Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)
Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)
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DOI：
10.1161/circulationaha.117.029095
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发表时间：
2017-12-19
期刊：
影响因子：
37.8
通讯作者：
Braunwald, Eugene
中科院分区：
文献类型：
--
作者：
Bohula, Erin A.;Wiviott, Stephen D.;Braunwald, Eugene
背景：经历急性冠状动脉综合征的患者复发缺血事件（包括中风）的风险更高。在急性冠状动脉综合征后病情稳定的患者中，将依折麦布添加到他汀类药物治疗中可改善心血管结局。我们调查了疗效的依折麦布辛伐他汀预防中风和其他不良心血管事件的IMPROVE-IT（改善减少的结果：Vytorin疗效国际试验），重点对患者中风前randomization.METHODS：患者经历了急性冠脉综合征随机安慰剂/辛伐他汀或依折麦布/辛伐他汀方案，并随访了中位数为6年。治疗效果进行了评估，为整个人口和亚组的第一次和总（第一次和随后）事件的终点中风的任何病因，中风亚型，并在7 years.RESULTS的主要试验终点：18 144例患者中，641（3.5%）经历了至少1次中风，大多数是缺血性（527，82%）。卒中的独立预测因素包括既往卒中、高龄、房颤、充血性心力衰竭、糖尿病、心肌梗死和肾功能不全。任何病因的首次卒中事件无显著减少依折麦布/辛伐他汀vs安慰剂/辛伐他汀（4.2% vs 4.8%;风险比[HR]，0.86; 95%置信区间[CI]，0.73-1.00; P=0.052），缺血性卒中显著降低21%（3.4% vs 4.1%; HR，0.79; 95% CI，0.67-0.94; P=0.008）和出血性卒中无显著增加（0.8% vs 0.6%; HR，1.38; 95% CI，0.93-2.04; P=0.11）。评价总事件，包括首次和所有复发性卒中，依折麦布/辛伐他汀可降低任何病因的卒中（HR，0. 83; 95% CI，0. 70 - 0. 98; P= 0. 029）和缺血性卒中（HR，0. 76; 95% CI，0. 63 - 0. 91; P= 0. 003）。在随机化前发生过卒中的患者复发风险较高，任何病因卒中的绝对风险降低8.6（10.2% vs 18.8%;需要治疗的人数=12; HR，0.60; 95% CI，0.38-0.95; P=0.030）和缺血性卒中7.6%（8.7% vs 16.3%;需要治疗的人数=13; HR，0.52; 95% CI，0.31-0.86; P=0.011）。急性冠脉综合征后病情稳定的患者在辛伐他汀基础上加用依折麦布可降低缺血性卒中的发生率，在先前中风的患者中观察到特别大的影响。
BACKGROUND: Patients who experience an acute coronary syndrome are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after acute coronary syndrome. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), with a focus on patients with a stroke before randomization.METHODS: Patients who experienced acute coronary syndrome were randomized to a placebo/simvastatin or ezetimibe/simvastatin regimen and followed for a median of 6 years. Treatment efficacy was assessed for the entire population and by subgroups for the first and total (first and subsequent) events for the end points of stroke of any etiology, stroke subtypes, and the primary trial end point at 7 years.RESULTS: Of 18 144 patients, 641 (3.5%) experienced at least 1 stroke; most were ischemic (527, 82%). Independent predictors of stroke included prior stroke, older age, atrial fibrillation, congestive heart failure, diabetes mellitus, myocardial infarction, and renal dysfunction. There was a nonsignificant reduction in the first event of stroke of any etiology (4.2% versus 4.8%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.73-1.00; P=0.052) with ezetimibe/simvastatin versus placebo/simvastatin, driven by a significant 21% reduction in ischemic stroke (3.4% versus 4.1%; HR, 0.79; 95% CI, 0.67-0.94; P=0.008) and a nonsignificant increase in hemorrhagic stroke (0.8% versus 0.6%; HR, 1.38; 95% CI, 0.93-2.04; P=0.11). Evaluating total events, including the first and all recurrent strokes, ezetimibe/ simvastatin reduced stroke of any etiology (HR, 0.83; 95% CI, 0.70-0.98; P=0.029) and ischemic stroke (HR, 0.76; 95% CI, 0.63-0.91; P=0.003). Patients who had experienced a stroke prior to randomization were at a higher risk of recurrence and demonstrated an absolute risk reduction of 8.6% for stroke of any etiology (10.2% versus 18.8%; number needed to treat=12; HR, 0.60; 95% CI, 0.38-0.95; P=0.030) and 7.6% for ischemic stroke (8.7% versus 16.3%; number needed to treat=13; HR, 0.52; 95% CI, 0.31-0.86; P=0.011) with ezetimibe added to simvastatin therapy.CONCLUSIONS: The addition of ezetimibe to simvastatin in patients stabilized after acute coronary syndrome reduces the frequency of ischemic stroke, with a particularly large effect seen in patients with a prior stroke.