Search

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have investigated a 1 to 6-month short dual antiplatelet therapy (S-DAPT) after percutaneous coronary intervention (PCI) with modern drug eluting-stents to reduce bleeding events., Objectives: To investigate cardiovascular outcomes in patients at high bleeding risk (HBR) according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria after PCI with the Synergy bioresorbable-polymer everolimus-eluting stents (EES)., Methods: We applied ARC-HBR criteria in the population of the prospective, single-arm, multicenter POEM (Performance of Bioresorbable Polymer-Coated Everolimus-Eluting Synergy Stent in Patients at HBR Undergoing Percutaneous Coronary Revascularization Followed by 1-Month Dual Antiplatelet Therapy) trial. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 12 months., Results: The original POEM cohort included 356 patients (80.4 %) fulfilling ARC-HBR criteria. Oral anticoagulant (OAC) usage and age ≥75 years were the most frequent major and minor ARC-HBR criteria, respectively. The ARC-HBR group was mainly represented by men (71.1 %), with 74.4 ± 9.3 years and a high burden of cardiovascular risk factors. DAPT was prescribed in 79.3 %, and single antiplatelet (SAPT) with OAC in 18.7 %. 12-month follow-up was completed in 96.2 %. The primary endpoint occurred in 5.2 % (95 % CI 3.29-8.10) of patients, whereas bleeding Academic Research Consortium type 3-5 occurred in 2.7 % (95 % CI, 1.39 %-5.05 %)., Conclusion: Previous results of the POEM trial showed positive outcomes regarding ischemic and bleeding events with an S-DAPT regimen after Synergy EES. These results are also confirmed in sub-group analysis when ARC-HBR criteria are applied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To report procedural and 1-year outcomes following COBRA PzF NCS implantation in a routine daily setting with high bleeding risk (HBR) patients treated with clopidogrel as mono antiplatelet therapy (MAPT)., Methods: This is a prospective, consecutive, observational study in HBR patients who underwent PCI with COBRA PzF NCS and treated with clopidogrel alone at discharge. The primary endpoint was definite stent thrombosis at one month. The secondary endpoint was MACE (Cardiac Death, myocardial infarction (MI), target lesion revascularization (TLR)) at 12 months., Results: From October 2015 to December 2018, 77 patients with 120 lesions were enrolled and treated. Mean age was 78.7 ± 8.89 years, 58.5% men and 18.2% had ACS. Patients included had a minimum of 2.0 inclusion LEADERS FREE criteria. Angiographic success was achieved in all cases. The primary endpoint occurred in 0%, no stent thrombosis was occurred. MACE at 12-months (available for 52 patients) was 3.8% including cardiac death 0%, MI 0% and TLR 3.8%. No severe bleeding events (BARC3-5) or stroke or late stent thrombosis were noted., Conclusion: Clopidogrel as MAPT after COBRA PzF NCS implantation in HBR patients is feasible and an attractive option. One-year follow-up was associated with excellent clinical outcomes and should be confirmed with large randomised study., Condensed Abstract: This is prospective registry of high bleeding risk patients treated with the COBRA PzF NCS and MAPT at discharge. The primary end point demonstrated no stent thrombosis. The rate of major cardiac adverse events (a composite of cardiovascular death, myocardial infarction and target lesion revascularisation) at 1 year was 3.8%. No severe bleeding events, stroke or late stent thrombosis were noted. One-year follow-up was associated with good clinical outcomes and compared favorably with current devices., Competing Interests: Declaration of competing interest LM is consultant for CeloNova BioSciences, Inc. (modest). The other authors have no disclosure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention., Background: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms., Methods: CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment., Results: Detection of LOF alleles resulted in adjustment of P2Y 12 inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups., Conclusions: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study assessed the ability of the dual-antiplatelet therapy (DAPT) score in stratifying ischemic and bleeding risk in a contemporary percutaneous coronary intervention (PCI) population., Background: The DAPT score is recommended by guidelines as a tool to stratify ischemic and bleeding risk. Its utility in contemporary