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Introduction: An increasing number of patients attending coronary artery bypass grafting (CABG) receive preoperative antiplatelet drugs (acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor). The optimal assessment of preoperative platelet function is the aim of this study for a shorter surgical timing in patients undergoing elective coronary artery bypass grafting., Methods: This study was performed on patients presenting for first-time isolated CABG on therapy with an P2Y12 receptor blockers loading dose (clopidogrel [300 mg] or prasugrel [60 mg] or ticagrelor [180 mg]) or P2Y12 receptor blockers maintenance therapy at least for five days (clopidogrel [75 mg once daily], prasugrel [10 mg once daily], ticagrelor [90 mg twice daily]). All patients received simultaneously acetylsalicylate acid (100 mg daily). Exclusion criterion was emergency CABG regardless of preoperative antiplatelet and anticoagulant therapy. All patients' data were recorded in an Excel® file and analyzed using RStudio® software., Results: Forty-eight consecutive adult patients presenting for CABG were enrolled. Preoperative thromboelastography-platelet mapping showed platelet resistance to P2Y12 blockers receptor - 25% for clopidogrel (6/24), 33% for ticagrelor (6/18), 33% for prasugrel (2/6), and this data was useful to obtain a shorter CABG waiting time in comparison with current guidelines (2.7 vs. five days for clopidogrel, 2.5 vs. five days for ticagrelor, 3.3 vs. seven days for prasugrel)., Conclusion: Preoperative thromboelastography-platelet mapping is helpful to detect harmful P2Y12 receptor blockers resistance and to minimize CABG waiting time avoiding unnecessary and life-threatening delays.

Background: The P2Y12 receptor inhibitors clopidogrel and prasugrel are widely used. Clopidogrel and prasugrel have different metabolic pathways, but whether their adverse event (AE) profiles differ significantly is unclear., Objective: This study aimed to compare the possible AEs induced by clopidogrel and prasugrel and to assess the rank-order of their AEs submitted to a spontaneous reporting database., Materials and Methods: Data were extracted from the Japanese Adverse Drug Event Report database (JADER). Reports of AEs associated with clopidogrel and prasugrel were analyzed to calculate the reporting odds ratios (RORs) and 95% confidence intervals (CIs)., Results: Based on 5869 reports for clopidogrel (69.6%, men) and 513 reports for prasugrel (74.1%, men), 703 and 135 different AEs were identified, respectively. Bleeding complications including hemorrhage were commonly reported for both clopidogrel and prasugrel. As for AEs related to clopidogrel, unexpected AEs such as interstitial lung disease (227 reports; ROR, 1.77; 95% CI, 1.49-2.10), abnormal hepatic function (137 reports; ROR, 1.27; 95% CI, 1.07-1.51), and hepatocellular injury (96 reports; ROR, 120.0; 95% CI, 94.9-151.8) ranked at relatively high positions based on the number of occurrences, unlike prasugrel., Conclusion: This analysis of the national pharmacovigilance database highlights distinct AE profiles for clopidogrel and prasugrel. Unexpected AEs associated with clopidogrel were identified, providing valuable insights for clinical monitoring and patient safety., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kozaru et al.)

Background: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated., Methods and Results: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46)., Conclusions: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y 12 inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain., Methods and results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y 12 inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (P non-inferiority <0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types., Conclusions: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y 12 inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Background: Over the past decade, major society guidelines have recommended the use of newer P2Y 12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice., Methods and Results: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y 12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y 12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 ( P <0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, P trend <0.001), after which the trend was stable ( P trend =0.093)., Conclusions: Over a 13-year-period, there has been a significant increase in use of newer P2Y 12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.

Evidence on comparative effectiveness and safety of prasugrel and ticagrelor post-percutaneous transluminal coronary angioplasty is scarce in Indian population. In a 1:1 propensity score-matched cohort with 71 individuals in each group, the incidence of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization was not significantly different in prasugrel and ticagrelor group (7.04% vs 9.86%; absolute difference, 2.8%; HR, 0.65; 95% CI, 0.21-2.1; p = 0.49). There was no significant difference in bleeding (5.63% vs 9.86%; absolute difference, -4.20%; 95% CI, -13.0%-4.5%) and dyspnea (7.04% vs 12.7%; absolute difference, -5.60%; 95% CI, -15.4%-4.1%)., 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 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Introduction: Prasugrel, a potent P2Y 12 receptor inhibitor, is not currently recommended in patients with stroke due to a higher rate of recurrent stroke. Prasugrel was associated with comparable efficacy to clopidogrel in reducing the risk of ischemic stroke in a recent phase III study., Areas Covered: The authors provide an overview of the potential role of prasugrel in the management of ischemic stroke. The authors searched PUBMED, MEDLINE, and clinicaltrials.org and recently presented trials at the conferences for clinical trials of prasugrel therapy in patients with stroke and TIA, and important original investigations are reviewed., Expert Opinion: The recent PRASTRO-trials demonstrated comparable outcomes of lower maintenance dose (3.5 mg daily dose) with clopidogrel in East Asian stroke patients, thus can be a credible option as a P2Y 12 receptor inhibitor. It can also be considered as a credible option in other races and ethnicities and in other clinical situations that may require DAPT, such as intracranial or carotid stenting. Since prasugrel is associated with a superior antiplatelet effect and is not influenced by genetic polymorphisms, there is no need for platelet function or genetic testing. More work is needed to establish the safety and efficacy of low-dose prasugrel plus aspirin in comparison with currently used clopidogrel plus aspirin in non-East Asian populations.

