Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

• Published in: JAMA : the journal of the American Medical Association 2020-10, Vol.324 (16), p.1640-1650
• Main Authors: You, Seng Chan, Rho, Yeunsook, Bikdeli, Behnood, Kim, Jiwoo, Siapos, Anastasios, Weaver, James, Londhe, Ajit, Cho, Jaehyeong, Park, Jimyung, Schuemie, Martijn, Suchard, Marc A, Madigan, David, Hripcsak, George, Gupta, Aakriti, Reich, Christian G, Ryan, Patrick B, Park, Rae Woong, Krumholz, Harlan M
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - mortality; Acute Coronary Syndrome - surgery; Acute coronary syndromes; Adult; Aged; Aged, 80 and over; Algorithms; Angioplasty; Aspirin; Aspirin - administration & dosage; Bleeding; Case-Control Studies; Cause of Death; Cerebral infarction; Clinical medicine; Clopidogrel; Clopidogrel - administration & dosage; Clopidogrel - adverse effects; Databases, Factual - statistics & numerical data; Dyspnea; Dyspnea - chemically induced; Electronic health records; Electronic medical records; Female; Hemorrhage; Hemorrhage - chemically induced; Humans; Ischemia; Ischemia - chemically induced; Male; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - epidemiology; Network Meta-Analysis; Original Investigation; Percutaneous Coronary Intervention; Propensity Score; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - adverse effects; Recurrence; Republic of Korea; Respiration; Retrospective Studies; Risk; Stroke; Stroke - epidemiology; Systematic review; Ticagrelor - administration & dosage; Ticagrelor - adverse effects; United States
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2020.16167

IMPORTANCE: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention. OBJECTIVE: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record–based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019. EXPOSURES: Ticagrelor vs clopidogrel. MAIN OUTCOMES AND MEASURES: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis. RESULTS: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P