Current Antithrombotic Treatments for Cardiovascular Diseases: A Comprehensive Review.

Antithrombotic therapies (ATT) play a pivotal role in the management of cardiovascular diseases, aiming to prevent ischemic events while maintaining a delicate balance with the patient's bleeding risk. Typically, ATT can be classified into antiplatelet and anticoagulant therapies. Their application spans a broad spectrum of cardiovascular conditions, ranging from ischemic heart disease to atrial fibrillation, encompassing venous thromboembolisms and innovative structural interventional cardiology procedures. The global burden of cardiovascular diseases is steadily increasing, often giving rise to overlapping clinical presentations. Accordingly, the adoption of combined pharmacological approaches becomes imperative, potentially disrupting the delicate equilibrium between ischemic and bleeding risk, thus leading to nuanced pharmacotherapeutic pathways. In this context, contemporary investigations strive to identify a convergence point that optimizes the duration of medical therapy while addressing the need for antithrombotic effects, especially in the context of ischemic heart disease. This review aims to comprehensively revisit the main antithrombotic strategies in cardiovascular diseases, with the intention of enhancing a systematic approach which is key for the effective clinical management of these patients. Also, the review will examine the most impactful studies that have established the groundwork for current scientific evidence, with acknowledgement of special populations. Finally, we will cast a gaze into the future of this dynamic and evolving research field, exploring forthcoming perspectives and advancements.

Update on antithrombotic therapy and body mass. A Clinical consensus Statement of the ESC Working Group on Cardiovascular Pharmacotherapy and the ESC Working Group on Thrombosis.

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimising antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

The recent study by Kaiwen Wang et al., titled "Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage," explores the association between postoperative intracranial bleeding (PIB) and various risk factors, including smoking, pre-hemorrhagic antiplatelet therapy, and dyslipidemia. While the study highlights that smoker, particularly women, are at increased risk for subarachnoid hemorrhage and acknowledges the risks of pre-hemorrhagic antiplatelet use, it overlooks the potential risk of PIB associated with early postoperative aspirin administration. This critique underscores the need to approach the study's findings with caution, given the broader context of aspirin's risk profile. Specifically, aspirin has been associated with a 37% higher relative risk of any intracranial hemorrhage, as indicated by other randomized trials. Additionally, the study's implications regarding the benefits of aspirin in stroke prevention must be critically evaluated, as the increased risk of intracranial bleeding may outweigh the potential benefits. This abstract emphasizes the importance of careful consideration of aspirin's adverse effects in the context of postoperative care.

Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy: results from a large tertiary care hospital.

Antiplatelet therapy is crucial for reducing thrombotic events in patients with atherosclerotic disease, but the response vary widely among individuals. The identification of patients at high (HPR), optimal (OPR) or low platelet reactivity (LPR) is dependent on high interlaboratory variability. We report results of a large dataset of patients to assess the gold standard light transmission aggregometry (LTA). A total of 11,913 patients who sequentially underwent LTA assessment using several stimuli (ADP-2µM, collagen-2 µg/ml, arachidonic acid 0.5 mM, epinephrine 10µM) with a standardized methodology between 2004 and 2022 were screened. After application of inclusion-exclusion criteria, 5,901 patients were included and divided into five groups: healthy-volunteers (HV; N = 534); controls (CTR; N = 1073); aspirin-treated patients (ASA; 75-150 mg/die; N = 3280); clopidogrel-treated patients (CLOP; 75 mg/die; N = 495) and patients treated with dual antiplatelet therapy, ASA plus CLOP (DAPT; N = 519). The mean PA% in response to ADP 2 µm was 72.4 ± 33.3 in the CTR population, 40.6 ± 29.9 in the ASA group, 25.1 ± 35.1 in the CLOP group and 10.2 ± 18.5 in the DAPT group. The mean PA% in response to collagen 2 ug/ml was 90.7 ± 10.5 in the CTR population, 40.8 ± 26.3 in the ASA group, 79.4 ± 21.8 in the CLOP group and 17.9 ± 19.9 in the DAPT group. The percentage of patients at OPR following ADP stimuli was 66%, 25%, and 26%, in the ASA, CLOP, and DAPT group, respectively. The percentage of patients at OPR following collagen stimuli was 56%, 22%, and 41%, in the ASA, CLOP, and DAPT group, respectively. LTA was significantly increased in response to ADP (72.4 ± 33.3vs62.7 ± 37.1; p < 0.001) and AA (90.7 ± 15.6vs87.6 ± 20.5; p < 0.001) in CTR compared to HV. Our findings support the concept that a significant proportion of individuals present a hyper- or hypo-reactive platelet phenotype potentially affecting the safety and efficacy of antiplatelet therapy. The variability in response to antiplatelet therapy was particularly evident in patients undergoing single as opposed to dual antiplatelet therapy regimens. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.

