Antithrombotic therapy and cardiovascular outcomes after transcatheter aortic valve implantation in patients without indications for chronic oral anticoagulation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. METHODS AND RESULTS: We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41-0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67-1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32-1.14 and RR 0.59, 95% CI 0.34-1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29-0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25-0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16-0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. CONCLUSION: Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study.

Compared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 microM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.