%, p=0.762). However, the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding was significantly higher in prasugrel compared with clopidogrel (5.3% vs. 2.7%, p=0.015). In multivariate linear regression analysis, trans-femoral intervention, use of glycoprotein IIb/IIIa inhibitors, use of calcium channel blocker, and use of prasugrel were independent predictors of in-hospital TIMI major or minor bleeding [odds ratio (OR)=6.918; 95% confidence interval (CI)=2.453-19.510, OR=2.577; 95% CI=1.406-4.724, OR=4.016; 95% CI=1.382-11.668, OR=2.022; 95% CI=1.101-3.714]., Conclusions: Our study shows that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events compared with clopidogrel. However, further large-scale, long-term, randomized clinical trials are required to accurately assess the efficacy and safety of prasgurel and to find out the optimal dose for Korean AMI patients., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

Introduction: We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies., Methods and Analysis: The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding., Ethic Approval and Dissemination: All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers., Trial Registration Number: NCT02601157; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials., Background: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events., Methods: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke., Results: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p = 0.52; absolute risk difference 0.10%; 95% CI: -0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p = 0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term (≥12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p < 0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction = 0.036)., Conclusions: Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term (≥12 months) DAPT exposure., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Current 2nd-generation drug-eluting stents (DES) have dramatically improved clinical outcomes after percutaneous coronary intervention for coronary artery disease. However, DES implantation has major long-term limitations related to the permanent presence of foreign material in the coronary artery. Bioresorbable vascular scaffolds (BVS) were designed to overcome this limitation of permanent metal-based DES. However, because of immature manufacturing technology, BVS have several drawbacks, such as the thicker strut, poor deliverability, poor radio-opacity, poor radial strength, and cumbersome procedure to meet the principle of PSP (Preparation, Sizing, and Post-dilatation). Initial studies indicated that BVS outcomes were non-inferior to those of current DES and recent follow-up data of trials have revealed an additional critical drawback, higher rate of scaffold thrombosis, on the top of the existing limitations of BVS. Thus attention must be paid to the appropriate BVS-specific implantation protocols (i.e., PSP), as well as adequate intensity and duration of dual antiplatelet therapy. In any case, current BVS need further technical evolution to replace current metallic DES in routine clinical use.

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST-ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n = 725) or non-CYP3A4-metabolized statin group (group B, n = 462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: -15 ± 79, p < 0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, -62 ± 78, p < 0.001; group B, -59 ± 69, p < 0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.