Should We Use Aspirin or P2Y12 Inhibitor Monotherapy in Stable Ischemic Heart Disease?

PURPOSE OF REVIEW: To summarize the recent evidence and guideline recommendations on aspirin or P2Y12 inhibitor monotherapy in patients with stable ischemic heart disease and provide insights into future directions on this topic, which involves transition to a personalized assessment of bleeding and thrombotic risks. RECENT FINDINGS: It has been questioned whether the evidence for aspirin as the foundational component of secondary prevention in patients with coronary artery disease aligns with contemporary pharmaco-invasive strategies. The recent HOST-EXAM study randomized patients who had received dual antiplatelet therapy for 6 to 18 months without ischemic or major bleeding events to either clopidogrel or aspirin for a further 24 months, and demonstrated that the patients in the clopidogrel arm had significantly lower rates of both thrombotic and bleeding complications compared to those in the aspirin arm. The patient-level PANTHER meta-analysis showed that in patients with established coronary artery disease, P2Y12 inhibitor monotherapy was associated with lower rates of myocardial infarction, stent thrombosis as well as gastrointestinal bleeding and hemorrhagic stroke compared to aspirin monotherapy, albeit with similar rates of all-cause mortality, cardiovascular mortality and major bleeding. Long-term low-dose aspirin is recommended for secondary prevention in patients with stable ischemic heart disease, with clopidogrel monotherapy being acknowledged as a feasible alternative. Dual antiplatelet therapy for six months after percutaneous coronary intervention remains the standard recommendation for patients with stable ischemic heart disease. However, the duration of dual antiplatelet therapy may be shortened and followed by P2Y12 inhibitor monotherapy or prolonged based on individualized evaluation of the patient's risk profile.

2023 European Society of Cardiology guidelines for the management of acute coronary syndromes : Statement of endorsement by the NVVC.

This review discusses the new recommendations in the 2023 European Society of Cardiology guidelines on the management of acute coronary syndrome and provides a perspective on topics specific to clinical practice in the Netherlands, including pre-treatment, antiplatelet agent strategies, the use of risk scores and logistical considerations with regard to the timing of coronary angiography.

Time to treatment and disability attributed to index stroke in the POINT trial.

BACKGROUND: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, dual antiplatelet therapy (DAPT) was associated with reduced disability attributable to the index stroke compared to antiplatelet monotherapy. However, it is unknown whether earlier treatment with DAPT versus aspirin is associated with greater benefit. METHODS: We analyzed patients enrolled in POINT with minor ischemic stroke who had available data recording the treatment initiation time and modified Rankin Scale (mRS) at 90 days. Patients were randomized to DAPT (aspirin plus clopidogrel) vs. aspirin alone within 12 h of symptom onset. We estimated the effect of DAPT on disability (defined as mRS>1) ascribed to the index event and major hemorrhage at 90 days, stratified by tertiles of time from symptom onset-to-treatment-initiation. RESULTS: A total of 2559 patients were included; median onset-to-treatment-initiation time was 8.3 h (IQR:5.8-11.0). Comparing DAPT to aspirin, the rate of disability attributed to the index event at 90-day follow-up was 5.1 % vs. 8.6 % (OR 0.57; 95 % CI:0.33-0.99) in patients treated <6.7 h, 7.5 % vs. 9.9 % (OR 0.74; 95 % CI:0.45-1.19) in those treated 6.7-10.0 h, and 8.6 % vs. 10.6 % (OR 0.80; 95 % CI:0.50-1.26) in those treated >10.0 h after symptom onset (p for interaction=0.65). There was no difference in major hemorrhage across time strata. CONCLUSIONS: While not statistically significant, these results suggest the possibility of greater efficacy at reducing disability ascribed to minor stroke with earlier treatment with DAPT compared to aspirin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Identifier: NCT00991029.

