Individualized or Uniform De-Escalation Strategies for Antiplatelet Therapy in Acute Coronary Syndrome: A Review of Clinical Trials with Platelet Function Testing and Genetic Testing-Based Protocols.

This comprehensive literature review assessed the effectiveness of precision medicine approaches in individualizing P2Y12 de-escalation strategies, such as platelet function testing guidance, genetic testing guidance, and uniform de-escalation, for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Analyzing six trials with a total of 13,729 patients, the cumulative analyses demonstrated a significant reduction in major adverse cardiac events (MACE), net adverse clinical events (NACE), and major and minor bleeding events with P2Y12 de-escalation. Specifically, the analysis found a 24% reduction of MACE and a 22% reduction of adverse event risk (relative risk (RR) 0.76, 95% confidence interval (CI): 0.71-0.82, and RR: 0.78, 95% CI 0.67-0.92, respectively). Reductions in bleeding events were highest with uniform unguided de-escalation, followed by guided de-escalations, while ischemic event rates were similarly lower across all three strategies. Although the review highlights the potential of individualized P2Y12 de-escalation strategies to offer a safer alternative to the long-term potent P2Y12 inhibitor-based dual antiplatelet therapy, it also indicates that laboratory-guided precision medicine approaches may not yet offer the expected benefits, necessitating further research to optimize individualized strategies and evaluate the potential of precision medicine approaches in this context.

Antithrombotic therapy for secondary prevention in patients with stroke or transient ischemic attack: A multiple treatment network meta-analysis of randomized controlled trials.

OBJECTIVE: As stroke represents one of the leading causes of mortality and disability worldwide, we aimed to determine the preventive effect of different antiplatelet therapies after an ischemic stroke or transient ischemic attack. METHODS: Network meta-analysis evaluating antiplatelet regimes after an ischemic stroke or transient ischemic attack. Searches were conducted in MEDLINE, EMBASE, and Cochrane Library databases until Nov. 23, 2021, for randomized controlled trials. Direct comparisons within trials were combined with indirect evidence from other trials by using a frequentist model. An additive network meta-analysis model was used to evaluate the influence of individual components. The primary efficacy endpoint was a recurrent stroke, the main safety outcomes were the risk of major bleeding and mortality at the longest available follow-up. RESULTS: 58 randomized controlled trials (175,730 patients) were analyzed. The analysis involved 20 antithrombotic strategies including different antiplatelet agents, combinations with aspirin, and anticoagulant therapies. Cilostazol proved to be the most efficacious in reducing stroke recurrence and the risk of bleeding (RR = 0.66, 95%CI = 0.55-0.80 and RR = 0.39, 95%CI = 0.08-2.01) compared to aspirin, respectively. Intensification with combinations of aspirin with ticagrelor or clopidogrel resulted in a lower risk of stroke recurrence (RR = 0.79, 95%CI = 0.67-0.93 and RR = 0.79, 95%CI = 0.72-0.87) but carried a higher bleeding risk (RR = 3.01, 95%CI = 1.65-5.49 and RR = 1.78 95%CI = 1.49-2.13). CONCLUSION: The prognosis of patients with an ischemic stroke or transient ischemic attack is improved with antiplatelets. Cilostazol showed the best risk-benefit characteristics without trade-off with the risk of major bleeding. Improved stroke recurrence with intensified antiplatelet regimens is counterbalanced with higher bleeding risk, and consequently, mortality remains unaffected. Treatment decisions in stroke survivals should integrate the assessment of bleeding risk for better identification of patients with the highest benefit of treatment intensification. SYSTEMATIC REVIEW REGISTRATION: Prospero registration number: CRD42020197143, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197143.

Antithrombotic Therapy for Secondary Prevention in Patients with Non-Cardioembolic Stroke or Transient Ischemic Attack: A Systematic Review.

Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification.