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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: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months., Methods: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529)., Results: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments., Conclusions: In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tantry has received honoraria from Wolters Kluwer Pharma. Dr. Farkouh received research grant support from Astra Zeneca and Novartis and served as a consultant to Otitopic. Dr. Gurbel has received consulting fees and/or honoraria from Bayer, Vectura/Otitopic, Janssen, Cleveland Clinic foundation, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, Premier Health Care Resource, Baim Institute, and Medforce; institutional research grants from Accriva Diagnostics, AstraZeneca, Bayer, Cronos, Haemonetics, Hikari Dx, Idorisa, Labcorp Drug Development, Novartis, Prolocor, Recor Medical, Vectura Limited, Zoll Medical Corporation; in addition, Dr. Gurbel has two patents, Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient. Dr. Gurbel was an expert witness in a lawsuit associated with Plavix. Dr Bonaca has received consulting fees/honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, outside the submitted work. oung-Hoon Jeong reports honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo, Otsuka, Han-mi Pharmaceuticals, Yuhan Pharmaceuticals, and research grants or support from AstraZeneca, Han-mi Pharmaceuticals, Yuhan Pharmaceuticals, and Haemonetics. Dr Navarese received speaker fees from Astra-Zeneca, outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI)., Methods: In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years., Results: High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010)., Conclusions: In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA., Methods: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025., Conclusions: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD., Trial Registration: URL: https://www., Clinicaltrials: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457., Competing Interests: Conflicts of Interest The authors declare no disclosures or conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.

Aims: Randomized controlled trials (RCTs) testing bleeding reduction strategies using antiplatelet treatment regimens (BRATs) in acute coronary syndromes (ACS) have shown promising results, but the generalizability of these findings may be significantly influenced by the ethnicity of the patients enrolled, given that East Asian (EA) patients show different ischaemic-bleeding risk profile compared to non-EA patients., Methods and Results: RCTs comparing a BRAT vs. standard 12-month dual antiplatelet therapy (DAPT) in patients with ACS undergoing percutaneous coronary intervention (PCI) were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) as defined in each trial and the primary safety endpoint was minor or major bleeding. Twenty-six RCTs testing seven different BRATs were included. The only strategy associated with a trade-off in MACE was 'upfront unguided de-escalation' in the subgroup of non-EAs (risk ratio 1.16, 95% confidence interval 1.09-1.24). All but aspirin monotherapy-based strategies (i.e. 'short and very short DAPT followed by aspirin') were associated with reduced bleeding compared with standard DAPT in both EA and non-EA patients. There were no significant differences between subgroups, but the lack of RCTs in some of the included strategies and the difference in the certainty of evidence between EA and non-EA patients revealed that the evidence in support of different BRATs in ACS undergoing PCI is influenced by ethnicity. Moreover, absolute risk reduction estimation revealed that some BRATs might be more effective than others in reducing bleeding according to ethnicity., Conclusion: The majority of BRATs are associated with reduced bleeding without any trade-off in hard ischaemic endpoints regardless of ethnicity. However, the supporting evidence and relative safety profiles of different BRATs might be significantly affected by ethnicity, which should be taken into account in clinical practice., Study Registration: This study is registered in PROSPERO (CRD42023416710)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated., Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5., Results: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group., Conclusion: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry., Trial Registration: ClinicalTrials.gov Identifier: NCT04734028., Competing Interests: Dr. Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals, as well as research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr. Song has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Bayer Korea, and Samjin Pharmaceutical. Dr. Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK inno. N Pharmaceuticals, and DIO Medical Ltd. The other authors have no potential conflicts of interest to declare., (© 2024 The Korean Academy of Medical Sciences.)

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028., (© 2024. The Author(s).)

Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P  = .156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P -value .663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P -value .262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028., Competing Interests: Declaration of Conflicting InterestsDr. Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals, as well as research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr. Song has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Bayer Korea, and Samjin Pharmaceutical. Dr. Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK Inno. N Pharmaceuticals, and DIO Medical Ltd. The other authors have no potential conflicts of interest to disclose.

Background: The benefits of de-escalation of P2Y 12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status., Aims: We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status., Methods: This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria., Results: A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84)., Conclusions: In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y 12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y 12 ) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y 12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y 12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes., (© 2023. Springer Nature Limited.)

