Bleeding Risk with Combination Antithrombotic Therapy: A Propensity-Score Matched Analysis

BackgroundLimited data exist on the safety of combining antiplatelets and anticoagulants (AC) for secondary stroke prevention in acute ischemic stroke (AIS). We sought to examine the hemorrhage risk with combining single (SAPT) or dual antiplatelet therapy (DAPT) with AC in AIS patients with concomitant atrial fibrillation (AF) and acute myocardial infarction (MI). MethodsThis retrospective cross-sectional cohort study used TriNetX, a federated health analytics database that collects real-time electronic health records data from 76 participating healthcare organizations in the United States. Through queries performed on March 31, 2023, adult patients with simultaneous diagnoses of AIS, AF and acute MI were identified using ICD-10 codes over the past 20 years. Propensity score-matched analysis, matching for demographics and vascular co-morbidities, compared the odds for acute spontaneous ICH and GI bleeding at 3-months, 12-months and throughout follow-up within TriNetX, between three matched sub-cohorts: AC alone, AC+SAPT, and AC+DAPT. ResultsAmong 144,434 AIS patients with AF and MI (mean age, 71.9 years; 43.3% female), 8772 (6.1%) patients received AC alone, 88,430 (61.2%) received AC+SAPT, and 47,232 (32.7%) received AC+DAPT. After propensity-score matching, 8,706 patients were included in each sub-cohort. Compared to AC alone, AC+SAPT and AC+DAPT showed no significant increase in ICH risk at 3 and 12 months but increased long-term risk throughout follow-up (odds ratio [95% confidence intervals] for AC+SAPT, 1.26 [1.11-1.44], p<0.001; for AC+DAPT, 1.34 [1.18-1.53], p<0.001). Gastrointestinal (GI) bleeding risk was elevated at all time-points with combination therapies. ConclusionWithin the limitations of a retrospective cross-sectional study using administrative data, this large propensity-score matched analysis demonstrates that combining antiplatelets with anticoagulants after AIS may be associated an increased risk of ICH only in the long-term, beyond 12-months, but with an increased risk of acute GI bleeding in the short and long-term. Larger prospective studies are warranted to confirm our findings.