PCI is unknown., Methods: The study studied patients in GLOBAL LEADERS (A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) who were free of major ischemic and bleeding events and adhered to antiplatelet strategy during the first year after PCI. The primary ischemic endpoint was the composite of myocardial infarction or stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5. Outcomes from 12 to 24 months after PCI were compared according to the DAPT score., Results: Of 11,289 patients that were event-free after the first year, 6,882 and 4,407 patients had low (<2) and high (≥2) DAPT scores, respectively. Compared with a low DAPT score, patients with a high DAPT score had a higher rate of the composites of myocardial infarction or stent thrombosis (0.70% vs. 1.55%; p < 0.0001). The rate of Bleeding Academic Research Consortium type 3 or 5 bleeding was 0.54% and 0.30% in the low and high DAPT score groups, respectively (p = 0.058). The effect of ticagrelor versus aspirin monotherapy on primary ischemic and bleeding endpoints during the second year were no different among the 2 groups., Conclusions: The DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. The score did not provide additional value for selection of antiplatelet strategy beyond the first year., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Objectives: The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes., Background: Clopidogrel is the most broadly used platelet P2Y 12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles., Methods: Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel., Results: A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m 2 , chronic kidney disease [glomerular filtration rate <60 ml/min], and diabetes mellitus) and 1 genetic (cytochrome P450 2C19 loss-of-function alleles). The C-statistics for the score as an integer variable were 0.71 (95% confidence interval [CI]: 0.68 to 0.75) and 0.64 (95% CI: 0.60 to 0.67) in the pharmacodynamic derivation and validation cohorts, respectively. A cutoff score ≥10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI: 0.64 to 0.71) for all-cause death and 0.66 (95% CI: 0.63 to 0.69) for the composite of all-cause death, stroke, or myocardial infarction at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or myocardial infarction, both as a continuous variable and by using the cutoff of ≥10. The score did not predict bleeding., Conclusions: The ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y 12 inhibitors other than clopidogrel should be considered., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Anti-thrombotic regimen in patients on long term anticoagulation requiring coronary intervention remains a clinical challenge., Methods: We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (P2Y12 inhibitor and anticoagulant) in patients on long-term anticoagulants after percutaneous coronary intervention (PCI). Major bleeding was the primary outcome., Results: Three observational studies and 3 randomized controlled trials with a total of 6654 patients met our selection criteria. At a mean follow up of 12.5 months major bleeding was lower in dual therapy cohort compared to triple therapy (2.2% vs 5.2%, RR 0.60, 95% CI 0.44-0.81, P = 0.001). No difference was observed between the two groups for major adverse cardiac events (11.8% vs 13.0%, RR 1.03, CI 0.79-1.34, P = 0.85), all-cause mortality (3.9% vs 5.6%, RR 0.94, CI 0.65-1.36, P = 0.76), myocardial infarction (3.7% vs 3.9%, RR 1.12, CI 0.83-1.50, P = 0.47), target vessel revascularization (6.8% vs 7.1%, RR 1.12, CI 0.72-1.74, P = 0.60), thromboembolic events (1.3% vs 1.6%, RR 0.95, CI 0.55-1.64, P = 0.85) and stent thrombosis (1.3% vs 1.4%, RR1.36, CI 0.84-2.21, P = 0.21)., Conclusion: For patients undergoing PCI and requiring long term anticoagulation, a strategy of P2Y12 inhibitor plus anticoagulant confers a benefit of less major bleeding with no difference in major adverse cardiac events, mortality, myocardial infarction, target vessel revascularization, stent thrombosis or thromboembolism compared with triple therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome., Objectives: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI)., Methods: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR., Results: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis., Conclusion: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis., (© 2019 Aix-Marseille University. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc.)

