Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis

Joseph S Hudson; Kamil W Nowicki; Brandon Lucke-Wold; Zachary C Gersey; William S Dodd; Ali Alattar; David J McCarthy; Prateek Agarwal; Zain Mehdi; Michael J Lang; David M Hasan; Brian L Hoh; Bradley A Gross

doi:10.1007/s12975-023-01179-9

Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis

Transl Stroke Res. 2023 Jul 20. doi: 10.1007/s12975-023-01179-9. Online ahead of print.

Affiliations

¹ Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, 4th floor, Pittsburgh, PA, USA. hudsonjs@upmc.edu.
² Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, 4th floor, Pittsburgh, PA, USA.
³ Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, FL, USA.
⁴ University of Iowa Carver College of Medicine, Iowa City, IA, USA.
⁵ Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.

PMID: 37470917
DOI: 10.1007/s12975-023-01179-9

Abstract

Maladaptive inflammation underlies the formation and rupture of human intracranial aneurysms. There is a growing body of evidence that anti-inflammatory pharmaceuticals may beneficially modulate this process. Clopidogrel (Plavix) is a commonly used irreversible P2Y12 receptor antagonist with anti-inflammatory activity. In this paper, we investigate whether clopidogrel is associated with the likelihood of aneurysm rupture in a multi-institutional propensity-matched cohort analysis. Patients presenting for endovascular treatment of their unruptured intracranial aneurysms and those presenting with aneurysm rupture between 2015 and 2019 were prospectively identified at two quaternary referral centers. Patient demographics, comorbidities, and medication usage at the time of presentation were collected. Patients taking clopidogrel or not taking clopidogrel were matched in a 1:1 fashion with respect to location, age, smoking status, aneurysm size, aspirin usage, and hypertension. A total of 1048 patients with electively treated aneurysms or subarachnoid hemorrhages were prospectively identified. Nine hundred twenty-one patients were confirmed to harbor aneurysms during catheter-based diagnostic angiography. A total of 172/921 (19%) patients were actively taking clopidogrel at the time of presentation. Three hundred thirty-two patients were matched in a 1:1 fashion. A smaller proportion of patients taking clopidogrel at presentation had ruptured aneurysms than those who were not taking clopidogrel (6.6% vs 23.5%, p < .0001). Estimated treatment effect analysis demonstrated that clopidogrel usage decreased aneurysm rupture risk by 15%. We present, to the best of our knowledge, the first large-scale multi-institutional analysis suggesting clopidogrel use is protective against intracranial aneurysm rupture. It is our hope that these data will guide future investigation, revealing the pathophysiologic underpinning of this association.

Keywords: Aneurysm; Clopidogrel; Inflammation; Stroke; Subarachnoid hemorrhage.