Pharmacological inhibition of the platelet ADP-receptor P2Y 12 is a cornerstone in the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS). Thienopyridines such as clopidogrel and prasugrel exert their antithrombotic effect by means of active metabolites that irreversibly inhibit P2Y 12 . Due to the short half-life of these metabolites, a subpopulation of ADP-responsive platelets will form in between dosing. With increased platelet turnover rate or poor patient compliance, the fraction of ADP-responsive platelets will increase, potentially increasing the risk for new thrombotic events. In contrast, the reversible P2Y 12 inhibition produced by direct-acting ADP blockers such as ticagrelor and cangrelor inhibit the entire platelet population. In this study, we evaluated the impact of these pharmacological differences on thrombus formation in an ex vivo flow chamber model. A customized image analysis pipeline was used for automatized, large-scale identification and tracking of single platelets incorporated into the thrombus, enabling quantitative analysis of the relative contribution of inhibited and uninhibited platelets to thrombus growth and consolidation. Comparative experiments were conducted using the irreversible and reversible P2Y 12 inhibitors prasugrel active metabolite (PAM) and ticagrelor, respectively. Our results show that PAM inhibited thrombus platelet recruitment more gradually than ticagrelor, with a slower onset of inhibition. Further, we show that the presence of a small fraction (<10%) of uninhibited platelets did not abrogate the antithrombotic effect of PAM to any significant extent. Finally, we demonstrate a gradual enrichment of inhibited platelets in the thrombus shell due to selective recruitment of inhibited platelets to the thrombus periphery.

Aims: Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel., Methods: This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ＞30 kg/m 2 , chronic kidney disease, and diabetes) and HHD-GENE (hypertension, hemodialysis, and diabetes) scores to the primary endpoint of major cardiovascular events after discharge, a composite of death, recurrent MI, and ischemic stroke, were evaluated., Results: The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor., Conclusions: Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.

Background: The P2Y 12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel. As treatment switching is a common clinical practice, the assessment of subsequent switching from a clopidogrel loading dose to the first maintenance dose of oral P2Y 12 receptor antagonists is highly relevant. Objectives: Model-based predictions of inhibition of platelet aggregation (IPA) for the drugs triggering pharmacodynamic interactions were to be derived to support clinical guidance on the transition from selatogrel to oral P2Y 12 receptor antagonists. Methods: Scenarios with selatogrel 16 mg administration or placebo followed by a clopidogrel loading dose and, in turn, prasugrel or ticagrelor maintenance doses at different times of administration were studied. Population pharmacokinetic/pharmacodynamic modeling and simulations of different treatment scenarios were used to derive quantitative estimates for IPA over time. Results: Following selatogrel/placebo and a clopidogrel loading dose, maintenance treatment with ticagrelor or a prasugrel loading dose followed by maintenance treatment quickly achieved sustained IPA levels above 80%. Prior to maintenance treatment, a short time span from 18 to 24 h was identified where IPA levels were predicted to be lower with selatogrel than with placebo if clopidogrel was administered 12 h after selatogrel or placebo. Predicted IPA levels reached with placebo alone and a clopidogrel loading dose at 4 h were consistently lower than with selatogrel administration, followed by a clopidogrel loading dose at 12 h. If a clopidogrel loading dose is administered at 12 h, selatogrel maintains higher IPA levels up to 16 h. IPA levels are subsequently lower than on the placebo until the administration of the first maintenance dose. Conclusions: Model-based predictions informed the transition from selatogrel subcutaneous administration to oral P2Y 12 therapy. The application of modeling techniques illustrates the value of employing pharmacokinetic and pharmacodynamic modeling for the simulation of various clinical scenarios of switching therapies.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y 12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y 12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y 12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Introduction: Currently available platelet function assays largely ignore the important characteristics of in vivo thrombus generation, such as flow conditions and shear. The AggreGuide A-100 ADP Assay detects platelet aggregation in whole blood using light scattering under flow conditions., Areas Covered: In this review article, we discuss the limitations of currently available platelet function assays and the technology underlying the AggreGuide A-100 ADP assay. We also discuss the results of the validation assay study., Expert Opinion: By incorporating arterial flow conditions and shear, the AggreGuide assay may be more indicative of in vivo thrombus generation as compared to currently available platelet function assays. As per the United States, Food and Drug administration, the AggreGuide A-100 ADP test has been cleared to assess antiplatelet effects of prasugrel and ticagrelor. The assay results are comparable to widely used VerifyNow PRU assay. The utility of AggreGuide A100-ADP Assay in guiding P2Y12 receptor inhibitor therapy in patients with cardiovascular disease needs to be explored in clinical studies.

