Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.
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DOI：
10.1056/nejmoa1506930
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发表时间：
2016-04-07
期刊：
影响因子：
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通讯作者：
IRIS Trial Investigators
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作者：
Kernan WN;Viscoli CM;Furie KL;Young LH;Inzucchi SE;Gorman M;Guarino PD;Lovejoy AM;Peduzzi PN;Conwit R;Brass LM;Schwartz GG;Adams HP Jr;Berger L;Carolei A;Clark W;Coull B;Ford GA;Kleindorfer D;O'Leary JR;Parsons MW;Ringleb P;Sen S;Spence JD;Tanne D;Wang D;Winder TR;IRIS Trial Investigators
缺血性卒中或短暂性脑缺血发作（TIA）患者尽管目前有预防性治疗，但未来发生心血管事件的风险仍会增加。胰岛素抵抗是中风和心肌梗死的危险因素，这一发现提高了吡格列酮改善胰岛素敏感性的可能性，使脑血管疾病患者受益。在这项多中心、双盲试验中，我们将3876例近期有缺血性卒中或TIA的患者随机分配接受吡格列酮（目标剂量，每日45 mg）或安慰剂治疗。符合条件的患者没有糖尿病，但根据胰岛素抵抗的稳态模型评估（HOMA-IR）指数评分超过3.0，发现有胰岛素抵抗。主要结局为致死性或非致死性卒中或心肌梗死。4.8年时，吡格列酮组1939例患者中有175例（9.0%）发生主要结局，安慰剂组1937例患者中有228例（11.8%）发生主要结局（吡格列酮组风险比为0.76; 95%置信区间[CI]为0.62 - 0.93; P = 0.007）。分别有73名患者（3.8%）和149名患者（7.7%）发生糖尿病（风险比，0.48; 95%CI，0.33 - 0.69; P <0.001）。全因死亡率无显著组间差异（风险比，0.93; 95%CI，0.73 - 1.17; P = 0.52）。吡格列酮组体重增加超过4.5 kg的发生率高于安慰剂组（52.2% vs. 33.7%，P <0.001）、水肿（35.6% vs. 24.9%，P <0.001）和需要手术或住院治疗的骨折（5.1% vs. 3.2%，P = 0.003）。在这项试验中，有胰岛素抵抗沿着近期缺血性卒中或TIA病史的非糖尿病患者中，接受吡格列酮的患者发生卒中或心肌梗死的风险低于接受安慰剂的患者。吡格列酮还与糖尿病风险降低相关，但与体重增加、水肿和骨折风险升高相关。（由国家神经疾病和中风研究所资助; www.example.com编号，NCT 00091949。
Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003). In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)