Impact of Society Guidelines on Trends in Use of Newer P2Y12 Inhibitors for Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 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 P2Y12 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 P2Y12 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, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 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.

An Aspirin-Free Strategy for Immediate Treatment Following Complex Percutaneous Coronary Intervention.

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).

[Antithrombotic therapy in acute coronary syndrome]. / Antithrombotische Therapie beim akuten Koronarsyndrom.

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.

Prehospital crushed versus integral prasugrel loading dose in STEMI patients with a large myocardial area.

BACKGROUND: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI). AIMS: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose. METHODS: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area. RESULTS: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; pinteraction=0.009). CONCLUSIONS: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.

Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory.

Genotype based personalized antiplatelet therapy in the setting of percutaneous coronary intervention (PCI) has been studied in clinical trials. Despite the demonstrated risk associated with CYP2C19 loss-of-function (LoF) carriage in clopidogrel-treated PCI patients, real-world implementation of genotyping for PCI has been low. The goal of the current study was to provide CYP2C19 genotype information to the interventionalist prior to the completion of the catheterization to facilitate immediate personalized antiplatelet therapy. Routine personalization of P2Y12 inhibitor therapy for PCI in a community hospital cardiac catheterization laboratory by POC genotyping with the SpartanRx system was first offered in February 2017. A best practice advisory (BPA) based on the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy was placed in the electronic health record prescription medication ordering system. By December 2019, 1,052 patients had CYP2C19 genotype testing, 429 patients underwent PCI with genotype guided antiplatelet therapy, and 250 patients underwent PCI without genotype testing and received antiplatelet therapy at the discretion of the treating physician. BPA compliance was 93. 87% of LoF allele carriers were prescribed ticagrelor or prasugrel whereas 96% of non-LoF allele carriers were prescribed clopidogrel. The genotyping results were available within 1 h and made immediately available for decision making by the interventional cardiologist. POC CYP2C19 genotyping is feasible in a community hospital catheterization laboratory and is associated with high rate of best practice compliance.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622.

Prasugrel Single Antiplatelet Therapy versus Aspirin and Clopidogrel Dual Antiplatelet Therapy for Flow Diverter Treatment for Cerebral Aneurysms: A Retrospective Multicenter Study.

BACKGROUND AND PURPOSE: The optimal antiplatelet regimen after flow diverter treatment of cerebral aneurysms is still a matter of debate. A single antiplatelet therapy might be advantageous in determined clinical scenarios. This study evaluated the efficacy and safety of prasugrel single antiplatelet therapy versus aspirin and clopidogrel dual antiplatelet therapy. MATERIALS AND METHODS: We performed a post hoc analysis of 4 retrospective multicenter studies including ruptured and unruptured aneurysms treated with flow diversion using either prasugrel single antiplatelet therapy or dual antiplatelet therapy. Primary end points were the occurrence of any kind of procedure- or device-related thromboembolic complications and complete aneurysm occlusion at the latest radiologic follow-up (mean, 18 months). Dichotomized comparisons of outcomes were performed between single antiplatelet therapy and dual antiplatelet therapy. Additionally, the influence of various patient- and aneurysm-related variables on the occurrence of thromboembolic complications was investigated using multivariable backward logistic regression. RESULTS: A total of 222 patients with 251 aneurysms were included, 90 (40.5%) in the single antiplatelet therapy and 132 (59.5%) in the dual antiplatelet therapy group. The primary outcome-procedure- or device-related thromboembolic complications-occurred in 6 patients (6.6%) of the single antiplatelet therapy and in 12 patients (9.0%) of the dual antiplatelet therapy group (P = .62; OR, 0.712; 95% CI, 0.260-1.930). The primary treatment efficacy end point was reached in 82 patients (80.4%) of the single antiplatelet therapy and in 115 patients (78.2%) of the dual antiplatelet therapy group (P = .752; OR, 1.141; 95% CI, 0.599-2.101). Logistic regression showed that non-surface-modified flow diverters (P = .014) and fusiform aneurysm morphology (P = .004) significantly increased the probability of thromboembolic complications. CONCLUSIONS: Prasugrel single antiplatelet therapy after flow diverter treatment may be as safe and effective as dual antiplatelet therapy and could, therefore, be a valid alternative in selected patients. Further prospective comparative studies are required to validate our findings.

Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

Comparison of ticagrelor and clopidogrel in anemic patients with acute coronary syndrome: efficacy and safety outcomes over one year.