Background and Purpose: Prophylactic prasugrel for endovascular treatment of intracranial aneurysms has been introduced and increased, but HTPR (high on-treatment platelet reactivity) or LTPR (low on-treatment platelet reactivity) of prasugrel is not uncommon in clinical circumstances. To investigate the predisposing factors of HTPR and LTPR on prasugrel premedication in the neurointerventional field and to determine its clinical implications., Materials and Methods: Between February 2016 and December 2020, 191 patients treated with coil embolization using prophylactic prasugrel in 234 intracranial aneurysms were the final candidates for this study. Patient and aneurysm characteristics, clinical status, and laboratory study values were carefully reviewed retrospectively. We performed risk factor analyses for HTPR and LTPR on prasugrel., Results: Ultimately, 20 patients (10.5%) had HTPR, and 74 patients (38.7%) were categorized as having LTPR. In multivariable analyses, the factors related to HTPR were BMI (adjusted OR 1.21, 95% CI 1.04-1.41, p = 0.01), history of antithrombotics (adjusted OR 3.79, 95% CI 1.39-10.34, p = 0.01), and hematocrit (adjusted OR 0.91, 95% CI 0.84-0.99, p = 0.03). Low BMI was the only risk factor for LTPR (adjusted OR 0.84, 95% CI 0.76-0.94, p = 0.001)., Conclusion: In the neurointerventional field, high BMI and prior use of antithrombotic agents were related to HTPR, and low BMI was associated with LTPR on prophylactic prasugrel. High hematocrit levels decreased the risk of HTPR. When preparing endovascular treatment for intracranial aneurysms, attention to patients with these clinical features is required to address the possibility of ischemic or bleeding complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS)., Methods and results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis., Conclusions: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

Background: For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated., Methods: Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed., Results: This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24)., Conclusion: Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS., (© 2023 by the Texas Heart® Institute, Houston.)

Aims: Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS., Methods and Results: Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints., Conclusion: In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy., Study Registration Number: This study was registered in the PROSPERO (ID: CRD42021245477)., Competing Interests: Conflict of interest K.W.P. reports speaker fees from Daichi Sankyo, InnoN Pharmaceutical, and DaeWoong Pharmaceutical, outside of the submitted work. All other authors declare no competing interests., (© 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: Potent P2Y 12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear., Aims: We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS., Methods: Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year., Results: Overall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y 12 inhibitor use over the study period (p trend <0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI., Conclusions: Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

Tailoring antiplatelet therapy based on CYP2C19 pharmacogenetic (PGx) testing can improve cardiovascular outcomes and potentially reduce healthcare costs in patients on a P2Y 12 -inhibitor regime with prasugrel or ticagrelor. However, ubiquitous adoption-particularly in an outpatient setting-remains limited. We conducted a proof-of-concept study to evaluate the feasibility of CYP2C19 -guided de-escalation of prasugrel/ticagrelor to clopidogrel through point-of-care (POC) PGx testing in the community pharmacy. Multiple feasibility outcomes were assessed. Overall, 144 patients underwent CYP2C19 PGx testing in 27 community pharmacies. Successful test results were obtained in 142 patients (98.6%). De-escalation to clopidogrel occurred in 19 patients (20%) out of 95 (67%) eligible for therapy de-escalation, which was mainly due to PGx testing not being included in cardiology guidelines. Out of the 119 patients (84%) and 14 pharmacists (100%) surveyed, 109 patients (92%) found the community pharmacy a suitable location for PGx testing, and the majority of pharmacists (86%) thought it has added value. Net costs due to PGx testing were estimated at €43 per patient, which could be reduced by earlier testing and could turn into savings if de-escalation would double to 40%. Although the observed de-escalation rate was low, POC CYP2C19 -guided de-escalation to clopidogrel appears feasible in a community pharmacy setting.

Background and Objectives: To compare the long-term clinical outcomes of dual antiplatelet therapy (DAPT) with clopidogrel and DAPT with ticagrelor or prasugrel in patients with acute myocardial infarction (AMI) who underwent coronary intervention., Methods: Between November 2011 and December 2015, a total of 13,104 patients with AMI were enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Among them, 4,696 patients who received DAPT for more than 24 months were categorized into two groups: the clopidogrel group (n = 4,053) and ticagrelor or prasugrel group (n = 643). Propensity score matching (PSM) was used to reduce the bias due to confounding variables. Following PSM, the impacts of P2Y12 inhibitors on the clinical outcomes in both groups were compared during a 36-month clinical follow-up period., Results: There were no significant differences in clinical outcomes in terms of cardiac death (7.1% vs. 9.7%, p = 0.101), stroke (1.4% vs. 1.0%, p = 0.436), major bleeding (0.5% vs. 0.8%, p = 0.478), major adverse cardiac events (MACE) (21.6% vs. 20.5%, p = 0.626), and net adverse cardiac event (NACE) (22.1% vs. 21.3%, p = 0.731) between the groups. The ticagrelor or prasugrel group had a lower incidence of recurrent percutaneous coronary intervention (PCI) (12.2% vs. 7.6%, p = 0.006) than the clopidogrel group. However, no differences were observed in the cumulative incidences of 3-year NACE between the ticagrelor or prasugrel and clopidogrel groups., Conclusions: Cumulative incidences of long-term NACE did not differ between the two groups. Therefore, the type and duration of DAPT should be customized for each patient with AMI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Potent P2Y 12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS., Methods: The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting)., Results: A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56-2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups., Conclusions: Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI., Trial Registration: KCT0002356, registered June 13, 2017., (© 2023. The Author(s).)

