TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.)
TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
Circulation. 2017 Dec 19;136(25):2440-2450. doi: 10.1161/CIRCULATIONAHA.117.029095. Epub 2017 Sep 30.
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.
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.
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; =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; =0.008) and a nonsignificant increase in hemorrhagic stroke (0.8% versus 0.6%; HR, 1.38; 95% CI, 0.93-2.04; =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; =0.029) and ischemic stroke (HR, 0.76; 95% CI, 0.63-0.91; =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; =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; =0.011) with ezetimibe added to simvastatin therapy.
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.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.
经历急性冠状动脉综合征的患者发生复发性缺血事件（包括中风）的风险增加。依折麦布联合他汀类药物治疗稳定后的急性冠状动脉综合征患者，可改善心血管结局。我们研究了依折麦布联合辛伐他汀预防 IMPROVE-IT （改善结果：依泽替米贝他汀疗效国际试验）中风和其他不良心血管事件的疗效，重点关注随机分组前发生过中风的患者。
经历急性冠状动脉综合征的患者被随机分配到安慰剂/辛伐他汀或依折麦布/辛伐他汀治疗组，并随访中位数 6 年。评估了整个人群的治疗效果，并根据首次和（首次和随后的）事件对各亚组的终点（任何病因的中风、中风亚型和 7 年时的主要试验终点）进行评估。
在 18144 名患者中，641 名（3.5%）至少发生过 1 次中风；大多数为缺血性（527 名，82%）。中风的独立预测因素包括既往中风、年龄较大、心房颤动、充血性心力衰竭、糖尿病、心肌梗死和肾功能不全。依折麦布/辛伐他汀与安慰剂/辛伐他汀相比，首次任何病因中风的发生率略有降低（4.2%对 4.8%；危险比[HR]，0.86；95%置信区间[CI]，0.73-1.00；=0.052），主要是由于缺血性中风发生率显著降低 21%（3.4%对 4.1%；HR，0.79；95%CI，0.67-0.94；=0.008），出血性中风发生率略有增加（0.8%对 0.6%；HR，1.38；95%CI，0.93-2.04；=0.11）。评估包括首次和所有复发性中风在内的总事件，依折麦布/辛伐他汀降低了任何病因的中风（HR，0.83；95%CI，0.70-0.98；=0.029）和缺血性中风（HR，0.76；95%CI，0.63-0.91；=0.003）。随机分组前发生过中风的患者复发风险较高，依折麦布联合辛伐他汀治疗可使任何病因的中风绝对风险降低 8.6%（10.2%对 18.8%；需要治疗的人数[NNT]为 12；HR，0.60；95%CI，0.38-0.95；=0.030）和缺血性中风风险降低 7.6%（8.7%对 16.3%；NNT 为 13；HR，0.52；95%CI，0.31-0.86；=0.011）。
依折麦布联合辛伐他汀治疗稳定后的急性冠状动脉综合征患者可降低缺血性中风的发生率，尤其是在既往有中风的患者中效果更为显著。