Background and Aims: International guidelines recommend ticagrelor over clopidogrel as preferred antiplatelet agent in patients following coronary stenting. However, no large real-life evidence is available in East Asians in general, and Chinese in particular, with regard to associated clinical outcomes. The present study aimed to assess the early and delayed outcomes after ticagrelor versus clopidogrel in post stenting Chinese patients., Methods: We conducted the pre-specified interim analysis of Comparison Of Efficacy and Safety Between TIcagrelor and Clopidogrel In Chinese (COSTIC), the ongoing prospective, observational, single-center trial. Primary outcomes include first occurrence of myocardial infarction, stroke, vascular death and Bleeding Academic Research Consortium (BARC) scale bleeding event. Propensity score matching (PSM) was carried out to adjust for differences in baseline characteristics between treatment arms., Results: In total, 4,465 patients were enrolled. After PSM, the patients prescribed with ticagrelor had a lower incidence of primary efficacy endpoint relative to those with clopidogrel (0.6% vs. 1.4%, HR = 0.44, 95%CI: 0.22-0.89, p = 0.019) at 1 month, but similar at 7 days, 6 months and 12 months. Further analysis indicated that the difference only exists in the subgroup of acute myocardial infarction (AMI) patients. With regard to safety, ticagrelor consistently increased the risk of BARC type 2 bleeding compared to clopidogrel at 1 month, 6 months and 12 months., Conclusions: These preliminary data indicate that ticagrelor is superior to clopidogrel with regard to major vascular thrombotic outcomes at 1 month, especially in the AMI population, but both groups are similar at 7 days, 6 months and 12 months. Ticagrelor consistently caused significantly more BARC type 2 bleeding., (Copyright © 2019 Elsevier B.V. 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 and Aims: More potent antithrombotic strategies have significantly reduced the rate of recurrent ischemic events in cardiovascular disease. Ticagrelor, in particular, has significantly improved the outcome in patients with acute coronary syndromes, offering potential benefits also in terms of survival. In addition, more recent data have suggested that the advantages of ticagrelor could be extended also to non-coronary atherothrombotic disease, although with contrasting results, especially for mortality reduction. The aim of the present meta-analysis was to investigate the safety and effectiveness of a newer antiplatelet strategy with ticagrelor as compared to traditional antiplatelet regimens in patients with coronary or non-coronary atherothrombotic disease., Methods: Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs. different antiplatelet agents in the secondary prevention of cardiac, cerebral or vascular atherothrombotic events. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stroke., Results: We included 10 randomized clinical trials, for a total population of 73,121 patients, 54.9% randomized to ticagrelor. At a mean follow-up of 13.4 ± 12.6 months, a newer antiplatelet strategy based on ticagrelor was associated with a significant reduction in mortality as compared to a traditional therapy (OR[95%CI] = 0.92[0.86,0.99], p=0.02; phet = 0.14), however, such benefits were more evident in patients with coronary artery disease, while not in non-coronary trials, with a significant interaction between patients' setting and the prognostic impact of ticagrelor (p int = 0.03). A similar result was achieved for cardiovascular mortality, recurrent myocardial infarction, while for the risk of stroke, the largest advantages were observed in patients with a previous cerebrovascular accident. Major bleeding events were increased in ticagrelor treated patients (OR [95%CI] = 1.11 [1.02, 1.20], p=0.01; phet = 0.0003), although not affecting overall mortality, as confirmed by meta-regression analysis., Conclusions: Based on the current meta-analysis, a newer antiplatelet strategy based on ticagrelor is associated with a significant reduction in mortality and recurrent cardiovascular events, as compared to a traditional treatment, among patients treated for coronary disease but not among those with non-coronary atherothrombotic disease. However, ticagrelor therapy was associated with a significant increase in major bleeding complications., (Copyright © 2019. Published by Elsevier B.V.)

Background: Fractional flow reserve (FFR) is used to assess the functional significance of coronary artery stenoses. The optimal anti-thrombotic regimen for FFR has not been studied., Purpose: The goal of this study was to determine whether FFR could be safely performed in Type A coronary lesions, using only upstream dual anti-platelet therapy (DAT) with aspirin and clopidogrel, compared with DAT plus anticoagulation in low risk coronary lesions., Methods/materials: Two hundred patients undergoing FFR for Type A intermediate coronary lesions were blindly randomized into two groups of 100 patients each. Group 1: Upstream DAT, without intra-procedural anti-coagulation and Group 2: Upstream DAT plus intra-procedural bivalirudin. The primary end-points were any coronary thrombotic