Although dual antiplatelet therapy for secondary prevention in acute coronary syndrome (ACS) is highly recommended by current guidelines, P2Y 12 inhibitor non-adherence often occurs and devastates prognosis. To evaluate whether the ischemic risk during the early period of clopidogrel noncompliance was increased among ACS patients, a comprehensive search of PubMed, Embase, and Web of Science was conducted to identify studies reporting early ischemic risk after clopidogrel noncompliance in ACS patients. The primary endpoint was a composite of death or myocardial infarction (MI). Effect sizes were synthesized in patients with or without revascularization. A total of 7 observational studies focusing on clopidogrel noncompliance were included in this meta-analysis, whereas no studies involving ticagrelor or prasugrel were retrieved. A significantly increased risk of death or MI 0 to 90 days after clopidogrel noncompliance was found compared with that during 90 to 180 or 90 to 360 days regardless of revascularization (incidence rate ratio [IRR]: 2.01, 95% confidence interval (CI): 1.62-2.49, P  < .001, I 2  = 9%) or not (IRR: 1.61, 95% CI: 1.05-2.48, P  < .001, I 2  = 74%). Patients undergoing percutaneous coronary intervention had a higher risk of death or MI 0 to 90 days after clopidogrel noncompliance compared with 90-180 or 90-360 days irrespective of drug-eluting stent or bare metal stent implantation ( P  < .05 for both). The early ischemic risk after clopidogrel noncompliance is significantly higher than the late risk in ACS patients. Antiplatelet noncompliance remains a serious concern.

Patient response to P2Y12 inhibitor therapy is heterogeneous, and those with high on-treatment platelet reactivity (HTPR) are at an increased risk of thrombotic complications. The aim of our study was to determine whether selecting a high-risk patient group of individuals after complex percutaneous coronary intervention (PCI) would show the clinical benefit of HTPR testing for preventing thrombotic complications. Blood samples of patients after complex PCI were acquired 1 day and 1 month after the intervention. The samples were tested using vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) and platelet function assay (PFA). The occurrence of clinically significant stent thrombosis with repeated revascularization of the target vessel was observed over a 1-year period. One day after PCI, 37% of patients had HTPR as established by VASP-P. One month after PCI, the percentage of patients with HTPR decreased to 30.9%. According to PFA, 1 day after PCI, 33.3% of patients had HTPR. This percentage declined to 19.8% after 1 month. All measurements identified a significantly higher proportion of HTPR in patients on clopidogrel compared to ticagrelor and prasugrel. Two cases of early stent thrombosis and 1 case of late stent thrombosis were identified. Further study of adenosine diphosphate receptor blocker on-treatment response in patients undergoing complex PCI is necessary.

Background: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y 12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y 12 -inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking., Methods: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction., Results: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P  < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P  < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs., Conclusions: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Prof dr. J. M. ten Berg received research grants from AstraZeneca and ZonMw and personal fees from AstraZeneca, Accu-Metrics, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Ferrer, Idorsia, Pfizer and The Medicines Company. All other authors have nothing to declare.

Dual antiplatelet therapy (DAPT) has remained the cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5' diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline for ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.