Background: Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear., Objectives: The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs., Methods: RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded., Results: Individual patient data were obtained for 6 RCTs, and aggregate data were available for 12 RCTs. Patients with bleeding had significantly higher rates of mortality compared with those without, and in a time-adjusted multivariate analysis, bleeding was an independent predictor of mortality occurring within 1 year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53 to 10.60; p < 0.0001). Shorter DAPT was associated with lower rates of all-cause death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval: 0.73 to 1.00; p = 0.05), which was driven by lower rates of bleeding-related deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95% confidence interval: 0.43 to 0.99; p = 0.04). Mortality unrelated to bleeding was comparable between the 2 groups. Similar results were apparent in the modified intention-to-treat population., Conclusions: Bleeding was strongly associated with the occurrence of mortality within 1 year after the bleeding event. Shorter compared with longer DAPT was associated with lower risk for bleeding-related death, a finding that may underlie the lower all-cause mortality with shorter DAPT in the RCTs of different DAPT durations after DES., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation., Methods and Results: We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS., Conclusions: Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y 12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose., Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk., Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (p interaction =0·007), and exerted a significant ischaemic benefit only in this latter group., Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation., Trial Design: The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization., Conclusions: The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Whether the efficacy and safety of dual antiplatelet therapy (DAPT) are uniform between sexes is unclear. We sought to compare clinical outcomes between short- (≤6 months) versus long-term (≥1 year) DAPT after drug-eluting stent (DES) placement in women and men., Methods and Results: We pooled individual patient data from 6 randomized trials of DAPT (EXCELLENT, OPTIMIZE, PRODIGY, RESET, SECURITY, ITALIC PLUS). The primary outcome was 1-year risk of major adverse cardiac events (MACE). The main secondary outcome was 1-year risk of any bleeding. Out of the 11,473 randomized patients included in the pooled dataset, 3,454 (30%) were females. At 1-year follow-up, women had higher risk of MACE (3.6% vs. 2.8%; P = 0.01) but similar risk of bleeding (1.9% vs. 1.6%; P = 0.16) as compared with men. Compared with long-term DAPT, short-term DAPT was associated with similar rates of MACE in both women (HR 0.88; 95% CI 0.62-1.25) and men (HR 1.25; 95% CI 0.95-1.6; P interaction = 0.08)]. At 1-year follow-up, short-term DAPT was associated with lower rates of bleeding as compared with long-term DAPT in both women (HR 0.84; 95% CI 0.51-1.37) and men (HR 0.58; 95% CI 0.40-0.84; P-interaction = 0.25). The presence of MVD was associated with higher MACE rates in the short-term DAPT group in women (HR: 1.16; CI 0.60-2.23) and men (HR: 2.29; CI 1.22-4.29; P interaction = 0.25)., Conclusions: Short-term DAPT is associated with similar rates of MACE but lower risk of bleeding when as compared with prolonged DAPT. There was no significant difference between sexes in the population studied. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: There is general agreement that the optimal duration of dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents should be individualized. We hypothesized that the extent of coronary artery disease may affect the clinical outcomes of DAPT., Methods and Results: We pooled patient-level data from 5 large, randomized trials comparing short-term DAPT with prolonged therapy. From the data, we identified 5476 patients who received newer-generation drug-eluting stents. Net adverse clinical event (NACE) was defined as a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding. At 1 year, NACE had occurred in 171 patients (3.1%). Independent predictors of NACE were older age (>65 years), sex, presence of diabetes mellitus, left ventricular dysfunction (ejection fraction <40%), and angiographic multivessel disease. Multivessel disease and DAPT duration were significantly associated with NACE (P for interaction=0.002); the association was driven by the greater occurrence of myocardial infarction in patients with multivessel disease. In patients with multivessel disease, 6-month DAPT (versus 12-month DAPT) was associated with a higher incidence of myocardial infarction (adjusted hazard ratio=2.748; 95% confidence interval=1.375-5.491; P=0.004), compared with patients with single-vessel disease (P for interaction=0.001)., Conclusions: In patients treated with newer-generation drug-eluting stents, a significant interaction between DAPT strategy and multivessel disease was found regarding the occurrence of NACE at 1 year. Among adverse events, myocardial infarction was more frequent in 6-month DAPT than in 12-month DAPT in patients with multivessel disease., (© 2016 American Heart Association, Inc.)

Background: Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear., Objectives: This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity., Methods: The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach., Results: Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p < 0.0001). Compared with short-term DAPT, long-term DAPT yielded significant reductions in MACE in the complex PCI group (adjusted HR: 0.56; 95% CI: 0.35 to 0.89) versus the noncomplex PCI group (adjusted HR: 1.01; 95% CI: 0.75 to 1.35; p interaction  = 0.01). The magnitude of the benefit with long-term DAPT was progressively greater per increase in procedural complexity. Long-term DAPT was associated with increased risk for major bleeding, which was similar between groups (p interaction  = 0.96). Results were consistent by per-treatment landmark analysis., Conclusions: Alongside other established clinical risk factors, procedural complexity is an important parameter to take into account in tailoring upfront duration of DAPT., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU)., Background: PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity., Methods: Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU., Results: A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813)., Conclusions: The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Fixed-dose combination (FDC) drugs can simplify the medication regimen and potentially improve adherence. However, evidence is lacking about the efficacy and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the three independent MR-CAPCIS trials were pooled and analysed. In those trials, subjects who had been treated with either dual antiplatelet therapy (DAPT) or aspirin alone after drug-eluting stent (DES) implantation were randomly assigned to one-pill or to two-pill DAPT group. Platelet reactivity was measured with VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks after treatment. In the present study, primary efficacy endpoint was changes in platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965 subjects were analysed. In prior clopidogrel and aspirin users, PRU was well maintained regardless of switching to either one-pill or two-pill DAPT (ΔPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7 in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between them (p=0.499). The incidence of high on-treatment platelet reactivity at eight weeks, defined as PRU≥235 in Western people, was 34.8 % in one-pill DAPT group and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU ≥275 in Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high platelet reactivity on clopidogrel were female gender, increasing age, and diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT showed similar efficacy to two-pill DAPT in terms of platelet reactivity in patients receiving DES in Korea.