complications during the index hospital stay, and a composite end-point of any major adverse cardiovascular events (MACE) at 30-days. Secondary end-points included post-procedure troponin levels and TIMI major and minor bleeding scores., Results: There were no thrombotic complications reported. At 30-days, two MACE occurred in Group 1, and three in Group 2 (p=0.83). No difference was seen in the post-procedure troponin levels (p=0.72), or TIMI bleeding scores study between groups (p=093)., Conclusions: This initial study evaluating a simplified anti-thrombotic regimen for FFR, suggests that FFR can be performed in low risk coronary lesions using DAT without the need for intra-procedural anticoagulation, with similar results as DAT plus anticoagulation with bivalirudin. Further research in this area is needed to determine the optimal and most cost-effective anti-thrombotic regimen for FFR calculation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Perioperative management of antithrombotic therapy in patients treated with coronary stents undergoing surgery remains poorly defined. Importantly, surgery represents a common reason for premature treatment discontinuation, which is associated with an increased risk in mortality and major adverse cardiac events. However, maintaining antithrombotic therapy to minimize the incidence of perioperative ischemic complications may increase the risk of bleeding complications. Although guidelines provide some recommendations with respect to the perioperative management of antithrombotic therapy, these have been largely developed according to the thrombotic risk of the patient and a definition of the hemorrhagic risk specific to each surgical procedure, key to defining the trade-off between ischemia and bleeding, is not provided. These observations underscore the need for a multidisciplinary collaboration among cardiologists, anesthesiologists, hematologists and surgeons to reach this goal. The present document is an update on practical recommendations for standardizing management of antithrombotic therapy management in patients treated with coronary stents (Surgery After Stenting 2) in various types of surgery according to the predicted individual risk of thrombotic complications against the anticipated risk of surgical bleeding complications. Cardiologists defined the thrombotic risk using a "combined ischemic risk" approach, while surgeons classified surgeries according to their inherent hemorrhagic risk. Finally, a multidisciplinary agreement on the most appropriate antithrombotic treatment regimen in the perioperative phase was reached for each surgical procedure., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type., Methods: PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type., Results: The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281)., Conclusions: Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: High platelet reactivity (HPR) was studied in patients presenting with ST-segment elevation myocardial infarction (STEMI) due to stent thrombosis (ST) undergoing immediate percutaneous coronary intervention (PCI)., Background: HPR on P2Y 12 inhibitors (HPR-ADP) is frequently observed in stable patients who have experienced ST. The HPR rates in patients presenting with ST for immediate PCI are unknown., Methods: Consecutive patients presenting with definite ST were included in a multicenter ST registry. Platelet reactivity was measured before immediate PCI with the VerifyNow P2Y 12 or Aspirin assay., Results: Platelet reactivity was measured in 129 ST patients presenting with STEMI undergoing immediate PCI. HPR-ADP was observed in 76% of the patients, and HPR on aspirin (HPR-AA) was observed in 13% of the patients. HPR rates were similar in patients who were on maintenance P2Y 12 inhibitor or aspirin since stent placement versus those without these medications. In addition, HPR-ADP was similar in patients loaded with a P2Y 12 inhibitor shortly before immediate PCI versus those who were not. In contrast, HPR-AA trended to be lower in patients loaded with aspirin as compared with those not loaded., Conclusions: Approximately 3 out of 4 ST patients with STEMI undergoing immediate PCI had HPR-ADP, and 13% had HPR-AA. Whether patients were on maintenance antiplatelet therapy while developing ST or loaded with P2Y 12 inhibitors shortly before undergoing immediate PCI had no influence on the HPR rates. This raises concerns that the majority of patients with ST have suboptimal platelet inhibition undergoing immediate PCI., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

