Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial
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DOI：
10.1016/s0140-6736(05)67528-9
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发表时间：
2005-10-08
期刊：
影响因子：
168.9
通讯作者：
Taton, J
中科院分区：
文献类型：
--
作者：
Dormandy, JA;Charbonnel, B;Taton, J
背景2型糖尿病患者是致命性和非致命性心肌梗死和卒中的高危人群。有间接证据表明，过氧化物酶体增殖物激活受体γ（PPAR γ）激动剂可以减少大血管并发症。因此，我们的目的是确定吡格列酮是否能降低2型糖尿病高危患者大血管病变的发病率和死亡率。方法我们在5238例有大血管病变证据的2型糖尿病患者中进行了一项前瞻性、随机对照试验。我们从基层医疗机构和医院招募病人。我们将患者分为口服吡格列酮组（n=2605）和安慰剂组（n =2633），吡格列酮剂量从15 mg调整至45 mg，与降糖药物和其他药物联合使用。我们的主要终点是全因死亡率、非致死性心肌梗死（包括无症状性心肌梗死）、卒中、急性冠状动脉综合征、冠状动脉或腿部动脉的血管内或外科干预以及踝关节以上截肢的复合终点。本研究注册为国际标准随机对照试验，编号ISRCTN NCT 00174993.Findings-2例患者失访，但被纳入分析。平均观察时间为34.5个月。吡格列酮组514/2605例患者和安慰剂组572/2633例患者至少发生1起主要复合终点事件（HR 0.90，95% CI 0.80-1.02，p=0.095）。主要次要终点是全因死亡率、非致死性心肌梗死和卒中的复合终点。吡格列酮组301例患者和安慰剂组358例患者达到该终点（0.84，0.72-0.98，p=0.027）。总体安全性和耐受性良好，吡格列酮的安全性特征未发生变化。占6%（2065年的149个）和4%吡格列酮组和安慰剂组分别有108例（2633例中的108例）因心力衰竭入院;心力衰竭的死亡率在各组之间没有差异。解释吡格列酮降低了全因死亡率，非致死性心肌梗死，和大血管事件高风险的2型糖尿病患者中的中风。
Background Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.Methods We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993.Findings Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups.Interpretation Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events.