Background: Antiplatelet treatment is an important component in optimizing the clinical outcomes after percutaneous coronary intervention (PCI) especially in patients with acute coronary syndrome (ACS). Prasugrel, which is a new P2Y12 inhibitor, has been confirmed as efficacious in a large trial in Western countries, and a similar trial is also to be launched in Asian countries. Although a 60-mg loading dose of prasugrel followed by 10 mg per day should be acceptable, there have been no data regarding the optimal dose in Asian patients. Furthermore, serum levels of prasugrel and the rates of platelet inhibition are known to be higher in Asians than Caucasians with the same dose of the drug. Polymer, a key component of drug-eluting stents (DES), has been suggested as the cause of inflammation leading to late complications, and has driven many companies to develop biodegradable-polymer DES. Currently, there are limited data regarding the head-to-head comparison between BP-BES and the biostable polymer CoCr-EES or the newest platinum-chromium everolimus-eluting stent (PtCr-EES). Furthermore, the polymer issue may be more important in ACS where there is ruptured thrombotic plaque where polymer-induced inflammation may affect the local milieu of the stented artery. Therefore, the present study dedicated only to ACS patients, will offer important information on the optimal prasugrel dose in the Asian population by comparing a 10-mg versus a 5-mg maintenance dose beyond 1 month after PCI, as well as giving important insight into the polymer issue by comparing BP-BES versus biostable-polymer PtCr-EES., Method/design: Harmonizing Optimal Strategy for Treatment of coronary artery diseases--comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS) trial is a multicenter, randomized and open-label clinical study with a 2 × 2 factorial design, according to the type of stent (PtCr-EES versus BP-BES) and prasugrel maintenance dose (5 mg versus 10 mg), to demonstrate non-inferiority of PtCr-EES relative to BP-BES or the reduced prasugrel dose relative to conventional dose in an Asian all-comers PCI population presenting with ACS. Approximately 3400 patients will undergo prospective, random assignment separately to either stent or prasugrel arm (1:1 ratio, respectively). When the patients have contraindications to prasugrel, they are categorized into an antiplatelet observation group after stent-randomization. The primary endpoint is the patient-oriented composite outcome, which is a composite of all-cause mortality, any myocardial infarction (MI), any repeat revascularization in the stent arm at 12 months after index PCI. In the prasugrel arm, primary endpoint is any major adverse cardiovascular event, which is a composite of all-cause mortality, any MI, any stent thrombosis (Academic Research Consortium (ARC)-defined), any repeat revascularization, stroke, or bleeding (BARC class ≥ 2)., Discussion: The HOST-REDUCE-POLYTECH-ACS RCT is the first study exploring the optimal maintenance dose of prasugrel beyond 1 month after PCI for ACS in Asian all-comers. In addition, this is the largest study dedicated only to ACS patients to evaluate the polymer issue in the situation of ACS by directly comparing biostable-polymer PtCr-EES versus BP-BES., Trial Registration: ClinicalTrials.gov (ID: NCT02193971, 13 July 2014).