Aim: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear., Methods: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR., Results: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles., Conclusions: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Objectives: To prevent thrombotic events after angioplasty, current guidelines recommend dual antiplatelet therapy with aspirin and thienopyridine. Clopidogrel is the only thienopyridine currently available in the Brazilian National Health System. The purpose of this study was to determine the cost-effectiveness of prasugrel, an alternative thienopyridine, compared with clopidogrel in patients with acute coronary syndrome and diabetes mellitus who underwent angioplasty., Methods: A state-transition Markov model was created to simulate the progression of diabetic patients after angioplasty. The model had a lifetime horizon and discounted outcomes at a 5% annual rate. The risks of myocardial infarction and death were calculated using data from the diabetes subgroup, and the risks of bleeding were calculated using data from the overall group from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38 trial. Direct costs were estimated using official Brazilian open data. Quality of life values were obtained through literature search. Univariate and multivariate sensitivity analyses were performed., Results: Prasugrel was associated with more quality-adjusted life-years (QALYs) (5.03 vs 4.94) and higher costs (US$975.11 vs US$575.97), resulting in an incremental cost-utility ratio (ICUR) of US$4303.86/QALY. In one-way sensitivity analysis, the costs of prasugrel had the greatest impact on ICUR, followed by the initial age entering the cohort. In the probabilistic sensitivity analysis, all ICUR values simulations were less than one Brazilian gross domestic product per capita/QALY (US $5802.86)., Conclusions: Given the appealing economic profile, the clinical debate between reducing the risk of myocardial infarction and increasing the risk of bleeding may overcome economic concerns in the Brazilian National Health System., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: In this study, we aimed to determine whether potent agents affect in-hospital bleeding and mortality compared to clopidogrel in patients with the acute coronary syndrome in whom tirofiban and P2Y12 inhibitor are used together., Methods: Patients who were treated interventionally between 2015 and 2020 and were using tirofiban were retrospectively screened. Clinical, laboratory, and angiographic findings were obtained from the hospital database. Patients were analyzed by dividing them into clopidogrel and prasugrel/ticagrelor groups., Results: Acute coronary syndrome patients (n = 227) who were treated interventionally were included in this retrospective study. Clopidogrel was given to 93 (41%), ticagrelor to 112 (49.3%), and prasugrel to 22 of the patients (9.7%). Compared to the ticagrelor/prasugrel group, the clopidogrel group was older and more were women, and the history of hypertension and previous coronary artery disease was higher (P, respectively: <.001; .001; .008; .0045). The creatinine value was higher, the basal hemoglobin was lower, and the GRACE (Global Registry of Acute Coronary Events) and CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) scores were higher (P, respectively: .026; .002; .002; <.001). The in-hospital bleeding rate was signifi- cantly higher in the clopidogrel group (P < .001). Although the in-hospital mortality rate was higher, it was not statistically significant (P = .07). Regression analysis showed that GRACE score and gender were associated with in-hospital mortality (P < .001; P=.031, respectively), and only age was associated with in-hospital bleeding (P < .001). No relationship was found with P2Y12 inhibitor., Conclusion: In our study, we found that the combined use of potent P2Y12 inhibitor with tiro- fiban in acute coronary syndrome patients treated interventionally was not different from the use of clopidogrel in terms of in-hospital bleeding and mortality.

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y 12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y 12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y 12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P <0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y 12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y 12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.

Objective: To evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y 12 inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS)., Patients and Methods: MEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y 12 inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y 12 inhibitors and clopidogrel in patients with AMI-CA/CS., Results: Eight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y 12 cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies)., Conclusion: In patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y 12 inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS., Methods and Results: We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments., Conclusion: In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS., Study Registration Number: This study is registered in PROSPERO (CRD42021258603)., Key Question: A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored., Key Finding: In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality., Take Home Message: A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Novel P2Y12 inhibitors prasugrel and ticagrelor were approved for patients with acute coronary syndrome (ACS) in 2009 and 2011, respectively. We assessed the association of racial, ethnic, and socioeconomic factors with initiation of and adherence to novel P2Y12 inhibitors in a commercially insured population., Methods: We performed a retrospective cohort analysis of adults undergoing percutaneous coronary intervention with placement of a drug-eluting stent, stratified by ACS status, between January 2008 and December 2016 using Clinformatics Data Mart (OptumInsight). We estimated multivariable logistic regression models to identify factors associated with the initiation of clopidogrel vs novel P2Y12 inhibitors as well as subsequent 6-month medication adherence, assessed via pharmacy records., Results: A total of 55,664 patients were included in the analysis. Hispanic ethnicity was independently associated with the initiation of clopidogrel compared with novel P2Y12 inhibitors among ACS patients (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P<.01). ACS patients with an annual median household income of over $100,000 were less likely to be started on clopidogrel when compared with those who earned less than $40,000 (OR, 0.67; 95% CI, 0.61-0.75; P<.01). Black race, Hispanic ethnicity, and lower household income were each associated with significantly reduced odds of P2Y12 inhibitor adherence., Conclusion: Hispanic ethnicity and lower household income were associated with novel P2Y12 inhibitor initiation, and non-White race and ethnicity were associated with lower P2Y12 inhibitor adherence over 6-month follow-up. These findings highlight continued inequity of care, even in an insured population, and point to a need for new strategies to close these gaps.

Competing Interests: Competing interests: Alan Bell reports consulting fees from AstraZeneca, Bayer and Sanofi; speaker fees from AstraZeneca; and board membership with Thrombosis Canada, Hypertension Canada and the Canadian Cardiovascular Society. Sol Stern reports honoraria from Bayer, Pfizer, Bristol Myers Squibb and Sea Courses Inc. Shaun Goodman reports research grant support from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Eli Lilly, Esperion, Ferring Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi, Heart and Stroke Foundation of Ontario, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Center for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Center, PERFUSE Research Institute and TIMI Study Group (Brigham Health). He also reports consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, PendoPharm of Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Valeo Pharma, Canadian Heart Research Centre and MD Primer, and speaking fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Novartis, PendoPharm of Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Valeo Pharm, Canadian Heart Research Centre and MD Primer. He sits on boards with American Regent of Daiichi-Sankyo and Novo Nordisk and is co-director of the Canadian VIGOUR Centre. All competing interests are outside the submitted work. No other competing interests were declared.

