Alpert Medical School of Brown University, Providence, RI (S.Y., K.L.F.).
Yale School of Medicine, New Haven, CT (C.M.V., J.D., L.H.Y., S.E.I., A.M.L., W.N.K.).
Circulation. 2018 Jan 30;137(5):455-463. doi: 10.1161/CIRCULATIONAHA.117.030458. Epub 2017 Oct 30.
The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone reduced the risk for a composite outcome of stroke or myocardial infarction among nondiabetic patients with insulin resistance and a recent stroke or transient ischemic attack. The current planned secondary analysis uses updated 2013 consensus criteria for ischemic stroke to examine the effect of pioglitazone on stroke outcomes.
Participants were randomly assigned to receive pioglitazone (45 mg/d target dose) or placebo within 180 days of a qualifying ischemic stroke or transient ischemic attack and were followed for a maximum of 5 years. An independent committee, blinded to treatment assignments, adjudicated all potential stroke outcomes. Time to first stroke event was compared by treatment group, overall and by type of event (ischemic or hemorrhagic), using survival analyses and Cox proportional hazards models.
Among 3876 IRIS participants (mean age, 63 years; 65% male), 377 stroke events were observed in 319 participants over a median follow-up of 4.8 years. Pioglitazone was associated with a reduced risk for any stroke at 5 years (8.0% in comparison with 10.7% for the placebo group; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.94; log-rank =0.01). Pioglitazone reduced risk for ischemic strokes (HR, 0.72; 95% CI, 0.57-0.91; =0.005) but had no effect on risk for hemorrhagic events (HR, 1.00; 95% CI, 0.50-2.00; =1.00).
Pioglitazone was effective for secondary prevention of ischemic stroke in nondiabetic patients with insulin resistance.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00091949.
IRIS 试验（中风后胰岛素抵抗干预）表明，吡格列酮可降低胰岛素抵抗且近期发生中风或短暂性脑缺血发作的非糖尿病患者发生中风或心肌梗死复合结局的风险。目前计划进行的二次分析使用 2013 年缺血性中风共识标准来检查吡格列酮对中风结局的影响。
参与者在符合条件的缺血性中风或短暂性脑缺血发作后 180 天内被随机分配接受吡格列酮（目标剂量 45 mg/d）或安慰剂治疗，并随访最长 5 年。一个独立的委员会，对治疗分配不知情，对所有潜在的中风结局进行裁决。通过治疗组、总体和按事件类型（缺血性或出血性）进行生存分析和 Cox 比例风险模型比较首次中风事件的时间。
在 3876 名 IRIS 参与者（平均年龄 63 岁；65%为男性）中，319 名参与者中有 377 名在中位随访 4.8 年内发生了中风事件。吡格列酮可降低 5 年时任何中风的风险（与安慰剂组的 10.7%相比，吡格列酮组为 8.0%；风险比 [HR]，0.75；95%置信区间 [CI]，0.60-0.94；对数秩检验=0.01）。吡格列酮降低了缺血性中风的风险（HR，0.72；95%CI，0.57-0.91；=0.005），但对出血事件的风险没有影响（HR，1.00；95%CI，0.50-2.00；=1.00）。
吡格列酮可有效预防非糖尿病胰岛素抵抗患者的缺血性中风。
