Thrombotic and ischemic event reporting with anticoagulant reversal agents: a multi-agent FAERS pharmacovigilance...

Anticoagulant reversal is usually performed during severe bleeding in patients who may remain at substantial thrombotic risk. We evaluated thrombotic and ischemic adverse-event reporting for andexanet alfa, idarucizumab, and a prothrombin complex concentrate (PCC) exposure set in the FDA Adverse Event Reporting System (FAERS). Public quarterly FAERS ASCII files from 2018Q2 through 2026Q1 were analyzed according to reporting principles for disproportionality analyses. Reports were deduplicated at case level. The primary exposure definition was primary or secondary suspect (PS/SS) reversal-agent reporting; all-role exposure, core-endpoint, and product/formulation-specific PCC analyses were sensitivity analyses. Exact Medical Dictionary for Regulatory Activities (MedDRA) preferred-term dictionaries defined thrombotic and ischemic endpoints. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and information component lower bounds (IC025) were calculated. The dataset included 11,586,364 deduplicated reports. PS/SS exposure sets included 1,086 andexanet alfa, 1,163 idarucizumab, and 1,080 PCC reports. The thrombotic/ischemic composite was reported in 371 andexanet reports (ROR 32.72, 95% CI 28.87-37.10), 156 idarucizumab reports (ROR 9.78, 95% CI 8.26-11.57), and 231 PCC reports (ROR 17.16, 95% CI 14.84-19.85). Ischemic stroke was the strongest andexanet component signal (ROR 120.38, 95% CI 103.88-139.49). FAERS reports showed disproportionate thrombotic and ischemic reporting for all three reversal-agent exposure sets, with a prominent andexanet signal for ischemic stroke. These findings are hypothesis-generating and should not be interpreted as incidence, causality, or a direct comparative clinical-risk estimate.