To evaluate the efficacy and safety of long-duration dual antiplatelet therapy (L-DAPT) compared to short-duration dual antiplatelet therapy (S-DAPT) after drug-eluting stent implantation. We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials assessing the clinical effect of L-DAPT vs S-DAPT after drug-eluting stent. Efficacy end points were all-cause mortality, cardiac mortality, myocardial infarction (MI), stent thrombosis (ST), and target vessel revascularization (TVR). Safety end points were TIMI major bleeding and stroke. Event rates were compared using a random-effects model. We identified 11 randomized controlled trials in which 33,520 patients were randomized to S-DAPT (N = 16,687) and L-DAPT (n = 16,833), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of TIMI major bleeding (1.40 [1.08-1.81] and 0.60 [0.41-0.89], respectively), without any significant differences in the rate of all-cause mortality, cardiac mortality, ST, TVR, and stroke (0.88 [0.75-1.04], 0.98 [0.79-1.22], 1.54 [0.95-2.50], 0.99 [0.73-1.34], and 1.01 [0.78-1.32], respectively). Our results showed that compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all-cause mortality, cardiac mortality, ST, TVR, and stroke., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Previous reports have been inconsistent in generating a consensus for optimal treatment strategy for patients with percutaneous coronary intervention (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and network meta-analysis to evaluate the safety and efficacy of anti-thrombotic regimens in this subset of patients., Methods: 30 articles were recovered through preferred reporting items for systematic reviews and meta-analyses (PRISMA) using MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) from inception to December 2016., Results: Dual antiplatelet therapy (DAPT) was found to be the safest treatment modality when compared to triple therapy (TT) or combination of OAC and single antiplatelet agent (OAC+SAP) [Major bleeding: (DAPT vs OAC+SAP: odds ratio (OR), 0.53; 95% credible interval (CrI), 0.30-0.91) (DAPT vs TT: OR, 0.45; 95% CrI, 0.31-0.64)]. There were no significant differences in major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular (CV) or total survival, stent thrombosis or target vessel revascularization (TVR) amongst the three treatment arms. TT was ranked superior for stroke reduction (SUCRA, 69%) followed by OAC+SAP and DAPT. When traditional analysis was adjusted for randomized data, OAC+SAP was equivalent to TT with regards to stroke (OR, 0.74; 95% confidence interval (CI), 0.38-1.46; p=0.39) and showed significant reduction in MACE and total mortality., Conclusion: DAPT was found to be the safest and equally effective regimen when compared to TT and OAC+SAP. However this strategy bears considerable risk to patients with high thromboembolic risk. This issue can be encountered by using OAC+SAP as an alternative of TT in patients with intermediate to high stroke risk and intermediate to high bleeding propensity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The introduction of bioresorbable vascular scaffolds (BVS) for clinical use has raised a number of questions on whether current dual-antiplatelet therapy (DAPT) recommendations after drug-eluting stent (DES) implantation, mostly deriving from data on second-generation DES, are also applicable to this completely different technology. This article aims to review the technical shortcomings of BVS-the most extensively studied fully bioresorbable coronary stent-and its contemporary rates of scaffold thrombosis, with a focus on recommendations for DAPT duration., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to describe temporal trends and determine the comparative effectiveness of bivalirudin versus unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI)., Background: Several clinical trials have compared the safety and effectiveness of bivalirudin versus UFH during PCI for STEMI, but results have been conflicting., Methods: Trends in anticoagulant use were examined among 513,775 PCIs for STEMI from July 2009 through December 2014 within the National Cardiovascular Data Registry CathPCI Registry. We conducted an instrumental variable analysis comparing bivalirudin with UFH, using operator preference for bivalirudin as the instrument. We used a test of mediation to determine the extent to which differences in outcomes between anticoagulants were due to differences in use of glycoprotein IIb/IIIa inhibitors (GPI). Primary outcomes were in-hospital bleeding and mortality., Results: Bivalirudin use increased from 2009 through 2013, followed by a new decline. GPIs were used in 74.7% of UFH PCIs versus 26.5% of bivalirudin PCIs. In unadjusted analyses, bivalirudin was associated with decreased bleeding (risk difference [RD]: -4.2%; p < 0.001) and mortality (RD: -0.84%; p < 0.001). After instrumental variable analyses, bivalirudin remained associated with less bleeding (RD: -3.75%; p < 0.001), but not mortality (RD: -0.10%; p = 0.280). The higher rate of GPI use with UFH was responsible for more than one-half of bivalrudin's bleeding reduction (GPI-adjusted RD: -1.57%; p < 0.001). Bleeding reductions were negligible for transradial PCI (RD: -0.11%; p = 0.842)., Conclusions: The use of bivalirudin during STEMI has decreased. Bivalirudin was associated with reduced bleeding and no mortality difference. The bleeding reduction with bivalirudin was largely explained by the greater use of GPIs with UFH., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI)., Methods: MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia., Results: A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding., Conclusions: Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding., (Copyright © 2016. Published by Elsevier Inc.)