The rapid introduction of dual antiplatelet therapy (DAPT) is important for patients with acute myocardial infarction (AMI). The risks and benefits of reduced-dose prasugrel (20 mg loading and 3.75 mg maintenance) over clopidogrel have not been fully discussed. The purpose of this study was to compare the 90-days clinical outcomes of AMI between prasugrel-based DAPT and clopidogrel-based DAPT. We included 534 AMI patients and divided them into the clopidogrel group (n = 330) and the prasugrel group (n = 204). The primary endpoint was the total ischemic events and total bleeding events. In all, 52 ischemic events and 35 bleeding events were observed during the study period. The total ischemic events were similar between the clopidogrel and the prasugrel groups (P = 0.385). The total bleeding events were similar between the clopidogrel and the prasugrel groups (P = 0.125). The multivariate Cox hazard analysis showed that prasugrel was not associated with the total ischemic events (hazard ratio (HR) 0.955, 95% confidence interval (CI) 0.499-1.829, P = 0.890) and was not associated with the total bleeding events after controlling confounding factors (HR 0.972, 95% CI 0.528-1.790, P = 0.927). In conclusion, as compared to clopidogrel, the reduced dose of prasugrel was not associated with the excess risk of bleeding or the excess risk of ischemic events. Our real-world data support the current regimen of prasugrel for AMI patients who underwent primary percutaneous coronary intervention.

Background: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD)., Methods and results: We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y 12 reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009)., Conclusions: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Background and Objectives: Prasugrel and ticagrelor have superior efficacy compared with clopidogrel in moderate CKD but have not been studied in kidney failure. The study objective is to determine the effectiveness and safety of prasugrel and ticagrelor in kidney failure., Design, Setting, Participants, & Measurements: This retrospective cohort study used United States Renal Data System data from 2012 to 2015. We identified all patients on dialysis who received a drug-eluting stent and were alive at 90 days after stent implantation. Inverse probability-weighted Cox proportional hazard models were used. Weights were estimated with propensity scores for multiple treatments., Results: This cohort included 6648 patients on clopidogrel, 621 on prasugrel, and 449 on ticagrelor. A total of 3279 primary composite (cardiovascular death, myocardial infarction, or stroke) and 2120 clinically relevant bleeding events were observed. The incidence of the primary composite outcome of cardiovascular death, myocardial infarction, or stroke at 12 months was similar across the three treatment groups. The absolute event rate in the unweighted cohort was 144 events per 100 patient-years for clopidogrel, 126 for prasugrel, and 161 for ticagrelor. For prasugrel versus clopidogrel, the weighted hazard ratio was 0.96 (95% confidence interval, 0.82 to 1.11; P =0.58). For ticagrelor versus clopidogrel, the hazard ratio was 1.00 (95% confidence interval, 0.83 to 1.20; P =0.98). A numerically higher incidence of clinically relevant bleeding was seen with prasugrel or ticagrelor compared with clopidogrel (weighted hazard ratio, 1.15; 95% confidence interval, 0.95 to 1.38 and weighted hazard ratio, 1.13; 95% confidence interval, 0.91 to 1.40, respectively)., Conclusions: Prasugrel or ticagrelor does not seem to be associated with significant benefits compared with clopidogrel in patients with kidney failure treated with drug-eluting stents., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021&#95;04&#95;02&#95;CJN12120720.mp3., (Copyright © 2021 by the American Society of Nephrology.)

Objective: To study the use of CYP2C19 genotyping to guide P2Y 12 inhibitor selection to maximize efficacy, and attenuate risk in appropriate patients who underwent PCI for CAD., Methods: We performed a retrospective analysis of 868 patients with CAD who received CYP2C19 genotyping after PCI and changed P2Y 12 inhibitor based on the results. Patients were divided into two groups based on clopidogrel metabolizer status. Group I: Intermediate (IM) and poor metabolizers (PM). Group II: Ultra-rapid (UM), rapid (RM) and normal metabolizers (NM). Each group was then categorized to one of two treatment arms guided by CYP2C19 genotype. Category 1: IM/PM started on clopidogrel, switched to ticagrelor or prasugrel; 2:IM/PM started on ticagrelor/prasugrel, continued these medications; 3: UM/RM/NM started on ticagrelor/prasugrel, switched to clopidogrel; 4: UM/RM/NM started on clopidogrel, continued clopidogrel. Death due to cardiac causes, bleeding events, non-fatal MI, target vessel revascularization (TVR), and MACE in all four categories were considered at 1, 6 and 12 months., Results: We did not observe significant difference between phenotypes for MACE at 1 (p = 0.274), 6 (p = 0.387), and 12 months (p = 0.083). Death due to cardiac causes, MI, and bleeding events were not significant at 1, 6, and 12 months. There was no significant difference in TVR at 6 (p = 0.491), and 12 months (p = 0.423) except at 1 month (p = 0.012)., Conclusion: CYP2C19 genotype-based intervention can be implemented effectively and reliably to guide selection of P2Y 12 inhibitor to optimize patient quality and safety when appropriate in post PCI patients., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied., Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP., Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094-1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010-1.466]), hemorrhagic stroke (13 events, 3.247 [1.660-6.296]), ischemic events (142 events, 1.219 [1.020-1.466]), and bleeding events (47 events, 1.629 [1.172-2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220-4.225] per 10-mm Hg increase; 3.051 [2.179-4.262]; 3.276 [1.172-9.092]; 2.865 [2.042-4.011]; 2.764 [1.524-5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP., Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp; Unique identifier: JapicCTI-111582.

