Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study

Abstract

Background: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period.

Methods and results: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis.

Conclusions: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage.

Registration: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Keywords: China; follow‐up studies; hydroxymethylglutaryl‐CoA reductase inhibitors; intracranial hemorrhages; ischemic stroke; prospective studies.

Figure 1. Flow chart illustrating the inclusion and exclusion of patients.

Figure 2. Kaplan–Meier curves for stroke and intracranial hemorrhage.

A, Cumulative probability of stroke at 3‐mo; B, Cumulative probability of stroke at 12‐mo; C, Cumulative probability of intracranial hemorrhage at 3‐mo; D, Cumulative probability of intracranial hemorrhage at 12‐mo. The colored areas around the solid lines indicate 95% CIs. ICH indicates intracranial hemorrhage.

Figure 3. Forest plot of risk of recurrent stroke by subgroup analyses at 3 months.

Adjusted for age, male sex, modified Rankin Scale score >0 prestroke, use of DAPT, arrival National Institutes of Health Stroke Scale score, low‐density lipoprotein cholesterol, total cholesterol, systolic blood pressure, onset to treatment time, TOAST classification, history of diabetes, history of hyperlipidemia, history of transient ischemic attack, history of atrial fibrillation, history of ischemic stroke. DAPT indicates dual antiplatelet therapy with clopidogrel plus aspirin; HIS group, high‐intensity statins group; HR, hazard ratio for high–dose vs moderate‐dose; LAA, large artery atherosclerosis; MIS group, moderate‐intensity statins group; OE, other determined cause; SVO, small vessel occlusion; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; and UE, undetermined cause. P value by a Cox subgroup analysis model.