Background: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients., Methods: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke., Results: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and Hb A1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HR adj ]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HR adj : 1.507; 95% CI: 1.193-1.902; P < 0.001)., Conclusion: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients., Clinical Trial Registration: URL: https://www., Clinicaltrials: gov . Unique identifier: NCT04734028., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: After a brief period of dual antiplatelet therapy, P2Y 12 inhibitor monotherapy in the absence of aspirin effectively reduces bleeding without increasing recurrent ischemia in patients undergoing percutaneous coronary intervention (PCI). In addition, early anti-inflammatory therapies may have clinical benefits in acute coronary syndrome (ACS) patients., Objectives: The aim of this study was to investigate the feasibility of ticagrelor or prasugrel P2Y 12 inhibitor monotherapy combined with colchicine immediately after PCI in patients with ACS., Methods: This was a proof-of-concept pilot trial. ACS patients treated with drug-eluting stents were included. On the day after PCI, low-dose colchicine (0.6 mg daily) was administered in addition to ticagrelor or prasugrel maintenance therapy, whereas aspirin therapy was discontinued. The primary outcome was any stent thrombosis at 3 months. The key secondary outcomes were platelet reactivity measured by the VerifyNow assay (Accriva) before discharge and a reduction in high-sensitivity C-reactive protein (hs-CRP) over 1 month., Results: We enrolled 200 patients, 190 (95.0%) of whom completed the 3-month follow-up. The primary outcome occurred in 2 patients (1.0%): 1 definite and 1 probable stent thrombosis. The level of platelet reactivity overall was 27 ± 42 P2Y 12 reaction units, and only 1 patient had high platelet reactivity (>208 P2Y 12 reaction units). The hs-CRP levels decreased from 6.1 mg/L (IQR: 2.6-15.9 mg/L) at 24 hours after PCI to 0.6 mg/L (IQR: 0.4-1.2 mg/L) at 1 month (P < 0.001), and the prevalence of high-inflammation criteria (hs-CRP ≥2 mg/L) decreased from 81.8% to 11.8% (P < 0.001)., Conclusions: In ACS patients undergoing PCI, it is feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after PCI in addition to ticagrelor or prasugrel P2Y 12 inhibitors. This approach is associated with favorable platelet function and inflammatory profiles. (Mono Antiplatelet and Colchicine Therapy [MACT]; NCT04949516)., Competing Interests: Funding Support and Author Disclosures This study was supported by the Cardiovascular Research Center, Seoul, Korea. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, and Han-mi Pharmaceuticals; and has received research grants or support from Yuhan Pharmaceuticals, Han-mi Pharmaceuticals, Sam-jin Pharmaceuticals, Biotronik, and U and I Corporation. Dr Gorog has received institutional research grants from AstraZeneca, Werfen, Medtronic, Bayer, and Alpha MD; and has received speaker fees from AstraZeneca. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background:  Guideline-recommended dual antiplatelet therapy (DAPT; aspirin plus prasugrel/ticagrelor) for 12 months in acute coronary syndrome (ACS) patients increases bleeding, with East Asians (EAs) exhibiting higher bleeding and lower ischemic risk, compared with non-East Asians (nEAs). We sought to compare DAPT "de-escalation" strategies in EA and nEA populations., Methods:  A systematic review and meta-analysis of randomized controlled trials assessing reduction of DAPT intensity or duration in ACS patients undergoing percutaneous coronary intervention, in EA and nEA, was performed using a random-effects model., Results:  Twenty-three trials assessed reduction of DAPT intensity ( n  = 12) or duration ( n  = 11). Overall, reduced DAPT intensity attenuated major bleeding (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65-0.94, p  = 0.009), without impacting net adverse cardiovascular events (NACE) or major adverse cardiovascular events (MACE). In nEA, this increased MACE (OR: 1.20, 95% CI: 1.09-1.31, p  < 0.0001) without impacting NACE or bleeding; while in EA, it reduced major bleeding (OR: 0.71, 95% CI: 0.53-0.95, p  = 0.02) without affecting NACE or MACE. Overall, abbreviation of DAPT duration reduced NACE (OR: 0.90, 95% CI: 0.82-0.99, p  = 0.03) due to major bleeding (OR: 0.69, 95% CI: 0.53-0.99, p  = 0.006), without impacting MACE. In nEA, this strategy did not impact NACE, MACE, or major bleeding; while in EA, it reduced major bleeding (OR: 0.60, 95% CI: 0.4-0.91, p  = 0.02) without impacting NACE or MACE., Conclusion:  In EA, reduction of DAPT intensity or duration can minimize bleeding, without safety concerns. In nEA, reduction of DAPT intensity may incur an ischemic penalty, while DAPT abbreviation has no overall benefit., Competing Interests: D.A.G. has received institutional grants from Bayer Plc, AstraZeneca, Werfen, Medtronic, and AlphaMD and honoraria for lectures from AstraZeneca and Boehringer Ingelheim. E.P.N. has received speaker fees from Astra-Zeneca, Bayer, Amgen, and Sanofi-Regeneron. Y-.H.J. has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals, Han-mi Pharmaceuticals, Sam-jin Pharmaceuticals, Biotronik, and U&I Corporation. All other authors have no disclosures to declare., (Thieme. All rights reserved.)