Background: The optimal duration of dual antiplatelet therapy (DAPT) remains controversial in patients with acute coronary syndrome (ACS). We sought to compare outcomes after the implantation of zotarolimus-eluting stent (ZES) between patients with ACS who received clopidogrel-based DAPT for >6months and those treated for ≤6months., Methods: From a registry of patients treated with ZESs between October 2005 and January 2010, 1740 patients with ACS were selected for the present analysis. Landmark analyses were performed for ACS patients who were event-free at 6months follow-up (n=1674). The primary outcome was a major adverse cardiac and cerebrovascular event (MACCE), including all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis, or stroke. We also performed adjustments for the baseline characteristics of patients, using their propensity-score matching (n=469 pairs)., Results: During a median follow-up of 22.5months, the rate of MACCE was 6.4% in patients with DAPT >6months (n=1140) and 4.7% in patients with DAPT ≤6months (n=534) (adjusted hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.61-1.82; p=0.86). After propensity-score matching, DAPT >6months was not found to be associated with a lower incidence of MACCE compared with DAPT ≤6months (adjusted HR 0.80, 95% CI 0.44-1.45, p=0.46). The rates of all-cause death or MI, TVR, stent thrombosis, and stroke also did not differ significantly between two groups., Conclusion: DAPT for >6months do not seem to be associated with improved clinical outcomes in patients with ACS undergoing percutaneous coronary intervention (PCI) with ZES., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: In-hospital and postdischarge mortality for acute coronary syndromes (ACS) vary across Asia and remain generally poorer than globally. The relationship between real-life antithrombotic management patterns (AMPs) and ACS-related outcomes in Asia is unclear., Methods: EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post-index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up., Results: Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208)., Conclusions: EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described., (© 2015 Wiley Periodicals, Inc.)

Background: The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation., Methods/design: The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment., Discussion: The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM., Trial Registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643)., (Copyright © 2015. Published by Elsevier Inc.)

The efficacy and safety of adding cilostazol to aspirin plus clopidogrel (triple antiplatelet therapy, TAPT) have not been fully evaluated in complex percutaneous coronary intervention (PCI). We sought to investigate whether TAPT after PCI for bifurcation lesions improves long-term clinical outcomes. Consecutive patients undergoing PCI for bifurcation lesions were enrolled from 18 centers in Korea between 2003 and 2009. We compared target vessel failure (TVF), defined as a composite of cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR), among 675 patients who received TAPT and 2081 who received dual antiplatelet therapy (DAPT: aspirin plus clopidogrel). Patients who received TAPT had more cardiovascular co-morbidities with regard to clinical, angiographic, and procedural characteristics. During the follow-up (median 36 months), 346 (12.6%) TVFs occurred. The incidence of TVF was significantly higher in the TAPT group, mainly driven by a higher TVR rate. In the TAPT group, however, the risk of TVF was not significantly different from the DAPT group after adjusting for the confounders of TVFs (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.53-1.39, p = 0.53). And also, there were no significant differences between the 2 groups in terms of the risks for death, cardiac death, MI, TVR, stent thrombosis, or cerebrovascular accident. These results were consistent after propensity score-matched analysis, and were also constant among the high-risk subgroups. TAPT after bifurcation PCI had no beneficial effect on the risk of long-term clinical outcomes in real-world clinical practice. Further studies are needed to confirm these findings.