Background: The risks of bleeding and cardiovascular events in high bleeding risk (HBR) Japanese patients undergoing percutaneous coronary intervention (PCI) while receiving single-antiplatelet therapy (SAPT) remains unknown. We aimed to evaluate the frequency of bleeding and cardiovascular events associated with prasugrel monotherapy after short-term dual-antiplatelet therapy (DAPT) in Japanese HBR patients after PCI., Methods and results: The PENDULUM mono study was a multicenter, non-interventional, prospective registry (n=1,173). The primary endpoint was the cumulative incidence of clinically relevant bleeding (CRB; Bleeding Academic Research Consortium types 2, 3, and 5) from 1 to 12 months after PCI. Secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE). The proportion of patients who received prasugrel monotherapy at 12 months after PCI was 79.7%, and no cases of stent thrombosis were observed among these patients. The cumulative incidence of CRB was 3.2% from 1 to 12 months after PCI; that of MACCE was 3.8%. Severe anemia, chronic kidney disease, oral anticoagulant use at discharge, and heart failure were significantly associated with CRB., Conclusions: Among HBR patients undergoing PCI who were not suitable for concomitant aspirin and were scheduled for prasugrel monotherapy, most patients were on prasugrel monotherapy after DAPT. Cumulative incidences of CRB and MACCE after periprocedural period were 3.2% and 3.8%, respectively, and no cases of stent thrombosis were reported. SAPT might be a suitable alternative to DAPT.

Background Peripheral artery disease (PAD) is a known risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. However, in some studies PAD is not an independent risk factor. We sought to examine the independent impact of PAD on a large prospective percutaneous coronary intervention registry. Methods and Results From our single-center prospective percutaneous coronary intervention registry, we have retrospectively analyzed 25 690 patients (years 2004-2018). We examined the influence of PAD on short- and long-term outcomes using both regression and propensity-matched analyses. Patients with documented PAD (n=1610, 6.3% of total) were older (66.7±10.8 versus 65.4±12.1, P <0.01), had higher rates of diabetes mellitus (69.3% versus 46.3%, P <0.01), hypertension (92.1% versus 76.1%, P <0.01) and renal failure (38.3% versus 18.2%, P <0.01). There were no differences in the rates of stable versus acute presentations, but less were treated with Prasugrel and Ticagrelor (3.3% versus 8.0% and 7.9% versus 11.9%, respectively, P <0.001 for both). Both 30-day and 3-year rates of all-cause death and major adverse cardiac events were higher for patients with PAD versus control (4.9% versus 2.1% and 7.3% versus 3.3% death and major adverse cardiac events at 30 days, respectively; 43.4% versus 29.0% and 55.0% versus 37.8%, respectively at 3 years, P <0.001 for all). Following multivariate analysis, the presence of PAD was associated with a higher risk of both death (hazard ratio [HR], 1.66; CI 1.52-1.83; P <0.001) and major adverse cardiac events (HR, 1.51; CI, 1.40-1.64; P <0.001). Conclusions PAD constitutes an independent risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. Further studies are needed to ascertain which effective therapies may mitigate this risk.

