Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).
School of Rehabilitation Science (J.B.), McMaster University, Hamilton, ON, Canada.
Stroke. 2021 Aug;52(8):2494-2501. doi: 10.1161/STROKEAHA.120.030790. Epub 2021 May 14.
The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.
Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.
Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).
Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.
HOPE-3 试验（心脏结局预防评估-3）发现，降压治疗联合他汀类药物可降低心血管风险中等的人群首次发生中风的风险。我们报告了中风亚型、预测因素、关键亚组治疗效果的二次分析结果。
在 21 个国家，有血管危险因素但无明显心血管疾病的 12705 名参与者，被随机分配至坎地沙坦 16mg 加氢氯噻嗪 12.5mg 每日一次或安慰剂组，以及瑞舒伐他汀 10mg 每日一次或安慰剂组。评估了干预措施对中风亚型的影响。
参与者年龄为 66 岁，46%为女性。基线血压（138/82mmHg）降低 6.0/3.0mmHg，低密度脂蛋白胆固醇（LDL-C；3.3mmol/L）降低 0.90mmol/L。在 5.6 年的随访期间，有 169 例中风发生（117 例缺血性中风，29 例出血性中风，23 例未确定病因的中风）。降压治疗并未显著降低中风风险（风险比[HR]，0.80[95%置信区间，0.59-1.08]）、缺血性中风（HR，0.80[95%置信区间，0.55-1.15]）、出血性中风（HR，0.71[95%置信区间，0.34-1.48]）或未确定病因的中风（HR，0.92[95%置信区间，0.41-2.08]）。瑞舒伐他汀可显著降低中风风险（HR，0.70[95%置信区间，0.52-0.95]），主要降低缺血性中风风险（HR，0.53[95%置信区间，0.37-0.78]），但对出血性中风（HR，1.22[95%置信区间，0.59-2.54]）或未确定病因的中风（HR，1.29[95%置信区间，0.57-2.95]）无显著影响。与双安慰剂相比，两药联合治疗可显著降低中风风险（HR，0.56[95%置信区间，0.36-0.87]）和缺血性中风风险（HR，0.41[95%置信区间，0.23-0.72]）。
在心血管风险中等但无明显心血管疾病的人群中，瑞舒伐他汀 10mg 每日可显著降低首次中风的发生。降压联合瑞舒伐他汀治疗可降低 59%的缺血性中风风险。两种疗法均安全且通常耐受良好。