Objective: We aimed to investigate the association between platelet-leukocyte aggregates (PLA) levels on admission and the risk of myocardial no-reflow in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI)., Methods: A total of 83 patients with STEMI undergoing primary PCI were included in the current study. Platelet-leukocyte conjugates (PLA), including platelet-monocyte aggregates (PMA), platelet-neutrophil aggregates (PNA) and platelet-lymphocyte aggregates were studied by flow cytometry in peripheral venous blood. No-reflow was defined as coronary blood flow grade thrombolysis in myocardial infarction ≤2 or thrombolysis in myocardial infarction 3 and myocardial blush grade ≤2., Results: No-reflow was observed in 19 patients (22.9%). Compared with the reflow group, the level of PNA (76.5 ± 13.3) and PMA (90.3 ± 5.2) before PCI no-reflow group was significantly higher than that in normal reflow (P < 0.001). Using multiple logistic regression analysis, PNA (odds ratio [OR] = 1.179; 95% CI: 1.035-1.342; P = 0.013) and PMA (OR = 1.248; 95% CI: 1.040-1.498; P = 0.017) were found to be a significant predictor of no-reflow together with pain to balloon time (OR = 1.022; 95% CI: 1.002-1.041; P = 0.028), estimated glomerular filtration rate (OR = 1.311; 95% CI: 1.009-1.856; P = 0.047) and higher thrombus burden (OR = 0.061; 95% CI: 0.006-0.658; P = 0.021). Receiver operating characteristic curve analysis revealed that PNA (area under the curve = 0.881; 95% CI: 0.809-0.952; P < 0.001), PMA (area under the curve = 0.794; 95% CI: 0.699-0.889; P < 0.001) have important predictive value for the myocardial no-reflow., Conclusions: Our study indicated that preprocedural increased PLA levels display a significantly independent association with no-reflow phenomenon after PCI. Increased PLA levels may predict the development of no-reflow phenomenon in patients with STEMI who underwent PCI., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the efficacy of various doses of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion to prevent acute stent thrombosis (AST)., Background: In several recent randomized controlled trials, bivalirudin infusion was continued post-PCI as either a full PCI dose (Biv-Full) or a reduced dose (Biv-Low) to reduce the risk for AST. The results of these trials varied, so the authors performed a meta-analysis of RCTs to determine whether the risk for AST is dose dependent., Methods: Scientific databases and Web sites were searched for RCTs. A traditional meta-analysis was performed using moderator analyses and network meta-analysis using mixed-treatment comparison models to compare the efficacy of various bivalirudin doses in reducing AST., Results: Data from 5 trials including 16,294 patients were analyzed. Compared with heparin, bivalirudin increased AST risk 2-fold, but this was ameliorated by continuing Biv-Full (risk ratio: 0.90, 95% confidence interval: 0.32 to 2.54; p = 0.852). This effect was not seen with Biv-Low. Similarly, in mixed-treatment models, no difference in AST rate was found between heparin and Biv-Full (odds ratio: 0.97; 95% confidence interval: 0.36 to 2.21). After 30 days, bivalirudin decreased the risk for major bleeding by 47% compared with heparin; this benefit persisted even with continued Biv-Full post-PCI (risk ratio: 0.29; 95% confidence interval: 0.16 to 0.53; p < 0.001)., Conclusions: Although bivalirudin is associated with a greater risk for AST than heparin post-primary PCI, this limitation may be mitigated by continuing Biv-Full (not Biv-Low) 3 to 4 h post-operatively. The decrease in bleeding risk with bivalirudin compared with heparin is not compromised by this strategy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background/purpose: The clinical performance of bioresrobable scaffolds (BRSs) in bifurcation lesion is not well investigated so far and information can currently mostly be gleaned from the results of bench testing. The present analysis evaluates the technical feasibility of BRS use in this type of lesion and its mid-term clinical outcome., Methods/materials: Consecutive patients with bifurcation lesions treated with at least one everolimus-eluting BRS were enrolled. Procedural success was defined as successful delivery and deployment of at least one BRS and a residual diameter stenosis ≤30%. The primary endpoint (major adverse cardiac events, MACE) included death due to cardiac cause, clinically driven percutaneous or surgical target lesion revascularization (TLR), and any myocardial infarction at the 12-month follow-up., Results: A total of 28 patients were eligible for this evaluation. Median age was 67 (52-73) years and in 46.4% (13/28) an acute coronary syndrome was present. The procedural success rate was 97.1% (33/34). The 1-year Kaplan Meier event rates for MACE, target lesion revascularization, and scaffold thrombosis were 16.1%, 12.1%, and 8.1%, respectively. Half of these patients discontinued the antiplatelet therapy prematurely., Conclusions: The results for BRS use in bifurcation lesions are not in line with previous studies investigating primarily simple lesions. The impaired outcomes are most likely related to the early stage of BRS use and an exacerbated risk of scaffold thrombosis due to premature discontinuation of the antiplatelet therapy. Hypothesis generated from this investigation has to be proven in further studies., Summary: Technical feasibility of everolimus-eluting bioresorbable scaffold implantation in bifurcation lesion and the clinical mid-term outcomes were