De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes

J Am Coll Cardiol. 2021 Aug 24;78(8):763-777. doi: 10.1016/j.jacc.2021.06.012. Epub 2021 Jul 15.

Abstract

Background: Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent P2Y12 inhibitors has become a cornerstone of acute coronary syndrome (ACS) management. Recent randomized controlled trials (RCTs) have investigated DAPT de-escalation to decrease the risk of bleeding outcomes.

Objectives: The aim of this study was to compare the efficacy and safety outcomes of various DAPT strategies in patients with ACS, including de-escalation from a potent P2Y12 inhibitor to clopidogrel or low-dose prasugrel.

Methods: MEDLINE and EMBASE were searched through January 2021 for RCTs investigating the efficacy and safety of DAPT in patients with ACS, and a network meta-analysis was conducted. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding.

Results: Our search identified 15 eligible RCTs, including 55,798 patients with ACS. De-escalation therapy was associated with reduced risk of primary bleeding outcomes (HR: 0.48 [95% CI: 0.30-0.77] vs clopidogrel; HR: 0.32 [95% CI: 0.20-0.52] vs ticagrelor; HR: 0.36 [95% CI: 0.24-0.55] vs standard-dose prasugrel; and HR: 0.40 [95% CI: 0.22-0.75] vs low-dose prasugrel) without negatively affecting primary efficacy outcomes. There were no significant differences in ischemic or bleeding outcomes between de-escalation to clopidogrel or low-dose prasugrel.

Conclusions: Compared with other established uses of DAPT, de-escalation was the most effective strategy for ACS treatment, resulting in fewer bleeding events without increasing ischemic events.

Keywords: clopidogrel; de-escalation; low-dose; network meta-analysis; prasugrel; systematic review; ticagrelor.