Existing clinical evidence hasn’t determined a superior therapy for CAD/VAD. The CADISS randomized trial reported no clear difference between strategies, whereas subsequent work, including the open-label TREAT-CAD trial, suggested aspirin didn’t meet noninferiority versus vitamin K antagonists. The therapeutic landscape has further diversified with the advent of direct oral anticoagulants (DOAC), for which comparative data remain largely observational and heterogeneous.

We queried TriNetX to identify patients with a diagnosis of CAD or VAD. Patients were stratified into three groups using recorded medication codes within a month of the dissection diagnosis: antiplatelet agents, warfarin, and DOACs. The index date was the first use of medication. Patients who crossed over to any other study drug and those with intracranial hemorrhage within 7 days before the index medication were excluded. We performed 1:1 propensity-score matching on 15 prespecified covariates spanning outcome-related factors. Cox proportional-hazards models were used to estimate hazard ratios for outcomes during 90 and 180 days of follow-up. Outcomes of interest were (1) brain or other organ hemorrhage; (2) all-cause mortality; (3) hospitalization; (4) use of critical care service; (5) emergency department visit; (6) repeat procedure for CAD/VAD; and (7) recurrent stroke or transient ischemic attack (TIA).

Among 26,703 antiplatelet users, 1,266 on DOACs, and 1,548 on warfarin, antiplatelets were associated with higher adverse outcomes than either anticoagulant. Compared with DOACs, warfarin showed higher all-cause mortality and hospitalization. Over long-term follow-up, antiplatelets had the lowest risk of recurrent stroke or TIA versus either anticoagulant but a higher risk of all-cause mortality.

Anticoagulants may have a more favorable safety profile, but confirmatory observational studies and randomized trials are warranted.