Background: Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies., Methods: We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches., Findings: We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT., Interpretation: Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE)., Objectives: This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis., Methods: Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis)., Results: Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT., Conclusions: Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to test whether the newly developed platinum chromium (PtCr)-based everolimus-eluting stent (EES) is noninferior to the cobalt chromium (CoCr)-based zotarolimus-eluting stent (ZES) in all-comers receiving percutaneous coronary intervention (PCI)., Background: PtCr provides improved radial strength, conformability, and visibility compared with the CoCr alloy, but PtCr-based stents have not been tested in a wide range of patients receiving PCI. Also, recent case series have raised the issue of longitudinal stent deformation (LSD) with newer drug-eluting stents., Methods: We randomly assigned 3,755 all-comers receiving PCI to PtCr-EES or CoCr-ZES. The primary outcome was target lesion failure (TLF) at 1-year post-PCI, defined as the composite of cardiac death, nonfatal target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization. Post-hoc angiographic analysis was performed to qualitatively and quantitatively analyze LSD., Results: At 1 year, TLF occurred in 2.9% and 2.9% of the population in the PtCr-EES and CoCr-ZES groups, respectively (superiority p = 0.98, noninferiority p = 0.0247). There were no significant differences in the individual components of TLF as well as the patient-oriented clinical outcome. Of 5,010 stents analyzed, LSD occurred in 0.2% and 0% in the PtCr-EES and CoCr-ZES groups, respectively (p = 0.104). There was no significant difference in post-deployment stent length ratio between the 2 stents (p = 0.352)., Conclusions: At 1 year, PtCr-EES was noninferior to CoCr-ZES in all-comers receiving PCI. Although LSD was observed only in PtCr-EES, both the stent length ratio and the frequency of LSD were not significantly different between the 2 stent types, and PtCr-EES was not associated with adverse clinical outcomes. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention., Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin(20 mg/day, n=295) or rosuvastatin(10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit(PRU) values at both discharge and six months. We compared the P2Y12 reaction unit(PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450(CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups., Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge(atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p=0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months(atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p=0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles((＊)2 or (＊)3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin(p for interaction=0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of ＞273(the highest tertile)(OR 1.67, 95% confidence interval 1.05-2.65, p=0.031)., Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.

Background: Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. There are no data, however, on the antiplatelet efficacy and tolerability of clopidogrel napadisilate in coronary artery disease (CAD) patients., Objective: The aim of this study is to demonstrate that the combination therapy of aspirin and clopidogrel napadisilate is not inferior to that of aspirin and clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation, if it is given for 4 weeks to CAD patients who had been treated with a drug-eluting stent more than 12 months prior and had remained in a stable condition with a single antiplatelet agent, aspirin., Methods: This study was a prospective, randomized, double-blind, double-dummy, parallel-group, phase IV clinical trial. A total of 162 patients were prospectively recruited from three centers. The subjects were randomized to either the test group that was treated with 75 mg of clopidogrel napadisilate once daily or to the control group that was treated with 75 mg of clopidogrel bisulfate once daily. The primary outcome was the percent inhibition of the platelet aggregation change after the medication, as assessed by a VerifyNow™ P2Y12 assay. The secondary outcome was the change in P2Y12 reaction units (PRUs) from the baseline to the end of 4 weeks of treatment. The prevalence of adverse events was assessed at each visit through a direct interview., Results: The mean increase in the percent inhibition after 4 weeks of treatment was 19.4 % in the clopidogrel napadisilate group and 19.5 % in the clopidogrel bisulfate group. The lower bound of the 95 % two-sided confidence interval for the difference in the change between the two groups (-5.46) was greater than the pre-defined non-inferiority margin of (-10.5). Therefore, clopidogrel napadisilate was deemed non-inferior to clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation. The PRU decreased by 73.1 ± 30.7 in the clopidogrel napadisilate group, which decreased by -7.8 more than in the clopidogrel bisulfate group (65.3 ± 62.1); but the difference between the two groups was statistically insignificant (p = 0.435). There was no significant difference in the drug-related adverse events between the two groups (12.3 vs. 10.1 %; p = 0.804)., Conclusion: The platelet inhibitory efficacy of clopidogrel napadisilate is not inferior to that of clopidogrel bisulfate. There were also no statistically significant differences between the two treatment groups in the safety analyses. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in stable CAD patients who have undergone a drug-eluting stent placement., Clinical Trial Registration: Registered at ClinicalTrials.gov as NCT01830491.