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention., Methods: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization., Results: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P =0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P =0.83), stroke (1.3% versus 1.0%; P =0.46), and definite stent thrombosis (1.8% versus 1.0%; P =0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P =0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P =0.36)., Conclusions: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Objectives: The objective of this study is to examine the temporal trend of antiplatelet prescribing pattern during index hospitalisation discharge in Hong Kong (HK) acute coronary syndrome (ACS) population., Design: The study is a retrospective observational cohort study., Setting: The study retrieved data from electronic health record from Hospital Authority (HA), HK., Participants: The study included patients aged 18 years old or above, who were admitted to seven institutions under HA with diagnosis of ACS during 2008-2017., Primary and Secondary Outcome Measures: The primary outcome was the frequency of antiplatelet therapy prescription at the point of index hospitalisation discharge each year during 2008-2017. Association between demographics, baseline comorbidities, procedures and antiplatelet prescription were examined as secondary outcome using multivariate logistic regression model, with commonly used antiplatelet groups selected for comparison., Results: Among the included 14 716 patients, 5888 (40.0%) discharged with aspirin alone, 6888 (46.8%) discharged with dual antiplatelet therapy (DAPT) with clopidogrel, and 973 (6.6%) discharged with DAPT with prasugrel/ticagrelor. Prescribing rate of aspirin alone decreased substantially from 56.8% in 2008 to 27.5% in 2017. Utilisation of DAPT with clopidogrel increased from 33.7% in 2008 to 52.7% in 2017. Use of DAPT with prasugrel/ticagrelor increased from 0.3% in 2010 to 15.3% in 2017. Compared with those prescribed with DAPT with clopidogrel, male patients (adjusted OR (aOR) 1.34, 95% CI 1.09 to 1.65), patients with non-ST-elevation myocardial infarction (aOR 2.50, 1.98 to 3.16) or ST-elevation myocardial infarction (aOR 3.26, 2.59 to 4.09), use of glycoprotein IIb/IIIa (aOR 3.03, 2.48 to 3.68) or undergoing percutaneous coronary intervention (aOR 3.85, 3.24 to 4.58) or coronary artery bypass graft (aOR 6.52, 4.63 to 9.18) during index hospitalisation, concurrent use of histamine-2 receptor antagonists (aOR 1.35, 1.10 to 1.65) or proton pump inhibitors (aOR 3.57, 2.93 to 4.36) during index hospitalisation discharge were more likely to be prescribed with DAPT with prasugrel/ticagrelor. Patients with older age (aOR 0.97, 0.96 to 0.97), diabetes (aOR 0.68, 0.52 to 0.88), chronic kidney disease (aOR 0.43, 0.22 to 0.85) or concurrent use of oral anticoagulant (aOR 0.16, 0.07 to 0.42) were more likely to received DAPT with clopidogrel., Conclusions: Use of DAPT with prasugrel/ticagrelor was suboptimal yet improving during 2008-2017 in HK patients with ACS. Considering DAPT, predictors for clopidogrel prescription, compared with prasugrel/ticagrelor, were consistent with identified risk factors of bleeding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI)., Objectives: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management., Methods: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5., Results: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month., Conclusions: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800)., Competing Interests: Author Relationship With Industry Dr. Neumann has received lecture fees, paid to his institution, from Amgen, Daiichi-Sankyo, Novartis, and Ferrer; has received lecture fees, paid to his institution, and consulting fees, paid to his institution, from AstraZeneca and Boehringer Ingelheim; has received grant support and lecture fees, paid to his institution, from Pfizer, Biotronic, Edwards Lifesciences, Bayer HealthCare, and GlaxoSmithKline; and has received grant support from Medtronic, Abbott Vascular, and Boston Scientific. Dr. Sibbing has received personal fees from Bayer AG, Sanofi, AstraZeneca, Pfizer, Ferrer, and Daiichi-Sankyo; and has received grants and personal fees from Roche Diagnostics. Dr. Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St. Jude Medical; 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, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr. Liebetrau has received consulting fees or honoraria from AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer, and Thermo Fisher; and has received research grants from Deutsche Herzstiftung, Kerckhoff-Stiftung, and Kühl-Stiftung outside the submitted work. Dr. Liebetrau’s institution has received payments for participation in clinical study programs from Abbott, AstraZeneca, Bayer, Biosensors, Boston Scientific, Daiichi-Sankyo, and Neovasc. Dr. Hamm has received Advisory Board and speaker fees from AstraZeneca and Daiichi-Sankyo. Dr. Sager has received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (STRATO), the Else-Kröner-Fresenius-Stiftung, the Deutsche Herzstiftung, and the Deutsche Forschungsgemeinschaft. Dr. Joner has received personal fees from Biotronik, Orbus Neich, Boston Scientific, Edwards, AstraZeneca, and Recor; and has received grants from Boston Scientific, Edwards, and Amgen. Dr. Trenk has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Ferrer, Pfizer, and Sanofi; and has received research grants from Deutsche Herzstiftung and PharmCompNet Baden-Wuerttemberg: Kompetenznetzwerk Pharmakologie Baden-Wuerttemberg outside the submitted work. Dr. Trenk’s institution has received payments for participation in clinical study programs from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Doasense, Esperion, Idorsia, and Otsuka. Dr. Schunkert has received personal fees from Merck Sharp & Dohme, Amgen, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Servier, Brahms, Bristol Myers Squibb, Medtronic, Sanofi, Synlab, Pfizer, and Vifor; and has received grants and personal fees from AstraZeneca. Dr. Schüpke has received grants from the DZHK (German Center for Cardiovascular Research) and the Else Kröner-Fresenius-Stiftung; has received consulting fees from Bayer Vital GmbH; and has received lecture fees from Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Dual antiplatelet therapy is the mainstay therapy in patients with acute coronary syndrome. The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. The newer P2Y12 inhibitors (prasugrel and ticagrelor) have better efficacy than clopidogrel. Prasugrel provides greater inhibition of platelet aggregation and has a rapid onset of action. Current acute coronary syndrome guidelines recommend the use of both newer P2Y12 inhibitors. However, emerging data have shown that prasugrel is more efficient than ticagrelor in reducing the incidence of nonfatal myocardial infarction, stroke or cardiovascular death, without increased risk of major bleeding.