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

https://doi.org/10.1016/j.jacc.2021.06.012Get rights and content
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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.

Key Words

clopidogrel
de-escalation
low-dose
network meta-analysis
prasugrel
systematic review
ticagrelor

Abbreviations and Acronyms

ACS
acute coronary syndrome
BARC
Bleeding Academic Research Consortium
DAPT
dual antiplatelet therapy
MI
myocardial infarction
PCI
percutaneous coronary intervention
RCT
randomized controlled trial
TIMI
Thrombolysis In Myocardial Infarction

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Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

Mahboob Alam, MBBS, served as Guest Associate Editor for this paper. Christie Ballantyne, MD, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs Shoji and Kuno contributed equally to this work.