OBJECTIVE: This retrospective study aimed to investigate the potential impact of ticagrelor and clopidogrel treatment on cardiovascular outcomes in patients with anemia and acute coronary syndrome (ACS) and to provide insights into the optimal therapeutic approach for this vulnerable patient population. METHODS: A retrospective research design was employed, involving patients diagnosed with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) between 2014 and 2021. Inclusion criteria required a hemoglobin level below 12 mg/dL and a minimum 12-month P2Y12 inhibitor treatment. Comprehensive clinical, biochemical, and echocardiographic data were collected from the hospital's electronic repository. The primary efficacy endpoint was major adverse cardiovascular events (MACE), encompassing total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke. Major hemorrhage was the primary safety endpoint. Secondary outcomes included total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke, individually. RESULTS: Patients treated with ticagrelor (n = 118) and clopidogrel (n = 538) were compared. No significant difference was observed in major adverse cardiovascular events (MACE) and major bleeding between ticagrelor and clopidogrel treatment groups (MACE: clopidogrel 10.0% vs. ticagrelor 11.0%, p = 0.75; major bleeding: clopidogrel 2.8%, ticagrelor 2.5%, p = 0.88). Patients with hemoglobin levels ≤ 8 mg/dL demonstrated significantly higher MACE and major bleeding rates in the ticagrelor group (p = 0.008 and p = 0.002, respectively). Among patients aged ≥ 75 years, ticagrelor treatment was associated with a higher risk of major bleeding (p = 0.04). CONCLUSIONS: Ticagrelor and clopidogrel exhibited comparable efficacy and safety outcomes in anemic ACS patients over a one-year period. Although ticagrelor demonstrated superiority in reducing ischemic events, it is crucial to recognize the limitations of retrospective studies in informing clinical practice. This study offers valuable insights into tailoring antiplatelet therapy for anemic ACS patients and provides guidance for personalized treatment strategies, acknowledging the hypothesis-generating nature of retrospective analyses.

Genetic-Guided Pharmacotherapy for Coronary Artery Disease: A Systematic and Critical Review of Economic Evaluations.

BACKGROUND: Genetic-guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost-effectiveness. METHODS AND RESULTS: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model-based cost-utility analyses alone, or alongside cost-effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin-converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non-PGx), PGx was more effective and more costly than non-PGx clopidogrel (28/43) but less costly than non-PGx prasugrel (10/15) and less costly and less effective than non-PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. CONCLUSIONS: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost-effective, but findings varied based on the non-PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.

Comparison of Ticagrelor and Clopidogrel in Patients With Acute Coronary Syndrome at High Bleeding or Ischemic Risk.

Current guidelines recommend individualizing the choice and duration of P2Y12 inhibitor therapy based on the trade-off between bleeding and ischemic risk. However, whether a potent P2Y12 inhibitor (ticagrelor) or a less potent one (clopidogrel) is more appropriate in patients with acute coronary syndrome (ACS) in the setting of high bleeding or ischemic risk is not clear. The study aimed to compare the clinical outcomes of clopidogrel and ticagrelor in patients with ACS at high bleeding or ischemic risk. A total of 5,713 patients with ACS were included in this retrospective study. The Cox proportional hazard regression model was adjusted by applying the inverse probability weighted approach to reduce treatment selection bias. The primary clinical outcome was all-cause death. Secondary outcomes included in-hospital death, ACS, target vessel revascularization, stent thrombosis, stroke, or clinically significant or major bleeding. The median follow-up duration was 53.6 months. After multivariable Cox model using an inverse probability weighted approach, all-cause death in the overall population and subgroups of patients at high bleeding risk, and/or at high ischemic risk were not significantly different between clopidogrel and ticagrelor. Rates for secondary outcomes were also similar between the groups. In conclusion, ticagrelor and clopidogrel are associated with comparable clinical outcomes in patients with ACS irrespective of bleeding and ischemic risk.

An overview of the utility of prasugrel hydrochloride as a treatment option for ischemic stroke.

INTRODUCTION: Prasugrel, a potent P2Y12 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 P2Y12 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.

The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the FORCE-ACS Registry.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-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.

Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Limited data comparing prasugrel and ticagrelor in acute coronary syndrome are available. Online databases, including MEDLINE and Cochrane Central, were queried to compare these drugs. The primary outcomes of this meta-analysis are myocardial infarction (MI), all-cause mortality, cardiovascular mortality, noncardiovascular mortality, stent thrombosis, and stroke. The secondary outcome is major bleeding. A total of 9 studies, including 94,590 patients (prasugrel group = 32,759; ticagrelor group = 61,831), were included in this meta-analysis. The overall mean age was 62.73 years, whereas the mean age for the ticagrelor and prasugrel groups was 63.80 and 61.65 years, respectively. Prasugrel is equally effective as compared with ticagrelor in preventing MI. There was no difference between the 2 groups regarding all-cause mortality, stent thrombosis, stroke, or major bleeding. In patients with acute coronary syndrome, prasugrel is equally effective when compared with ticagrelor in preventing MI.

High On-Treatment Platelet Reactivity in Patients Undergoing Complex Percutaneous Coronary Interventions.

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.

The Increased Ischemic Risk During the Early Period After Clopidogrel Noncompliance in Patients with Acute Coronary Syndrome: A Meta-Analysis.

Although dual antiplatelet therapy for secondary prevention in acute coronary syndrome (ACS) is highly recommended by current guidelines, P2Y12 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, I2 = 9%) or not (IRR: 1.61, 95% CI: 1.05-2.48, P < .001, I2 = 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.

Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.

BACKGROUND: Intracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous coronary intervention (PCI) on histological characteristics of thrombus formation. OBJECTIVE: In this study, we investigate the impact of preinterventional administration of the P2Y12-inhibitors clopidogrel and prasugrel on thrombus composition, highlighting significant changes associated with the antiplatelet pre-treatment. METHODS: We prospectively enrolled 104 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing immediate PCI and thrombus aspiration by immunohistochemical staining along with RNA-sequencing employing Nanostring analysis. Fifty-two patients were treated with either prasugrel loading (60 mg) or clopidogrel loading (600 mg) prior to PCI, respectively. RESULTS: In Patients with STEMI, intracoronary thrombus architecture was significantly altered between patients pre-treated with prasugrel when compared to clopidogrel. Fibrin content of thrombi was significantly decreased (41.8 % versus 66.7 %, p = 0.009) after pre-treatment with prasugrel compared to clopidogrel. Furthermore, levels of MPO positive cells in intracoronary thrombi were significantly decreased in patients with prasugrel pre-treatment (90.5 versus 201.1, p = 0.014) indicating an association of antiplatelet pre-treatment and the inflammatory responses during thrombus formation. Most strikingly, we observed significant differences among both pre-treatment groups regarding altered RNA expression and signaling pathways of thrombo-inflammatory processes within the thrombotic material, which were independently associated with antiplatelet strategies. CONCLUSIONS: Our study elucidates the impact of antiplatelet pre-treatment on thrombus remodeling and architecture, thereby lowering the risk of recurrent adverse cardiovascular events in prasugrel-treated patients.

Usefulness of the PRECISE-DAPT score at differentiating between ticagrelor and prasugrel for dual antiplatelet therapy initiation.

As a part of dual antiplatelet therapy (DAPT), prasugrel or ticagrelor is prescribed along with aspirin to patients of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to assess if the PRECISE-DAPT score, which provides prediction of bleeding during DAPT, could be used to choose between prasugrel and ticagrelor for DAPT initiation. 181 patients out of which 71 received prasugrel and 110 received ticagrelor were enrolled in this prospective cohort study. PRECISE-DAPT score was calculated for everyone and was used to dichotomize patients into two subgroups (score <25 and ≥25). After balancing potential confounders in baseline characteristics of the subgroups using propensity scores, comparison of a composite outcome of 4-point major adverse cardiovascular events (4P-MACE) (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization due to stent thrombosis) and bleeding (any type as defined by the Bleeding Academic Research Consortium) within 1-year post-PCI was performed among the subgroups using Cox proportional hazards regression. Prasugrel was associated with lower and comparatively higher 4P-MACE events in subgroups with score ≥25 (HR: 0.17; 95% CI, 0.04-0.77) and score <25 (HR: 3.58; 95% CI, 0.62-20.70) respectively. For bleeding outcome, prasugrel trended towards more clinical benefit for scores ≥25 (HR: 0.44; 95% CI, 0.10-1.93) than <25 (HR: 0.93; 95% CI, 0.13-6.58). Therefore, prasugrel was associated with better clinical effectiveness and trended towards a lower bleeding risk compared to ticagrelor within 1-year post-PCI for those with a high PRECISE-DAPT score (≥25). This finding requires validation through larger studies.