Purpose: Data are limited on the long-term efficacy and safety of drug-coated balloon (DCB) treatment in comparison to drug-eluting stent (DES) for de novo coronary lesions. We investigated the long-term clinical outcomes of DCB treatment in percutaneous coronary intervention (PCI) for de novo coronary lesions., Materials and Methods: A total of 103 patients scheduled for elective PCI for de novo non-small coronary lesions (≥2.5 mm) who were successfully treated with DCB alone were retrospectively compared with 103 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n=13160). All patients were followed for 5 years. The primary endpoint was major adverse cardiac events [MACE; cardiac death, myocardial infarction, stroke, target lesion thrombosis, target vessel revascularization (TVR), and major bleeding] at 5 years., Results: At 5-year clinical follow-up, Kaplan-Meier estimates of the rate of MACE were significantly lower in the DCB group [2.9% vs. 10.7%; hazard ratio (HR): 0.26; 95% confidence interval (CI): 0.07-0.96; log-rank p =0.027]. There was a significantly lower incidence of TVR in the DCB group (1.0% vs. 7.8%; HR: 0.12; 95% CI: 0.01-0.98; long-rank p =0.015), and there was major bleeding only in the DES group (0.0% vs. 1.9%; log-rank p =0.156)., Conclusion: At 5-year follow-up, DCB treatment was significantly associated with reduced incidences of MACE and TVR, compared with DES implantation, for de novo coronary lesions., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Background:  High-sensitivity C-reactive protein (hs-CRP) has been proposed as an indicator of inflammation and cardiovascular risk. However, little is known of the comparative temporal profile of hs-CRP and its relation to outcomes according to the disease acuity., Methods:  We enrolled 4,263 East Asian patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and stable disease. hs-CRP was measured at baseline and 1 month post-PCI. Major adverse cardiovascular events (MACE: the composite occurrence of death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years., Result:  The AMI group ( n  = 2,376; 55.7%) had higher hs-CRP baseline than the non-AMI group ( n  = 1,887; 44.3%) (median: 1.5 vs. 1.0 mg/L; p  < 0.001), which remained higher at 1 month post-PCI (median: 1.0 vs. 0.9 mg/L; p  = 0.001). During 1 month, a high inflammatory-risk phenotype (upper tertile: hs-CRP baseline ≥ 2.4 mg/L) was associated with a greater MACE in the AMI group (adjusted hazard ratio [HR adj ]: 7.66; 95% confidence interval [CI]: 2.29-25.59; p  < 0.001), but not in the non-AMI group (HR adj : 0.74; 95% CI: 0.12-4.40; p  = 0.736). Between 1 month and 4 years, a high inflammatory-risk phenotype (upper tertile: hs-CRP 1 month ≥ 1.6 mg/L) was associated with greater MACE compared to the other phenotype in both the AMI (HR adj : 2.40; 95% CI: 1.73-3.45; p  < 0.001) and non-AMI groups (HR adj : 2.67; 95% CI: 1.80-3.94; p  < 0.001)., Conclusion:  AMI patients have greater inflammation during the early and late phases than non-AMI patients. Risk phenotype of hs-CRP baseline correlates with 1-month outcomes only in AMI patients. However, the prognostic implications of this risk phenotype appears similar during the late phase, irrespective of the disease acuity., Competing Interests: P.A.G. has received grants and personal fees from Bayer HealthCare, Otitopic, Amgen, Janssen, and US WorldMeds; grants from Instrumentation Laboratory, Hikari Dx, Haemonetics, Medicure, and Idorsia Pharmaceuticals; personal fees from UpToDate; and has patents “Detection of Restenosis Risk in Patients Issued” and “Assessment of Cardiac Health and Thrombotic Risk in a Patient.” Y-H. J. has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals, and research grants or support from Yuhan Pharmaceuticals and U and I Corporation. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (Thieme. All rights reserved.)

Background: Data on drug-coated balloon (DCB) treatment in the context of diabetes mellitus (DM) and multivessel coronary artery disease (CAD) are limited. We aimed to investigate the clinical impact of DCB-based revascularization on percutaneous coronary intervention (PCI) in patients with DM and multivessel CAD., Methods: A total of 254 patients with multivessel disease (104 patients with DM) successfully treated with DCB alone or combined with drug-eluting stent (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n = 13,160 patients) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding at 2 years., Results: The DCB-based group was associated with a reduced risk of MACE in patients with DM (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.05-0.68, p = 0.003], but not in those without DM (HR 0.52, 95% CI 0.20-1.38, p = 0.167) at the 2-year follow-up. In patients with DM, the risk of cardiac death was lower in the DCB-based group than the DES-only group, but not in those without DM. In both patients with or without DM, the burdens of DES and small DES (less than 2.5 mm) used were lower in the DCB-based group than in the DES-only group., Conclusions: In multivessel CAD, the clinical benefit of a DCB-based revascularization strategy appears to be more evident in patients with DM than in those without DM after 2 years of follow-up. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277)., (© 2023. The Author(s).)

Aims: Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity., Methods and Results: From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY30): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013-1.036; P < 0.001] and LY30 (per one% increase: OR: 0.934; 95% CI: 0.893-0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of 'MA ≥ 68 mm' and 'LY30 < 0.2%' was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135-2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499-2.129; P = 0.935)., Conclusion: AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI., Clinical Trial Registration: Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529., Competing Interests: Conflict of interest Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and Han-mi Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals, Han-mi Pharmaceuticals, Sam-jin Pharmaceuticals, Biotronik, and U&I Corporation. Dr Gurbel has received grants and personal fees from Bayer HealthCare, Otitopic, Amgen, Janssen, and US WorldMeds; grants from Instrumentation Laboratory, Hikari Dx, Hae monetics, Medicure, and Idorsia Pharmaceuticals; personal fees from UpToDate; and has patents ‘Detection of Restenosis Risk in Patients Issued’ and ‘Assessment of Cardiac Health and Thrombotic Risk in a Patient’. The other authors report no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug-eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all-cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity-adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20-2.12]; women with HPR: HR, 0.99 [95% CI, 0.69-1.42]) and all-cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07-2.44]; women with HPR: HR, 0.92 [95% CI, 0.57-1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE ( P interaction =0.013) or all-cause mortality ( P interaction =0.025). Conclusions In this study, HPR was a differential risk factor for 1-year MACCEs and all-cause mortality in women and men. And it was an independent predictor of 1-year MACCEs and all-cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028.

Background/aims: Bleeding events after percutaneous coronary intervention (PCI) have important prognostic implications. Data on the influence of an abnormal ankle-brachial index (ABI) on both ischemic and bleeding events in patients undergoing PCI are limited., Methods: We included patients who underwent PCI with available ABI data (abnormal ABI, ≤ 0.9 or > 1.4). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, and major bleeding., Results: Among 4,747 patients, an abnormal ABI was observed in 610 patients (12.9%). During follow-up (median, 31 months), the 5-year cumulative incidence of adverse clinical events was higher in the abnormal ABI group than in the normal ABI group: primary endpoint (36.0% vs. 14.5%, log-rank test, p < 0.001); all-cause death (19.4% vs. 5.1%, log-rank test, p < 0.001); MI (6.3% vs. 4.1%, log-rank test, p = 0.013); stroke (6.2% vs. 2.7%, log-rank test, p = 0.001); and major bleeding (8.9% vs. 3.7%, log-rank test, p < 0.001). An abnormal ABI was an independent risk factor for all-cause death (hazard ratio [HR], 3.05; p < 0.001), stroke (HR, 1.79; p = 0.042), and major bleeding (HR, 1.61; p = 0.034)., Conclusion: An abnormal ABI is a risk factor for both ischemic and bleeding events after PCI. Our study findings may be helpful in determining the optimal method for secondary prevention after PCI.

Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians., Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes., Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure., Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HR adj : 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HR adj : 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HR adj : 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HR adj : 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028)., Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events. (Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the Platelet-Thrombosis Research Group under the Korean Society of Intervention Cardiology. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK inno. N Pharmaceuticals, and DIO Medical Ltd. Dr Song has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, Bayer Korea, and Samjin Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Data on drug-coated balloon (DCB) treatment in the context of multivessel coronary artery disease (CAD) are limited., Objectives: The purpose of this study was to investigate the impact of DCB-based treatment on percutaneous coronary intervention for multivessel CAD., Methods: A total of 254 patients with multivessel disease successfully treated with DCBs or in combination with drug-eluting stents (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) registry (n = 13,160) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent thrombosis, target vessel revascularization, and major bleeding at 2 years., Results: Baseline clinical characteristics were comparable between the groups. In the DCB-based group, 34.3% of patients were treated with DCBs only and 65.7% were treated with the DES hybrid approach. The number of stents and total stent length were significantly reduced by 65.4% and 63.7%, respectively, in the DCB-based group compared with the DES-only group. Moreover, the DCB-based group had a lower rate of MACE than the DES-only group (3.9% and 11.0%; P = 0.002) at 2-year follow-up. The DES-only group had a higher risk for cardiac death and major bleeding., Conclusions: The DCB-based treatment approach showed a significantly reduced stent burden for multivessel percutaneous coronary intervention and led to a lower rate of MACE than the DES-only treatment. This study shows that DCB-based treatment approach safely reduces stent burden in multivessel CAD, and improved long-term outcomes may be expected by reducing stent-related events. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term prognostic implication of platelet reactivity after percutaneous coronary intervention (PCI) is not clearly known., Objectives: The impacts of platelet reactivity from the PTRG-DES consortium were assessed., Methods: The primary endpoint was the major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, stent thrombosis, or stroke. Key secondary endpoints were all-cause mortality, major bleeding, and net adverse clinical events (NACE), including MACCE and bleeding., Results: Between 2003 and 2018, a total of 11,714 patients were enrolled and grouped into tertiles according to P2Y 12 reaction units (PRUs): high PRUs (≥253), intermediate PRUs (188-252), and low PRUs (<188). The Kaplan-Meier (KM) estimates of the primary outcome were significantly different across the groups; the high-PRU group showed the highest MACCE rate at 5 years (12.9%, 11.1%, and 7.0% in high-, intermediate-, and low-PRU groups, respectively; P < 0.001), as well as at 1 year (P < 0.001). The high-PRU group had the greatest KM estimates of all-cause death (8.2%, 5.9%, and 3.7%, respectively; P < 0.001) at 5 years without significant differences of major bleeding, and resultant of a higher KM estimates of NACE (15.7%, 13.6%, and 9.7%, respectively; P < 0.001). A PRU ≥252, the best cutoff value, was strongly related to MACCE (HR: 1.39; 95% CI: 1.11-1.74; P = 0.003) and all-cause death at 5 years after PCI (HR: 1.42; 95% CI: 1.04-1.94; P = 0.026). The optimal cutoff value of aspirin reaction units predicting the MACCE occurrence was ≥414 and was significantly associated with 5-year MACCE occurrence or all-cause death (P < 0.001)., Conclusions: In this large-scale cohort, high PRU was significantly associated with occurrence of MACCE, all-death death, and NACE at 5 years, as well as 1 year after PCI. (PTRG-DES Consortium [PTRG]; NCT04734028)., Competing Interests: Funding Support and Author Disclosures The study was designed by the principal investigator and executive committee and was sponsored by the Korean Society of Intervention Cardiology. The funder had no role in study design, data collection, analyses, data interpretation, or preparing the manuscript. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, Sanofi, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and has received research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr Joo has received honoraria for lectures from AstraZeneca, Han-mi Pharmaceuticals, Samjin, Dong-A, HK inno.N Pharmaceuticals, and DIO Medical. Dr Song has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, Sanofi, Bayer Korea, and Samjin Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Abstract: Appropriate risk stratification and timely revascularization of acute myocardial infarction (AMI) are available in percutaneous coronary intervention (PCI) - capable hospitals (PCHs). This study evaluated whether direct admission vs inter-hospital transfer influences cardiac mortality in patients with AMI. This study was conducted in the PCH where the patients were able to arrive within an hour. The inclusion criteria were AMI with a symptom onset time within 24 hours and having undergone PCI within 24 hours after admission. The cumulative incidence of cardiac death after percutaneous coronary intervention was evaluated in the direct admission versus inter-hospital transfer groups. Among the 3178 patients, 2165 (68.1%) were admitted via inter-hospital transfer. Patients with ST-segment elevation myocardial infarction (STEMI) in the direct admission group had a reduced symptom onset-to-balloon time (121 minutes, P < .001). With a median period of 28.4 (interquartile range, 12.0-45.6) months, the cumulative incidence of 2-year cardiac death was lower in the direct admission group (NSTEMI, 9.0% vs 11.0%, P = .136; STEMI, 9.7% vs 13.7%, P = .040; AMI, 9.3% vs 12.3%, P = .014, respectively). After the adjustment for clinical variables, inter-hospital transfer was the determinant of cardiac death (hazard ratio, 1.59; 95% confidence interval, 1.08-2.33; P = .016). Direct PCH admission should be recommended for patients with suspected AMI and could be a target for reducing cardiac mortality., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Patients with peripheral artery disease (PAD) have shown the increased risk of cardiovascular (CV) morbidity and mortality. This study sought to evaluate the impact of clot strength on prevalence and major adverse CV events (MACE) of PAD in high-risk patients. We enrolled patients undergoing percutaneous coronary intervention (PCI) (n = 1667) with available platelet-fibrin clot strength [thrombin-induced maximal amplitude (MA thrombin ) measured by thromboelastography] and inflammation [high sensitivity C-reactive protein (hs-CRP)]. PAD was defined with abnormal ankle-brachial index (≤ 0.9 or > 1.4). MACE was defined as a composite of CV death, myocardial infarction or stroke. PAD was observed in 201 patients (12.1%). In the multivariate analysis, high clot strength [MA thrombin  ≥ 68 mm: odds ratio (OR) 1.70, 95% confidence interval (CI) 1.20 to 2.41, p = 0.003] and enhanced inflammation (hs-CRP ≥ 3.0 mg/L: OR 2.30, 95% CI 1.56 to 3.41, p < 0.001) were associated with PAD occurrence. During the follow-up post-PCI (median, 25 months), MACE was more frequently occurred in patients with vs. without PAD (18.7% vs. 6.4% at 3 years; hazard ratio 1.72, 95% CI 1.03 to 2.87, p = 0.039). Furthermore, combined presence of PAD and high clot strength significantly increased the risk of MACE. In conclusion, this study is the first to show the impact of clot strength on prevalence and clinical outcomes of PAD in coronary artery disease patients undergoing PCI. Whether antithrombotic strategy according to level of this biomarker can improve clinical outcomes in PAD patients deserves the further study.

Objectives: The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans., Background: Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction., Methods: In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro-B-type natriuretic peptide level at 6 months., Results: Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro-B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m 2 ; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m 2 ; p = 0.056) (difference -2.3 ml/m 2 ; 95% confidence interval: -4.8 to 0.2 ml/m 2 ; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m 2 ; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m 2 ; p = 0.366) (difference -1.8 ml/m 2 ; 95% confidence interval: -3.5 to -0.1 ml/m 2 ; p = 0.040)., Conclusions: Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y 12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y 12 -inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention., (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.)

