Short dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk patients: Systematic review and meta-analysis

PLOS ONE RESEARCH ARTICLE Short dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk patients: Systematic review and meta-analysis Kevin R. Bainey1, Guillaume Marquis-Gravel2, Blair J. MacDonald ID3, David Bewick4, Andrew Yan5, Ricky D. Turgeon ID3* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, 2 Montreal Heart Institute, Université de Montréal, Montreal, Quebec, 3 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, 4 New Brunswick Heart Center, Horizon Health Network, Saint John, New Brunswick, 5 Division of Cardiology, Canadian Heart Research Centre and Terrence Donnelly Heart Centre, St Michael’s Hospital, University of Toronto, Toronto, Ontario * OPEN ACCESS Citation: Bainey KR, Marquis-Gravel G, MacDonald BJ, Bewick D, Yan A, Turgeon RD (2023) Short dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk patients: Systematic review and metaanalysis. PLoS ONE 18(9): e0291061. https://doi. org/10.1371/journal.pone.0291061 Editor: R. Jay Widmer, Baylor Scott and White, Texas A&M College of Medicine, UNITED STATES Received: March 6, 2023 Abstract Introduction Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces major adverse cardiovascular events (MACE) and stent thrombosis. However, DAPT duration is a concern in high bleeding risk (HBR) patients. We evaluated the effect of short DAPT (1–3 months) compared to standard DAPT (6–12 months) on bleeding and ischemic events in HBR PCI. Methods Accepted: August 21, 2023 Published: September 1, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0291061 Copyright: © 2023 Bainey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. We searched MEDLINE, Embase and CENTRAL up to August 18, 2022. Randomized controlled trials (RCTs) comparing short DAPT (1–3 months) versus standard DAPT in HBR PCI were included. We assessed risk of bias (RoB) using the Cochrane RoB2 tool, and certainty of evidence using GRADE criteria. Outcomes included MACE, all-cause death, stent thrombosis, major bleeding, and the composite of major or clinically-relevant non-major bleeding. We estimated risk ratios (RR) and 95% confidence intervals (CI) using a randomeffects model. Results From 503 articles, we included five RCTs (n = 7,242) at overall low risk of bias with median follow-up of 12-months. Compared to standard DAPT, short DAPT did not increase MACE (RR 1.02, 95% CI 0.84–1.23), all-cause death (RR 0.92, 95% CI 0.71–1.20) or stent thrombosis (RR 1.47, 95% CI 0.73–2.93). Short DAPT reduced major bleeding (RR 0.34, 95% CI 0.13–0.90) and the composite of major or clinically-relevant non-major bleeding (RR 0.60, 95% CI 0.44–0.81), translating to 21 and 34 fewer events, respectively, per 1000 patients. PLOS ONE | https://doi.org/10.1371/journal.pone.0291061 September 1, 2023 1 / 12 PLOS ONE Funding: This work was conducted to support the Canadian Cardiovascular Society Antiplatelet Guidelines with funding provided to Ricky Turgeon by the Canadian Cardiovascular Society (https:// ccs.ca/). The funder did not play any role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript. Short DAPT duration after PCI in high bleeding risk patients Conclusions In HBR PCI, DAPT for 1–3 months compared to 6–12 months reduced clinically-relevant bleeding events without jeopardizing ischemic risk. Short DAPT should be considered in HBR patients receiving PCI. Competing interests: The authors have declared that no competing interests exist. Introduction Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces the risk of stent thrombosis and protects from non-culprit atherothrombotic events long-term. The 2018 Canadian Cardiovascular Society (CCS)/Canadian Association of Interventional Cardiology (CAIC) Focused Update for the Use of Antiplatelet Therapy recommend DAPT with low-dose aspirin and a P2Y12 receptor inhibitor for 1 year (and up to 3 years in low bleeding / high ischemic risk patients) in acute coronary syndromes (ACS) and a minimum of 6 months (and up to 1 year) in non-ACS patients following PCI [1]. Subsequent studies in the era of use of newer-generation drug-eluting stents (DES), which have reduced risk of stent thrombosis, have suggested that DAPT may be safely be reduced to 6 months without increasing thrombotic risk [2–4]. More recently, this threshold has been further reduced with randomized studies supporting shortened DAPT of 1 to 3 months following PCI regardless of ACS presentation using mainly P2Y12 inhibitor single antiplatelet therapy (SAPT) [5–10]. Standard (and prolonged) DAPT protects against thrombotic events, yet major bleed following PCI is associated with a 3 to 5-fold risk of mortality, which offsets this protective benefit [11]. In this context, identifying patients at high bleeding risk (HBR) may help tailor DAPT duration recommendations [12]. The Academic Research Consortium (ARC) have created a definition for HBR that includes major a minor risk criteria, with patients being classified as HBR if they fulfill at least 1 major or 2 minor criteria [13]. This HBR definition is associated with a 1-year risk of a Bleeding Academic Research Consortium (BARC) category 3 or 5 bleed �4% or intracranial hemorrhage (ICH) of �1%. We performed a systematic review and meta-analysis of randomized studies in HBR patients receiving PCI with DES to determine whether short DAPT duration of 1 to 3 months followed by SAPT compared to standard DAPT duration of �6 months reduces the risk of major bleeding without compromising ischemic events. Methods We performed a systematic review and meta-analysis according to the methodology outlined in the Cochrane Handbook for Systematic Reviews and Interventions using a prospectivelydesigned (but not registered) protocol, and reported following the 2020 PRISMA statement [11]. Search strategy We searched MEDLINE (inception to August 18, 2022), Embase (January 1, 2019 to August 18, 2022), and the Cochrane Central Register of Controlled Trials (CENTRAL; January 1, 2019 to August 18, 2022) using the search strategies described in the S1 Appendix. We further supplemented this with a Web of Science (...truncated)