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Defining short-term outcomes of minor ischemic stroke due to small artery occlusion in the era of dual antiplatelet treatment: A READAPT study sub-analysis.

BACKGROUND: The outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients. METHODS: This is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients. RESULTS: We included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %-3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %-8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08-0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events. CONCLUSIONS: Our findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS.

Regulation of Platelet Activation and Coagulation: Current Concepts, Novel Targets, and Therapies.

Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.

Antithrombotic Therapy in Patients with Complex Percutaneous Coronary Intervention and Cardiogenic Shock.

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Antithrombotic Therapy in Patients with Chronic Coronary Syndromes.

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.

Antithrombotic Therapy in Acute Coronary Syndrome.

Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies.

Considerations in Antiplatelet Therapy in Women Undergoing Treatment of Acute Coronary Syndrome or Percutaneous Coronary Intervention.

Antiplatelet therapy is integral to reduce the risk of future ischemic events following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI); this aim must be balanced by limiting the risk of bleeding. Women with ACS or undergoing PCI have distinct platelet physiology, vascular anatomy, and clinical profiles that can influence the selection of an appropriate regimen. There are procedural techniques that can enhance safety in women. The poor inclusion of women in ACS and PCI trials limits our understanding of the ideal antiplatelet regimen in women, and future studies must find ways to increase the participation of female patients.

Prior coronary stent does not exclude major pulmonary resection regardless of antiplatelet therapy.

PURPOSE: We assessed the safety of general thoracic surgery in patients with prior coronary stents undergoing lung resection, based on differences in perioperative antiplatelet therapy management. METHODS: We retrospectively examined 150 patients with coronary artery stents who underwent pulmonary resection between July 2009 and July 2018. The impact of the antiplatelet agent on thoracic surgery safety was assessed by comparing perioperative outcomes, including major adverse cardiac and cerebrovascular events, among the discontinued antiplatelet therapy (group D), heparin bridging (group H), and continuous antiplatelet therapy (group C) groups. RESULTS: Groups D, H, and C included twenty-four, eighty-four, and forty-two patients, respectively. Second-generation drug-eluting stents were used in > 50% of the patients. No significant differences were found in the estimated blood loss, transfusion rate, or operative duration. Major adverse cardiac and cerebrovascular events occurred in four (2.7%) patients, which was comparable among the groups. In group H, postoperative heart failure and transient ischemic attack with stroke occurred in one patient each. Major bleeding occurred in two (4.7%) patients in group C. CONCLUSIONS: Pulmonary resection surgical outcomes in patients with coronary artery stents were feasible regardless of antiplatelet therapy continuation. However, discontinuing dual-antiplatelet or single-antiplatelet therapy in such patients may be reasonable because this generation of drug-eluting stents has a higher safety profile than bare-metal and first-generation drug-eluting stents.

Accuracy and technical characteristics of CYP2C19 point of care tests: a systematic review.

Aim: To assess the accuracy and technical characteristics of CYP2C19 point of care tests (POCTs).Patients & methods: Systematic review of primary studies, in any population or setting, that evaluated POCTs for detecting CYP2C19 loss of function (LOF) alleles.Results: Eleven studies provided accuracy data (eight Spartan; one Genomadix Cube; one GMEX; one Genedrive). The POCTs had very high sensitivity and specificity for the alleles they tested for. Twenty-two studies reported technical characteristics: POCTs were easy to operate and provided results quickly. Limited data were reported for test failure rate and cost.Conclusion: CYP2C19 POCTs may be a useful alternative to laboratory-based testing to guide antiplatelet therapy. Further data are required on accuracy (GMEX; Genedrive), test failure and cost (all POCT).

