Abstract

Background Limited 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).

Methods This 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.

Results Among 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.

Conclusion Within 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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

This was a retrospective study.

Funding Statement

No funding was provided.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the IRB department of UAMS.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

The data is available and accessible on TrinetX.

Non-standard Abbreviations and AcronymsAFAtrial fibrillationACAnticoagulationASCVDAtherosclerotic cardiovascular diseaseDAPTDual anti-platelet therapyICHIntra-cerebral hemorrhagePCIPercutaneous coronary interventionSAPTSingle anti-platelet therapySIHDStable ischemic heart disease