吡格列酮对有或无既往卒中的2型糖尿病患者的影响：来自PROactive（前瞻性吡格列酮大血管事件临床试验04）的结果
Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04).
作者信息
Wilcox Robert, Bousser Marie-Germaine, Betteridge D John, Schernthaner Guntram, Pirags Valdis, Kupfer Stuart, Dormandy John
机构信息
Department of Cardiovascular Medicine, Queen's Medical Centre, University Hospital, Nottingham, UK.
出版信息
Stroke. 2007 Mar;38(3):865-73. doi: 10.1161/01.STR.0000257974.06317.49. Epub 2007 Feb 8.
BACKGROUND AND PURPOSE
Diabetes is an important risk factor for stroke. We conducted analyses in patients who had entered the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) with a history of stroke or without stroke.
METHODS
The prospective, double-blind PROactive (mean duration, 34.5 months) randomized 5238 patients with type 2 diabetes and a history of macrovascular disease to pioglitazone (titrated to 45 mg) or placebo, in addition to current diabetes and cardiovascular medications. Cardiovascular end-point events were independently adjudicated. This analysis evaluated the risk of stroke and other cardiovascular outcomes in patients with (n=984) and without (n=4254) prior stroke.
RESULTS
In patients with previous stroke (n=486 in the pioglitazone group and n=498 in the placebo group), there was a trend of benefit with pioglitazone for the primary end point of all-cause death, nonfatal myocardial infarction, acute coronary syndrome, and cardiac intervention (including coronary artery bypass graft or percutaneous coronary intervention), stroke, major leg amputation, or bypass surgery or leg revascularization (hazard ratio[HR]=0.78, event rate=20.2% pioglitazone vs 25.3% placebo; 95% CI=0.60-1.02; P=0.0670) and for the main secondary end point of all-cause death, nonfatal myocardial infarction, or nonfatal stroke (HR=0.78, event rate=15.6% pioglitazone vs 19.7% placebo; 95% CI=0.58-1.06; P=0.1095). Pioglitazone reduced fatal or nonfatal stroke (HR=0.53, event rate=5.6% pioglitazone vs 10.2% placebo; 95% CI=0.34-0.85; P=0.0085) and cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR=0.72, event rate=13.0% pioglitazone vs 17.7% placebo; 95% CI=0.52-1.00; P=0.0467). Higher event rates were observed in patients with prior stroke compared with those without prior stroke. In patients without prior stroke, no treatment effect was observed for a first stroke.
CONCLUSIONS
In a subgroup analysis from PROactive, pioglitazone reduced the risk of recurrent stroke significantly in high-risk patients with type 2 diabetes.
背景与目的
糖尿病是中风的重要危险因素。我们对既往有中风病史或无中风病史且已进入大血管事件前瞻性吡格列酮临床试验（PROactive）的患者进行了分析。
方法
前瞻性、双盲的PROactive试验（平均持续时间34.5个月）将5238例患有2型糖尿病且有大血管疾病病史的患者随机分为吡格列酮组（滴定至45毫克）或安慰剂组，同时继续使用当前的糖尿病和心血管药物。心血管终点事件由独立判定。本分析评估了既往有中风（n = 984）和无中风（n = 4254）患者的中风及其他心血管结局风险。
结果
在既往有中风的患者中（吡格列酮组486例，安慰剂组498例），吡格列酮在全因死亡、非致命性心肌梗死、急性冠状动脉综合征、心脏介入治疗（包括冠状动脉搭桥术或经皮冠状动脉介入治疗）、中风、大腿大截肢、或搭桥手术或腿部血管重建等主要终点方面有获益趋势（风险比[HR]=0.78，吡格列酮组事件发生率为20.2%，安慰剂组为25.3%；95%置信区间=0.60 - 1.02；P = 0.0670），在全因死亡、非致命性心肌梗死或非致命性中风等主要次要终点方面也有获益趋势（HR = 0.78，吡格列酮组事件发生率为15.6%，安慰剂组为19.7%；95%置信区间=0.58 - 1.06；P = 0.1095）。吡格列酮降低了致命或非致命性中风（HR = 0.53，吡格列酮组事件发生率为5.6%，安慰剂组为10.2%；95%置信区间=0.34 - 0.85；P = 0.0085）以及心血管死亡、非致命性心肌梗死或非致命性中风的风险（HR = 0.72，吡格列酮组事件发生率为13.0%，安慰剂组为17.7%；95%置信区间=0.52 - 1.00；P = 0.0467）。与无既往中风的患者相比，既往有中风的患者事件发生率更高。在无既往中风的患者中，未观察到对首次中风的治疗效果。
结论
在PROactive试验的亚组分析中，吡格列酮显著降低了2型糖尿病高危患者复发性中风的风险。
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