By Matthew E. Fink, MD

Feil Professor and Chairman, Department of Neurology, and Assistant Dean of Clinical Affairs, Weill Cornell Medical College; Neurologist-in-Chief, New York Presbyterian Hospital

Dr. Fink reports no financial relationships relevant to this field of study.

SOURCE: Bosch J, Lonn E, Zhu J, et al. First stroke reduced 44% by well-tolerated medications. Stroke outcomes from the heart outcomes prevention evaluation 3 study. Stroke 2018;49:A104.

Seventy-five percent of strokes are first strokes, and primary prevention by reducing risk factors is crucial for reducing the global burden of stroke. Bosch et al investigated the effectiveness of fixed-dose antihypertensive therapy and statin therapy for primary stroke prevention. They randomized 12,705 participants from 21 countries who demonstrated an intermediate risk of cardiovascular disease in a 2 × 2 factorial design to a fixed-dose candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily vs. placebo, and to rosuvastatin 10 mg daily or placebo. The mean age of the patients was 66 years, 46% were women, and 166 strokes occurred during a median follow-up of 5.6 years. Mean baseline blood pressure was 138/82 mmHg and the blood pressure difference between the treatment groups during follow-up averaged 6.0/3.0 mmHg. During the follow-up period, stroke was reduced by 20% (95% confidence interval [CI], 0.59-1.08; P = 0.14) with candesartan/hydrochlorothiazide and 30% (95% CI, 0.5-20.95) with rosuvastatin. In a subgroup analysis, participants in the upper third of systolic blood pressure (> 143.5 mmHg) had stroke reduced by 42% (95% CI, 0.37-0.90; P < 0.02). Rosuvastatin reduced all stroke by 30%, but considering hemorrhagic strokes, 15 occurred among those assigned rosuvastatin vs. 12 with rosuvastatin placebo. Those assigned to both rosuvastatin and candesartan/hydrochlorothiazide had stroke reduced by 44% (95% CI, 0.36-0.87; P = 0.009). There was no difference in the rates of medication discontinuation between the groups that took active drugs compared to placebo-assigned patients. In this real-world study, fixed-dose candesartan/hydrochlorothiazide combined with low-dose rosuvastatin reduced first stroke by 44% in patients at intermediate risk of cardiovascular disease and was well tolerated, with minimum dropout of patients. This approach should be considered more widely in our efforts to reduce the global burden of stroke.