Background: This study aimed to evaluate whether the coronary artery calcium score (CACS) measured with computed tomography coronary angiography (CTCA) predicts periprocedural myocardial infarction (PMI) in patients undergoing an elective percutaneous coronary intervention (PCI)., Patients and Methods: A total of 197 patients with stable angina underwent elective PCI after CTCA. We evaluated CACS using CTCA and assessed the clinical risk factors for PMI. PMI was defined as an elevation of troponin I levels exceeding five times the upper limit of normal within 24 h after PCI. Patients were followed up for major adverse cardiovascular events for a median of 4.6 years., Results: The prevalence of PMI was 18.7% (37 patients) and patients with PMI showed a trend toward a higher CACS (721±779 vs. 498±842, P=0.142). The prevalence of PMI showed a positive correlation with the CACS distribution [8.0%, first interquartile range (IQR); 14.3%, second IQR; 22.4%, third IQR; 30.6%, fourth IQR; P=0.002]. The CACS cut-off value for PMI was greater than 113 (area under the curve: 0.670; 95% confidence interval: 0.600-0.736; P<0.001). Patients with CACS greater than 113 before PCI showed a higher prevalence of PMI (26.2 vs. 5.6%, odds ratio: 5.994; P<0.001). Multivariate analysis showed that CACS greater than 113 was the main predictor for PMI (odds ratio: 3.61, 95% confidence interval: 1.145-11.363; P=0.028). In this study, the cumulative incidence of major adverse cardiovascular event was higher in patients with PMI (54.1 vs. 10.6%; P<0.001)., Conclusion: This study suggests that high CACS measured with CTCA influences the occurrence of PMI, which is associated with worse cardiovascular outcomes.

Background/aims: Although a low triiodothyronine (T3) state is closely associated with heart failure (HF), it is uncertain whether total T3 levels on admission is correlated with the clinical outcomes of acute myocardial infarction (AMI). The aim of this study is to investigate the prognostic value of total T3 levels for major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with AMI undergone percutaneous coronary intervention (PCI)., Methods: A total of 765 PCI-treated AMI patients (65.4 ± 12.6 years old, 215 women) between January 2012 and July 2014 were included and 1-year MACCEs were analyzed. We assessed the correlation of total T3 and free thyroxine (fT4) with prevalence of 1-year MACCEs and the predictive values of total T3, fT4, and the ratio of total T3 to fT4 (T3/fT4), especially for HF requiring re-hospitalization., Results: Thirty patients (3.9%) were re-hospitalized within 12 months to control HF symptoms. Total T3 levels were lower in the HF group than in the non-HF group (84.32 ± 21.04 ng/dL vs. 101.20 ± 20.30 ng/dL, p < 0.001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤ 85 ng/dL) and T3/fT4 (≤ 60) for HF (area under curve [AUC] = 0.734, p < 0.001; AUC = 0.774, p < 0.001, respectively). In multivariate analysis, lower T3/fT4 was an independent predictor for 1-year HF in PCI-treated AMI patients (odds ratio, 1.035; 95% confidential interval, 1.007 to 1.064; p = 0.015)., Conclusions: Lower levels of total T3 were well correlated with 1-year HF in PCI-treated AMI patients. The T3/fT4 levels can be an additional marker to predict HF.

