Abstract 27: Statin use and risk of hemorrhagic stroke in a community-based cohort of aging women: The Women’s Health Initiative
Authors: Salmoirago-Blotcher Elena , Hovey Kathleen M , Ockene Judith K , Andrews Chris A , Robinson Jennifer , Johnson Karen C , Smoller Sylvia , Martin Lisa W , Qi Lihong , Crawford Sybil , Ockene Ira S , Manson JoAnne E 
Published: July 2021

Background:
Statin therapy is recommended for treatment of hypercholesterolemia and prevention of cardiovascular events. Concerns have been raised about a potentially higher risk of hemorrhagic stroke in statin users; however, there is limited information in women and in older populations. We evaluated whether statin treatment was associated with increased risk of hemorrhagic stroke among women enrolled in the Women’s Health Initiative (WHI).

Methods:
This secondary data analysis was conducted among 68,132 women enrolled in the WHI Clinical Trials (CTs). Participants were 50 to 79 yrs old; postmenopausal; and were followed through 2005 (parent study) and for an additional 5 yrs (through September 30, 2010) in the WHI extension study. Statin use was assessed at baseline and at follow-up (FU) visits at 1, 3, 6, and 9 years. Women brought all medications in original containers for inventory. Strokes were self-reported annually and adjudicated by medical record review. Risk of hemorrhagic stroke by statin use (modeled as a time-varying covariate, with the “no use” category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for hemorrhagic stroke (model 2); and possible confounders by indication (model 3). All models adjusted for enrollment in the different CTs and in the extension study. Participants were censored at the date of last contact or loss to FU. Pre-specified subgroup analyses were conducted according to use or non-use of antiplatelet medications (including aspirin) or anticoagulants, and prior history of stroke.

Results:
Final models included 67,882 women (mean age at baseline 63 ± 7 yrs). Over a mean FU of 12 yrs, incidence rates of hemorrhagic stroke were 6.4/10,000 person-years among women on statins and 5.0/10,000 person-years among women not taking statins. The unadjusted risk of hemorrhagic stroke in statin users vs. non-users was 1.21 (CI: 0.96, 1.53). The HR was attenuated to 0.98 (CI: 0.76, 1.26) after adjusting for age, hypertension, and other risk factors for hemorrhagic stroke. Planned subgroups analyses showed that women taking both statins and antiplatelet agents had a higher risk of hemorrhagic stroke than women taking antiplatelet medications without statins (HR: 1.59; CI: 1.02, 2.46), whereas women not taking antiplatelet medications had no risk elevation with statins (HR=0.79; CI: 0.58-1.08); P for interaction = .01. No significant interactions were found for anticoagulant use or prior history of stroke, but the statistical power for these analyses was low.

Conclusion:
Statin use was not associated with an overall increased risk of hemorrhagic stroke among older community-dwelling women. However, women taking statins in conjunction with antiplatelet medications had elevated risk; a finding that warrants further study and potential incorporation into clinical decision making.