Abstract 104: First Stroke Reduced 44 Percent by Well Tolerated Medications. Stroke Outcomes From the Heart Outcomes Prevention Evaluation 3 Study

Background: Most (75%) strokes are first strokes, and primary prevention is crucial for reducing the global burden of stroke The role of fixed-dose antihypertensive therapy and statin drugs for primary stroke prevention has not been adequately defined. Methods: Using a 2x2 factorial design, 12,705 participants from 21 countries with an intermediate risk of cardiovascular disease but without overt vascular disease were randomized to fixed-dose candesartan 16 mg plus hydrochlorothiazide (HCTZ) 12.5 mg daily or placebo and to rosuvastatin 10mg daily or placebo. Results: Mean age was 66 years, 46% were women, and 166 strokes occurred during a median follow-up of 5.6 years. Mean baseline blood pressure (BP) was 138/82 mmHg and the BP difference between the treatment groups during follow-up averaged 6.0/3.0 mmHg. Stroke was reduced by 20% (confidence interval [CI], 0.59-1.08; p =0.14) by candesartan/HCTZ and 30% (CI, 0.52-0.95) by rosuvastatin. In a pre-specified subgroup analysis, participants in the upper third of systolic BP (>143.5 mmHg) had stroke reduced by 42% (CI, 0.37-0.90, p =0.02). Rosuvatatin reduced all stroke by 30% (CI, 0.52-0.95; p =0.02); but considering hemorrhagic strokes: 15 among those assigned rosuvastatin vs. 12 with rosuvastatin-placebo. Those assigned both rosuvatatin and candesartan/HCTZ had stroke reduced by 44% ( CI, 0.36-0.87; p =0.009). Rates of permanent discontinuation did not differ significantly between active and placebo-assigned patients. Conclusions: Fixed-dose candesartan/HCTZ combined with low-dose rosuvastatin reduced first stroke by 44% in patients at intermediate risk of cardiovascular disease and was well-tolerated. Among those with systolic BP >143.5 mmHg, fixed-dose candesartan/HCTZ reduces first stroke by 42%,