Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis

Abstract

Objectives: The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.

Background: The role of abbreviated DAPT followed by an oral P2Y12 inhibitor after PCI remains uncertain.

Methods: Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.

Results: Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p < 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p < 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar.

Conclusions: Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

Keywords: DAPT; P2Y(12) inhibitors; aspirin; meta-analysis; ticagrelor.

Conflict of interest statement

Funding Support and Author Disclosures This study was funded by institutional support from the Department of Cardiology at Bern University Hospital. Dr. Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia Pharmaceuticals, Universität Basel Departement Klinische Forschung, Vifor, Bristol Myers Squibb, iVascular, and Medscape; and has received grants and personal fees from Terumo, , outside the submitted work. Dr. Mehran has received grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco d/b/a PLx Pharma, Roivant Sciences, Sanofi, Medtelligence, and Janssen Scientific Affairs; has received other from Abbott Laboratories, Abiomed, The Medicines Company, Spectranetics/Philips/Volcano, Bristol Myers Squibb, and Watermark Research Partners; and has received nonfinancial support and other from Regeneron Pharmaceuticals, outside the submitted work. Dr. Baber has received grants and personal fees from AstraZeneca; and has received personal fees from Boston Scientific and Amgen, outside the submitted work. Dr. Heg is affiliated with CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. For an up-to-date list of CTU Bern’s conflicts of interest see http://www.ctu.unibe.ch/research/declaration_of_interest/index_eng.html. Dr. Windecker has received research and educational grants to the institution from Abbott, Amgen, Bayer, Bristol Myers Squibb, Biotronik, Boston Scientific, CSL Behring, Edwards Lifesciences, Medtronic, Polares, and Sinomed, outside the submitted work. Dr. Vranckx has received personal fees from AstraZeneca, Daiichi-Sankyo, Bayer, CLS Behring, and Medscape, outside the submitted work. Dr. Gibson has received grants and personal fees from AstraZeneca, during the conduct of the study; has received grants and personal fees from Angel Medical Corporation, Bayer, CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson, Portola Pharmaceuticals; has received personal fees from The Medicines Company, Boston Clinical Research Institute, the Cardiovascular Research Foundation, Eli Lilly, Gilead Sciences, Novo Nordisk, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, St. Francis Hospital, Verreseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio, MedImmune, Medtelligence, Microport, PERT Consortium, GE Healthcare, Caladrius Bioscience, CeleCor Therapeutics, and Thrombolytic Science; has received other from nference; has received nonfinancial support from Baim Institute; has received grants from Bristol Myers Squibb, SCAD Alliance, outside the submitted work. Dr. Leonardi has received grants and personal fees from AstraZeneca; and has received personal fees from Bayer and Bristol Myers Squibb/Pfizer, outside the submitted work. Dr. Angiolillo has received grants and personal fees from Amgen, Aralez, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, Sanofi, CeloNova, St. Jude Medical, and AstraZeneca; has received personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, and The Medicines Company; and has received grants from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals, Matsutani Chemical Industry, Novartis, Osprey Medical, Renal Guard Solutions, the Scott R. MacKenzie Foundation, the National Institutes of Health/National Center for Advancing Translational Sciences (Clinical and Translational Science Award to the University of Florida, UL1 TR000064), and the National Institutes of Health/National Human Genome Research Institute (U01 HG007269), outside the submitted work. Dr. Liebetrau has received personal fees from AstraZeneca, outside the submitted work. Dr. Steg has received grants and personal fees from Bayer/Janssen, Merck, Sanofi, Amarin, and Servier; and has received personal fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Novartis, Regeneron, Eli Lilly, AstraZeneca, and Idorsia, outside the submitted work. Dr. Dudek has received grants and personal fees from AstraZeneca, outside the submitted work. Dr. Mehta has received grants from Boston Scientific, Abbott Vascular, and Sanofi, outside the submitted work. Dr. McFadden has received personal fees from the University of Bern, during the conduct of the study. Dr. Oldroyd has received personal fees from Abbott Vascular and Biosensors; and has received grants and personal fees from Boston Scientific, outside the submitted work. Dr. Kunadian has received personal fees from Abbott Vascular, Bayer, Amgen, and Daichii-Sankyo; and has received grants from AstraZeneca, outside the submitted work. Dr. Dangas has received grants and personal fees from Abbott Vascular, Boston Scientific, and AstraZeneca; and has received personal fees from Biosensors and Sanofi, outside the submitted work. Dr. Pocock has received personal fees from AstraZeneca, during the conduct of the study. Dr. Jüni serves as an unpaid member of the steering groups of trials funded by AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; has received research grants to the institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company; and has received honoraria to the institution for participation in advisory boards and/or consulting from Amgen, Ava, and Fresenius; but has not received personal payments from any pharmaceutical company or device manufacturer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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