With over 1.5 billion people, East Asians are the most populous race in the world. Health status in this population is an important global issue. In the contemporary trials of antithrombotic treatment, East Asian patients have a lower risk for atherothrombotic diseases (especially, Coronary Artery Disease [CAD]) and a higher risk for bleeding (especially, gastrointestinal bleeding and hemorrhagic stroke). Despite these observations, antithrombotic treatment strategies in East Asian patients are mainly based on the American or European guidelines that are derived from randomized, controlled trials including mostly Caucasians. Despite a low response to clopidogrel, East Asian patients with CAD show a similar or even a lower rate of ischemic event occurrence and higher bleeding risk compared with Caucasian patients. The latter is referred to as the "East Asian Paradox", suggesting a dissimilar therapeutic window for antiplatelet therapy than Caucasians. In addition, different net clinical benefits have been observed between the races with potent P2Y12 inhibitors that may be related to racial differences in pharmacokinetic and pharmacodynamic profiles. Furthermore, there is emerging concern regarding differences between East Asian vs. Western patients in pharmacodynamic and clinical efficacies of anticoagulant agents. We now summarize experimental and clinical evidence of the efficacy and safety of antithrombotic agents in the East Asian population. We suggest the concept of "race-tailored antithrombotic treatment" in CAD patients and/or in patients undergoing percutaneous coronary intervention., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The role of platelet-leukocyte interaction in the infarct myocardium still remains unveiled. We aimed to determine the linkage of platelet activation to post-infarct left ventricular remodelling (LVR) process. REMODELING was a prospective, observational, cohort trial including patients (n = 150) with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Patients were given aspirin plus clopidogrel therapy (600 mg loading and 75 mg daily). Platelet reactivity (PRU: P2Y12 Reaction Units) was assessed with VerifyNow P2Y12 assay on admission. Transthoracic echocardiography was performed on admission and at one-month follow-up. The primary endpoint was the incidence of LVR according to PRU-based quartile distribution. LVR was defined as a relative ≥ 20 % increase in LV end-diastolic volume (LVEDV) between measurements. Adverse LVR was observed in 36 patients (24.0 %). According to PRU quartile, LVR rate was 10.8 % in the first, 23.1 % in the second, 27.0 % in the third, and 35.1 % in the fourth (p = 0.015): the optimal cut-off of PRU was ≥ 248 (area under curve: 0.643; 95 % confidence interval: 0.543 to 0.744; p = 0.010). LVR rate also increased proportionally according to the level of high sensitivity-C reactive protein (hs-CRP) (p = 0.012). In multivariate analysis, the combination of PRU (≥ 248) and hs-CRP (≥ 1.4 mg/l) significantly increased the predictive value for LVR occurrence by about 21-fold. In conclusion, enhanced levels of platelet activation and inflammation determined the incidence of adverse LVR after STEMI. Combining the measurements of these risk factors increased risk discrimination of LVR. The role of intensified antiplatelet or anti-inflammatory therapy in post-infarct LVR process deserves further study.

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG ® ). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, -5 PRU; 90% confidence interval of difference, -23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). "BASE" and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG ® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel-aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.

Background: Effective inhibition of platelet aggregation during PCI in high risk patients with ACS is of utmost importance. The new intravenous short acting P2Y 12 -receptor inhibitor cangrelor is available for use in PCI-treated patients. We aimed to study platelet inhibition during treatment with cangrelor and transition phase with oral P2Y 12 -receptor inhibitors in patients with acute coronary syndromes (ACS)., Methods: Cangrelor was administered during PCI to 21 P2Y 12 -inhibitor naïve patients with ACS. Patients received a loading dose of ticagrelor at the time of procedure or prasugrel 30min before end of the cangrelor infusion. Platelet inhibition was measured by multiple electrode aggregometry (MEA) and thromboelastography (TEG), before and after PCI, immediately and 2h after stopping the infusion. Platelet inhibition after PCI was compared to a matched cohort of patients treated with oral P2Y 12 -inibitors only., Results: There was a significant reduction of platelet reactivity measured by MEA-ADP from 46.7U to 17.9U and by TEG MA ADP from 43.1mm to 22.0mm before infusion and after PCI respectively (p<0.001). There was also sustained platelet inhibition after stopping of cangrelor infusion and 2h later. Significant higher platelet inhibition was observed at the end of PCI in comparison to control cohort without cangrelor (MEA 17.9U vs. 54.2U, p=0.001)., Conclusion: We demonstrate significantly improved platelet inhibition during PCI in ACS patients treated with cangrelor in comparison to early treatment with potent oral P2Y 12 -inhibitors. Cangrelor should be considered for periprocedural treatment of high risk patients with acute coronary syndrome., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

An increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with Western population. This study was designed to evaluate the relationship of bleeding to platelet function in East Asians undergoing percutaneous coronary intervention (PCI). Patients who had undergone uneventful PCI (n= 301) were prospectively enrolled and bleeding events were evaluated during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet function was measured during hospitalisation and at 30-day follow-up by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. During 30-day follow-up, 29.2 % of patients (n= 88) experienced post-discharge Bleeding Academic Research Consortium (BARC) complications (24.6 % and 7.0 % of BARC type 1 and 2, respectively). Patients presenting with acute myocardial infarction had fewer episodes of type 1 BARC bleeding (odds ratio: 0.41; 95 % confidence interval: 0.22 to 0.76; p= 0.005). The cut-off of low platelet reactivity (LPR) (20 µM ADP-induced platelet aggregation ≤ 46.1 %; platelet reactivity index ≤ 45.1 %) was the independent determinant of type 2 BARC bleeding (odds ratio: 3.55 and 4.44; p= 0.009 and 0.002, respectively). The first 30-day BARC bleeding episodes were associated with an increased rate of subsequent premature DAPT discontinuation during one-year follow-up (4.7 % vs 11.4 %; odds ratio: 2.60; 95 % confidence interval: 1.04 to 6.50; p= 0.035). In conclusion, among East Asians, mild bleeding episodes are common early after PCI and are associated with premature DAPT discontinuation. Type 2 BARC bleeding episodes are associated with LPR cut-offs measured at 30 days post-discharge.