evaluated in a real world scenario. Technical success rate was high; however the clinical results were not in line with previous studies investigating primarily simple lesions. The impaired outcomes were mostly driven by an exacerbated risk of scaffold thrombosis due to premature discontinuation of the antiplatelet therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS., Background: To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS)., Methods: Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year., Results: A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization., Conclusions: Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This registry evaluated the safety and clinical outcomes of the Combo stent in an all-comers population in routine clinical practice. We report 1-year results., Background: Limitations of current generation drug-eluting stents (DES) are 3-fold: stent thrombosis, neoatherosclerosis related to impaired healing, and repeat revascularization due to (late-) in-stent restenosis. The Combo stent combines an abluminal biodegradable coating eluting sirolimus and a luminal anti-CD34(+) antibody layer to attract endothelial progenitor cells in order to promote vessel healing, thus preventing neointima formation and restenosis., Methods: The REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) post-market registry was an international, multicenter, prospective trial that evaluated clinical outcomes after deployment of the Combo stent, in an all-comers population of patients treated with a Combo stent in the setting of routine clinical care. Clinical endpoints were target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR)., Results: Between June 2013 and March 2014, a total of 1,000 patients were included in the registry, 49.9% of whom presented with acute coronary syndrome. Mean age was 65 ± 11 years old (range: 34 to 94 years of age), and 74% of patients were male; 58.9% of 1,255 lesions were American Heart Association type B2 or C lesions. The primary endpoints were 5.7% TLF, 1.7% cardiac death, 0.7% target vessel MI, and 4.4% TLR. Definite stent thrombosis occurred in 0.5% of subjects; no thrombosis occurred after 9 days post-stenting., Conclusions: This registry showed excellent 1-year results of novel Combo bioengineered stent technology in an all-comers patient population. (Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE]; NCT01874002)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI)., Background: Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI., Methods: Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods., Results: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor., Conclusions: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study., Background: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min)., Methods: The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h., Results: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events., Conclusions: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580])., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to compare the 1-year outcomes of the ABSORB everolimus-eluting bioresorbable scaffold (BRS) (Abbott Vascular, Santa Clara, California) and the XIENCE everolimus-eluting stent (EES) (Abbott Vascular) in patients undergoing percutaneous coronary intervention., Background: Randomized studies of the ABSORB BRS have been performed in selected patient and lesion scenarios. The available registries of the ABSORB BRS reflect real-world practice more closely compared with randomized studies, but most of them are limited by the small sample size and the lack of comparative outcomes versus second-generation drug-eluting stents., Methods: A total of 1,189 consecutive patients treated with ABSORB BRS from the GHOST-EU (Gauging coronary Healing with bioresorbable Scaffolding plaTforms in EUrope) registry and 5,034 patients treated with XIENCE EES from the XIENCE V USA registry were analyzed. Clinical outcomes were compared with the use of propensity-score matching techniques and reported as Kaplan-Meier estimates and absolute risk difference (D) with 95% confidence intervals (CIs). The primary endpoint was a device-oriented composite endpoint, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization at 1-year follow-up., Results: After propensity score matching was performed for the entire population (N = 6,223), there were 905 matched pairs of patients. In the matched cohort (N = 1,810), there was no significant difference between ABSORB BRS and XIENCE EES in the risk of device-oriented composite endpoint at 1 year (5.8% vs. 7.6%, D = -1.8 [95% CI: -4.1 to 0.5]; p = 0.12). Cardiac death was less likely to occur in the ABSORB BRS group (0.7% vs. 1.9%, D = -1.2 [95% CI: -2.2 to 0.2]; p = 0.03), and a trend toward a reduction in myocardial infarction was noted with ABSORB BRS compared with XIENCE EES (2.4% vs. 4.0%, D = -1.6 [95% CI: -3.2 to 0.0]; p = 0.07). Conversely, no differences in ischemia-driven target lesion revascularization (4.6% vs. 3.5%, D = 1.1 [95% CI: -0.7 to 2.9]; p = 0.22) and definite or probable device thrombosis (1.8% vs. 1.1%, D = 0.7 [95% CI: -0.4 to 1.8]; p = 0.23) were detected between ABSORB BRS and XIENCE EES., Conclusions: In a contemporary large cohort of patients undergoing percutaneous coronary intervention with ABSORB BRS, the combined rate of ischemic events at 1 year was low and nonsignificantly different compared with matched patients treated with XIENCE EES., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to