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. 2020 Oct 13;142(15):1425-1436.
doi: 10.1161/CIRCULATIONAHA.120.046308. Epub 2020 Aug 3.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis

Safi U Khan  1 , Maninder Singh  2 , Shahul Valavoor  1 , Muhammad U Khan  1 , Ahmad N Lone  1 , Muhammad Zia Khan  1 , Muhammad Shahzeb Khan  3 , Preethi Mani  4 , Samir R Kapadia  4 , Erin D Michos  5 , Gregg W Stone  6 , Ankur Kalra #  4   7 , Deepak L Bhatt #  8
Affiliations

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis

Safi U Khan et al. Circulation. .

Abstract

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents.

Methods: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model.

Results: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding.

Conclusions: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

Keywords: drug-eluting stents; dual anti-platelet therapy; network meta-analysis; percutaneous coronary intervention.

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Conflict of interest statement

Dr Bhatt discloses the following relationships: Advisory Board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portopulmonary Hypertension Treatment With Macitantan: a Randomized Clinical Trial], funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial [CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement], funded by Edwards), Contego Medical (Chair, PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial [Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation], funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; REDUAL PCI clinical trial (Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) steering committee funded by Boehringer Ingelheim; AEGIS-II (Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome) executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (continuing medical education steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, Takeda. Dr Stone discloses the following relationships: speaker or other honoraria from Cook, Terumo, QOOL Therapeutics and Orchestra Biomed; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, Valfix. Dr Singh discloses the following relationships: Minor-Reimbursement from C3 Interventional Academy, Abiomed and Siemens for attending a conference and workshop. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Network of DAPT interventions. The area of the circles is based on the total number of patients for each treatment among all trials. The thickness of the lines is based on the total number of studies comparing the 2 treatments. DAPT indicates dual antiplatelet therapy.
Figure 2.
Figure 2.
Network meta-analyses for myocardial infarction and major bleeding. Midterm [aspirin] represents discontinuation of DAPT at midterm followed by continuation of aspirin. Short-term [aspirin] represents discontinuation of DAPT at short term followed by continuation of aspirin. Short-term [P2Y12 inhibitor] represents discontinuation of DAPT at short term followed by continuation of P2Y12 inhibitor. Absolute risk differences are reported as incident cases per 1000 person-years. DAPT indicates dual antiplatelet therapy; RD, risk difference; and RR, risk ratio.
Figure 3.
Figure 3.
Net clinical benefit. Risk ratios of different DAPT strategies in comparison with 12-month DAPT (reference) and associated 95% confidence intervals are plotted. Major bleeding is on the x axis and myocardial infarction is on the y axis. A and B represent comparison in total cohort and acute coronary syndrome cohort, respectively. DAPT indicates dual antiplatelet therapy; and RR, risk ratio.
Figure 4.
Figure 4.
Network meta-analyses for secondary end points. Midterm [aspirin] represents discontinuation of DAPT at midterm followed by continuation of aspirin. Short-term [aspirin] represents discontinuation of DAPT at short term followed by continuation of aspirin. Short-term [P2Y12 inhibitor] represents discontinuation of DAPT at short term followed by continuation of P2Y12 inhibitor. Absolute risk differences are reported as incident cases per 1000 person-years. DAPT indicates dual antiplatelet therapy; MACE, major adverse cardiovascular events; NACE, net adverse clinical events; RD, risk difference; and RR, risk ratio.
Figure 5.
Figure 5.
Rankograms for clinical outcomes. Mid-term [aspirin] represents discontinuation of dual antiplatelet therapy at midterm followed by continuation of aspirin. Short-term [aspirin] represents discontinuation of dual antiplatelet therapy at short term followed by continuation of aspirin. Short-term [P2Y12 inhibitor] represents discontinuation of dual antiplatelet therapy at short term followed by continuation of P2Y12 inhibitor. MACE indicates major adverse cardiovascular events; and NACE, net adverse clinical events.
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