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Heparin-like effect of a dual antiplatelet and anticoagulant (APAC) agent on red blood cell deformability and aggregation in an experimental model.

Treatments with different antithrombotic agents can affect micro-rheological variables, such as red blood cell (RBC) deformability and aggregation. Since the effect of dual antiplatelet and anticoagulant (APAC) treatment on micro-rheology is unknown, we aimed to investigate the effect of different intravenous doses of APAC on hematological and micro-rheological variables in a porcine model. Two groups were formed (APAC group, Control group), and blood was collected from the animals at preset intervals. Hematological variables, RBC deformability, and aggregation were measured. We observed an improvement in the RBC deformability measured at a low shear stress range (< 3 Pa). However, after both doses, a decrease in the maximal elongation index of RBC values occurred in the APAC group. RBC aggregation increased after APAC bolus dose, while it gradually and dose-dependently decreased. Supposedly, the improvement in RBC deformability that was observed at a lower shear rate could facilitate aggregation. Administration of APAC and unfractionated heparin (UFH) caused comparable changes in hematological and hemorheological variables. Signs of thrombosis or bleeding did not occur. APAC and UFH had comparable micro-rheological effects.

Does dutasteride reduce the bleeding in transurethral resection of the prostate in patients on antiplatelet drugs?

Background: The aim of this study was to assess the effect of a 4-week dutasteride treatment on reducing the intraoperative and postoperative bleeding, as well as the amount and duration of irrigation required to clear the urine after transurethral resection of the prostate (TURP) ≥50 g in men receiving the antiplatelet drug (APD). Materials and methods: This double-blind randomized clinical trial included patients with a prostate size ≥50 g who were indicated for TURP and were already receiving APD. The study was conducted in the Urology Department of Cairo University over a 12-month period. Routine preoperative laboratory investigations were performed in all patients. Moreover, baseline prostate size, serum prostate-specific antigen level, and International Prostate Symptom Score were estimated. The patients were randomly divided into 2 equal groups (groups A and B). Group A, the dutasteride group, received dutasteride (0.5 mg) once daily for 4 weeks. Group B, the placebo group, received a placebo capsule once daily for 4 weeks. Both groups underwent bipolar TURP. Fifteen patients were excluded from the study; 9 patients from group A and 6 patients from group B, either due to drug intolerability or loss follow-up. Results: The mean blood loss was insignificant between the 2 groups immediately after and 24 hours after surgery (Δ hemoglobin: 1.41 ± 0.63 g/dL vs. 1.48 ± 0.54 g/dL, 2.12 ± 0.70 g/dL vs. 2.31 ± 0.78 g/dL, respectively, p = 0.631, p = 0.333; Δ hematocrit: 2.97% ± 1.51% vs. 3.16% ± 1.36%, 4.96% ± 1.87% vs. 5.73% ± 4.39%, respectively, p = 0.610, p = 0.380). However, there were significant differences in duration of indwelling urethral catheter (5.10 ± 0.55 days vs. 5.80 ± 1.79 days, p = 0.048), duration of bladder irrigation (13.60 ± 2.85 hours vs. 16.33 ± 6.62 hours, p = 0.044), and the amount of saline used for bladder irrigation (11.03 ± 2.30 L vs. 13.87 ± 6.13 L, p = 0.046) between group A and group B. respectively. Conclusions: Treatment with dutasteride for 4 weeks before TURP in men receiving APD did not significantly reduce intraoperative or postoperative bleeding after TURP but could significantly reduce the duration of indwelling catheter placement, as well as the duration and amount of saline irrigation.

Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients.

BACKGROUND: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). OBJECTIVES: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. METHODS: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. RESULTS: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). CONCLUSIONS: The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.