characterize outcomes for everolimus-eluting stent (EES)-treated subjects according to treatment with continued thienopyridine plus aspirin versus aspirin alone 12 to 30 months after stenting., Background: In the DAPT (Dual Antiplatelet Therapy) study, continued thienopyridine plus aspirin beyond 1 year after coronary stenting reduced ischemic events. Given low rates of stent thrombosis and myocardial infarction (MI) for current drug-eluting stents, we examined outcomes among EES-treated subjects in the DAPT study., Methods: The DAPT study enrolled 25,682 subjects (11,308 EES-treated) after coronary stenting. Following 12 months of treatment with thienopyridine and aspirin, eligible subjects continued treatment with aspirin and 9,961 (4,703 with EES) were randomized to 18 months of continued thienopyridine or placebo. Stent type was not randomized, and the EES subset analysis was post hoc., Results: Among EES-treated patients, continued thienopyridine reduced stent thrombosis (0.3% vs. 0.7%, hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.15 to 0.97; p = 0.04) and MI (2.1% vs. 3.2%, HR: 0.63, 95% CI: 0.44 to 0.91; p = 0.01) versus placebo but did not reduce a composite of death, MI, and stroke (4.3% vs. 4.5%, HR: 0.89, 95% CI: 0.67 to 1.18; p = 0.42), and increased moderate/severe bleeding (2.5% vs. 1.3%, HR: 1.79, 95% CI: 1.15 to 2.80; p = 0.01), and death (2.2% vs. 1.1%, HR: 1.80, 95% CI: 1.11 to 2.92; p = 0.02). Death due to cancer and not related to bleeding was increased (0.64% vs. 0.17%; p = 0.01)., Conclusions: In EES-treated subjects, significant reductions in stent thrombosis and MI and an increase in bleeding were observed with continued thienopyridine beyond 1 year compared with aspirin alone. (The Dual Antiplatelet Therapy Study [DAPT Study]); NCT00977938)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied., Methods: Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of ≥1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30days and up to 1year., Results: The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57-2.21, p=0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59-1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01-7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes., Conclusion: The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation., Background: Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes., Methods: In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU)., Results: The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality., Conclusions: In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders., Background: Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome., Methods: The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study., Results: We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036)., Conclusions: Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS., Background: Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES., Methods: Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months., Results: Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001)., Conclusions: DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The need to combine anticoagulant and antiplatelet therapy ('triple therapy') in patients with atrial fibrillation and coronary artery disease increases the risk of bleeding. As percutaneous intervention is now the dominant therapy for coronary disease, clinicians question how to manage the risk of stroke in patients with atrial fibrillation and a coronary stent that require dual antiplatelet therapy. In this review, the risk of stroke and coronary thrombosis in this difficult group of patients will be summarized using current recommendations and guidelines. The scarce randomized data on triple therapy are reviewed, and there will be a focus on currently running trials on this topic., (© 2015 International Society on Thrombosis and Haemostasis.)

Background: There are limited data about long-term outcomes for biodegradable polymer biolimus-eluting stent (BES) versus durable polymer everolimus-eluting stent (EES) in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We sought to compare the two-year efficacy and safety of BES versus EES in AMI patients., Methods: A total of 707 consecutive patients with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction who underwent PCI with BES (n=171) or EES (n=536) between July 2008 and June 2012 were enrolled in this study. The efficacy endpoint (target vessel failure; a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization) and the safety endpoint (a composite of all cause death, myocardial infarction, and stent thrombosis) at two years were compared in crude and propensity score-matched cohorts., Results: After two years, target vessel failure occurred in 13 patients treated with BES and 49 patients treated with EES (7.6% versus 9.1%; adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.58-2.04; p=0.78). The rates of composite safety endpoint at two years were not different between two groups (BES 7.6% versus EES 10.8%; adjusted HR, 0.87; 95% CI, 0.47-1.62; p=0.66). The rates of stent thrombosis did not differ between two groups (BES 0.6% versus EES 1.3%; adjusted HR, 0.63; 95% CI, 0.06-6.20; p=0.69). These findings were substantiated by similar results in the propensity score-matched cohort., Conclusions: In the treatment of patients with AMI, BES showed similar efficacy and safety compared to those of EES for up to two years., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)