Prasugrel 10mg tablets

Background and aimsClopidogrel may be a less effective antiplatelet agent for secondary prevention after cardiovascular events in carriers of the CYP2C19 Loss of Function (LoF) allele. Randomized controlled trials (RCTs) of clopidogrel in patients with known CYP2C19 carrier status have provided inconsistent results. This meta-analysis aims to pool evidence on the effect of different antiplatelet strategies on outcomes according to CYP2C19 LoF status.MethodsWe conducted a systematic review and meta-analysis of RCTs to evaluate the interaction of CYP2C19 LoF allele on clopidogrel versus placebo or other antiplatelet agents in patients with cardiovascular disease or transient ischemic attack (TIA) or ischemic stroke. Primary outcomes were major adverse cardiovascular events (MACEs) including ischemic stroke, with major bleeding events assessed as a safety outcome. Random effects analysis estimated pooled odds ratios for LoF carriers and non-carriers.ResultsFifteen RCTs with 35,189 participants in total were included. When all interaction effects are pooled, the occurrence of MACE was 1.29 times higher in LoF variant carriers compared to non-carriers for clopidogrel treatment (p-interaction = 0.01). Risk of MACE was 1.20 times higher in LoF carriers compared to non-carriers when clopidogrel was compared to placebo (p-interaction = 0.13). In TIA or minor stroke patients, the interaction effect was 1.63 times larger (p-interaction = 0.02). Clopidogrel was less effective than prasugrel for MACE occurrence (1.57 times higher, p-interaction = 0.02) and ticagrelor (1.21 times higher, p-interaction = 0.19) in CYP2C19 LoF variant carriers. Bleeding outcomes were similar across groups.ConclusionClopidogrel is less effective in patients with CYP2C19 LoF genotype and cardiovascular disease, minor stroke, or TIA. The size and direction of the interaction warrant further research into the role of LoF genotypes and the cost-effectiveness of genetic testing. Prasugrel may be a more effective alternative for CYP2C19 LoF carriers.Registration-URL:https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021242993.

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Low-dose prasugrel could provide a better balance between adverse ischemic and bleeding events compared to other P2Y12 receptor inhibitors as part of dual antiplatelet therapy (DAPT) for patients with ischemic heart disease. This study evaluated these risks of adverse events associated with low-dose prasugrel and other P2Y12 receptor inhibitors. A network meta-analysis was conducted, searching for randomized controlled trials (RCTs) comparing clopidogrel (75 mg), low-dose (3.75 mg) and standard-dose (10 mg or 5 mg) prasugrel, or ticagrelor (180 mg). The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. The secondary endpoint was major bleeding, cardiovascular death, myocardial infarction, and stroke. Across 13 RCTs, neither low-dose prasugrel, standard-dose prasugrel, nor ticagrelor showed a statistically significant difference in MACE compared to clopidogrel [risk ratio (RR): 0.73, 95% confidence interval (CI) 0.49-1.09; RR: 0.86, 95% CI 0.68-1.09; RR: 1.02, 95% CI 0.62-1.67, respectively]. However, the standard dose of prasugrel was associated with a significantly higher risk of bleeding events compared to clopidogrel (RR, 0.72; 95% CI 0.35-1.49; RR, 1.26; 95% CI 1.01-1.58; RR, 1.26; 95% CI 0.82-1.96). The surface under the cumulative ranking curves was highest for low-dose prasugrel for both MACE and bleeding events (17.3 and 64.6 for clopidogrel, 84.5 and 84.9 for low-dose prasugrel, 62.0 and 11.8 for standard-dose prasugrel, and 36.2 and 38.7 for ticagrelor, respectively). Low-dose prasugrel may be a viable option in addition to standard P2Y12 receptor inhibitors.

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BACKGROUND: Clopidogrel is the guideline-recommended P2Y12 inhibitor for dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in Chronic Coronary Syndrome (CCS). Recent evidence suggests potential benefits of more potent P2Y12 inhibitors, primarily Ticagrelor, though their role in CCS remains less defined than in acute settings. OBJECTIVE: To compare the efficacy and safety of Ticagrelor or Prasugrel with Clopidogrel in DAPT following PCI in CCS patients. METHODS: A systematic approach was used to identify eligible randomized controlled trials (RCTs) and observational studies comparing the safety and efficacy of Ticagrelor or Prasugrel versus Clopidogrel. A meta-analysis using a random-effects model evaluated major adverse cardiovascular events (MACE), its individual components, and bleeding outcomes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by study design, P2Y12 inhibitor type, follow-up duration, and geographical region. RESULTS: Twelve studies (6 RCTs, 6 observational) were included, comprising 10,048 patients receiving potent P2Y12 inhibitors (Ticagrelor: 10 studies; Prasugrel: 3 studies) and 45,103 receiving Clopidogrel. Potent P2Y12 inhibitors were associated with a significantly reduced risk of MACE (OR = 0.69, 95% CI: 0.55–0.88) and all-cause mortality (OR = 0.63, 95% CI: 0.46–0.88). These benefits were primarily driven by the Ticagrelor subgroup, observational data, follow-up > 6 months, and Asian studies. While no significant differences were found for myocardial infarction, stroke, or overall stent thrombosis, the Ticagrelor subgroup showed a significantly lower risk of revascularization (OR = 0.67, 95%CI: 0.52–0.86). Regarding safety, while major bleeding showed a non-significant trend toward increase (OR = 1.41, 95% CI: 0.92–2.17), minor bleeding was significantly higher in the potent P2Y12 group (OR = 1.56, 95% CI: 1.26–1.95). CONCLUSION: This meta-analysis suggests that intensified DAPT, primarily Ticagrelor-based, may offer superior clinical benefit to Clopidogrel-based DAPT in patients with CCS undergoing PCI, particularly by reducing MACE, all-cause mortality, and revascularization. However, these benefits are accompanied by an increased risk of minor bleeding and a potential signal toward higher major bleeding. Considering the scarcity of large-scale RCTs, heterogeneous MACE definitions, limited data on Prasugrel, and ethnic/racial influence on bleeding risk and thrombotic events, these findings emphasize the need for individualized post-PCI antiplatelet regimens and support further long-term RCTs to better define the role of potent P2Y12 inhibitors in this population.

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