Addition of a potent P2Y12 inhibitor to aspirin is the standard therapy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitor, together with antiplatelet therapy, may be considered as part of initial therapy in NSTE-ACS patients with high-risk features. This study investigated the antiplatelet effect of ticagrelor loading dose (LD) versus tirofiban bolus injection with a post-bolus infusion on top of aspirin among NSTE-ACS patients planned to PCI. NSTE-ACS patients were randomised to receive either ticagrelor (n = 47) or tirofiban (n = 48). Platelet reactivity was assessed by light transmittance aggregometry at 0, 2, 8, and 24 hours (h) after treatment initiation. Primary endpoint was inhibition of platelet aggregation (IPA, 20 µM ADP, final extent) at 2 h after LD therapy, with a non-inferiority margin of 10%. The prevalence of high on-treatment platelet reactivity (HPR) was also compared at 0, 2, 8, and 24 h. The mean difference in IPA between ticagrelor and tirofiban was -9.9% (95% confidence interval: -25.7% to 5.9%) at 2 h, -1.6% (-8.0% to 4.8%) at 8 h, and -3.3% (-18.4% to 12.0%) at 24 h. The prevalence of HPR did not differ between the two groups at any time point (all p values ≥ 0.059), which was almost abolished by 8 h post-LD (< 5%). In conclusion, the antiplatelet effect during the early phase (~2 h) after ticagrelor LD appeared to be relatively strong, but it did not reach that of tirofiban in NSTE-ACS patients.

Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients., (Copyright © 2014 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Adjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: -2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.

Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients.

Clinical experiences have suggested that East Asians show the higher risk of warfarin-related intracranial hemorrhage compared with Westerners. Therefore, different target of the International Normalized Ratio (INR) in East Asians (1.6-2.6) has been proposed and adapted in clinical practice. In terms with antiplatelet therapy, recent evidence has supported the concept of "therapeutic level of platelet reactivity" to balance clinical efficacy and safety in patients undergoing percutaneous coronary intervention (PCI) or those with acute coronary syndrome (ACS). In line with the warfarin experiences, multiple clinical and pharmacodynamic data from East Asians have shown their different therapeutic level of platelet reactivity following PCI or ACS ("East Asian Paradox"). Furthermore, like most cardiovascular drugs, P2Y12 receptor blockers have marked interethnic differences in the pharmacokinetics and pharmacodynamics. The currently performed clinical trials evaluating the clinical efficacy and safety of potent P2Y12 inhibitors mostly don't include enough number of East Asians to draw reliable conclusions. Therefore, dedicated research and guideline(s) for East Asians are required before we can apply Western recommendations for potent P2Y12 inhibitors in East Asian population. It is a time to consider the paradigm shift from "one-guideline-fits-all races" to "race-tailored antiplatelet therapy" in treating ACS patients.

The relationship between thrombin-induced platelet-fibrin clot strength (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MATHROMBIN measured by thrombelastography on HPR and long-term major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients during aspirin and clopidogrel therapy. MATHROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR ≥ 46% measured by conventional aggregometry. Both high MATHROMBIN(≥ 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation (β coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN increased the predictive value for the risk of HPR (odds ratio: 13.89; 95% confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients (12.7%). HPR and high MATHROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to demonstrate that high platelet-fibrin clot strength is an independent determinant of HPR in PCI-treated patients. Combining the measurements of platelet aggregation and platelet-fibrin clot strength may enhance post-PCI risk stratification and deserves further study.

Background and Objectives: The contribution of multiple risk factors to peri-procedural myocardial infarction (PMI) in East Asians remains controversial. To assess the influence of clinical or laboratory covariates on PMI in these patients., Methods: Stable patients (n=341) undergoing elective percutaneous coronary intervention (PCI) were enrolled. Platelet reactivity was measured by conventional aggregometry and VerifyNow. Inflammation markers and lipid profile were determined by standard methods. PMI was defined according to Universal definition (troponin I or CK-MB ≥ 3 times the 99th percentile of the upper reference limit)., Results: PMI (defined by troponin I and CK-MB) occurred in 47 (13.8%) and 30 (8.8%) patients, respectively. There was no significant difference in ADP-induced platelet reactivity between patients with vs. without PMI. Patients with PMI (troponin I) had higher levels of 6 μg/mL collagen-induced platelet aggregation (PA) and VerifyNow 'BASE' compared with those without PMI. The combination of '6 μg/mL collagen-induced PA>40%'+'BASE>318' (odds ratio, 14.08; 95% confidence intervals, 1.68 to 111.11; p=0.015) or 'WBC>6550/mm(3)'+'C-reactive protein>2.3mg/L' (odds ratio, 7.75; 95% confidence intervals, 2.49 to 24.39; p<0.001) was associated with an increased risk of PMI (troponin I). The greatest likelihood ratio was observed when cholesterol, inflammation marker and platelet function were combined together., Conclusion: This is the first study to demonstrate that heightened platelet responsiveness to collagen and thrombin may be a risk factor for myonecrosis in patients undergoing elective PCI. The utility of the combining measures of platelet function, inflammation and cholesterol to enhance risk stratification and thus facilitate personalized therapy deserves further study., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)