High-intensity versus Low- or Moderate-intensity Statin Treatment for Patients with Ischemic Stroke: Nationwide Cohort Study

Background: Guidelines recommend high-intensity statin treatment after ischemic stroke, but knowledge on the effectiveness and safety for different statin intensities remains sparse.

Objectives: To examine effectiveness and safety outcomes among patients initiating high-intensity versus low- or moderate-intensity statins after ischemic stroke.

Methods: In this Danish population-based, new-user, active-comparator cohort study, we used the Danish Stroke Registry to identify patients with a first-time ischemic stroke during 2012-2018. Patients redeeming a prescription for a high-intensity or low- or moderate-intensity statin within 21 days after the admission were identified. Inverse probability of treatment weighting was used to balance patient characteristics between cohorts. We used competing risk methods to compute 5-year risk differences (RDs) and Cox regression to compute hazard ratios (HRs) of stroke recurrence, myocardial infarction, heart failure, venous thromboembolism, peripheral artery disease, and all-cause mortality (effectiveness outcomes) and diabetes, cancer, liver disease, and kidney disease (safety outcomes).

Results: High (n=5,770) and low- or moderate (n=12,052) intensity statin initiators were identified. Risks of most examined effectiveness outcomes were comparable between statin groups. For example, the 5-year RDs and HRs, comparing high- with low- or moderate-intensity, were 1.3% (95% Confidence intervals: 0.3, 2.2) and 1.14 (95% CI: 0.95, 1.38) for stroke recurrence and 0.3% (95% CI: -0.1, 0.8) and 1.08 (95% CI: 0.70, 1.66) for myocardial infarction. A noticeable exception was all-cause mortality, which was reduced (RD: -2.9% [95% CI: -4.4, -1.5], HR: 0.83 (95% CI: 0.71, 0.97]). Risks of most safety outcomes were comparable between statin intensity groups, despite high-intensity statin use was associated with a slightly increased risk of diabetes (RD: 1.5 [95% CI: 0.4, 2.6], HR: 1.17 [95% CI: 1.02, 1.35]).

Conclusions: Initiation of high-intensity statins after ischemic stroke was associated with similar risks of most effectiveness and safety outcomes as initiation of low- or moderate-intensity statins, including stroke recurrence. Yet, mortality risk was reduced, and diabetes risk was slightly increased.