Lincoff A Michael, Wolski Kathy, Nicholls Stephen J, Nissen Steven E
Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
JAMA. 2007 Sep 12;298(10):1180-8. doi: 10.1001/jama.298.10.1180.
Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on cardiovascular outcomes.
To systematically evaluate the effect of pioglitazone on ischemic cardiovascular events.
A database containing individual patient-level time-to-event data collected during pioglitazone clinical trials was transferred from the drug's manufacturer for independent analysis. Trials were included if they were randomized, double-blinded, and controlled with placebo or active comparator.
The primary outcome was a composite of death, myocardial infarction, or stroke. Secondary outcome measures included the incidence of serious heart failure. A fixed-effects approach was used to combine the estimates across the duration strata and statistical heterogeneity across all the trials was tested with the I2 statistic.
A total of 19 trials enrolling 16 390 patients were analyzed. Study drug treatment duration ranged from 4 months to 3.5 years. Death, myocardial infarction, or stroke occurred in 375 of 8554 patients (4.4%) receiving pioglitazone and 450 of 7836 patients (5.7%) receiving control therapy (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72-0.94; P = .005). Progressive separation of time-to-event curves became apparent after approximately 1 year of therapy. Individual components of the primary end point were all reduced by a similar magnitude with pioglitazone treatment, with HRs ranging from 0.80 to 0.92. Serious heart failure was reported in 200 (2.3%) of the pioglitazone-treated patients and 139 (1.8%) of the control patients (HR, 1.41; 95% CI, 1.14-1.76; P = .002). The magnitude and direction of the favorable effect of pioglitazone on ischemic events and unfavorable effect on heart failure was homogeneous across trials of different durations, for different comparators, and for patients with or without established vascular disease. There was no evidence of heterogeneity across the trials for either end point (I2 = 0%; P = .87 for the composite end point and I2 = 0%; P = .97 for heart failure).
Pioglitazone is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality.
吡格列酮广泛用于2型糖尿病患者的血糖控制，但这类药物对心血管结局的影响证据不一。
系统评价吡格列酮对缺血性心血管事件的影响。
从药物制造商处转来一个包含吡格列酮临床试验期间收集的个体患者水平事件发生时间数据的数据库，用于独立分析。纳入的试验需为随机、双盲且采用安慰剂或活性对照的试验。
主要结局为死亡、心肌梗死或卒中的复合结局。次要结局指标包括严重心力衰竭的发生率。采用固定效应方法合并各时间段分层的估计值，并使用I²统计量检验所有试验的统计异质性。
共分析了19项纳入16390例患者的试验。研究药物治疗时间为4个月至3.5年。接受吡格列酮治疗的8554例患者中有375例（4.4%）发生死亡、心肌梗死或卒中，接受对照治疗的7836例患者中有450例（5.7%）发生上述情况（风险比[HR]，0.82；95%置信区间[CI]，0.72 - 0.94；P = 0.005）。治疗约1年后，事件发生时间曲线开始明显分离。吡格列酮治疗使主要终点的各个组成部分均有相似程度的降低，HR范围为0.80至0.92。吡格列酮治疗组有200例（2.3%）患者报告发生严重心力衰竭，对照组有139例（1.8%）患者发生（HR，1.41；95% CI，1.14 - 1.76；P = 0.002）。在不同持续时间、不同对照以及有无已确诊血管疾病的患者的试验中，吡格列酮对缺血性事件的有利影响程度和方向以及对心力衰竭的不利影响均具有同质性。两个终点在各试验中均无异质性证据（I² = 0%；复合终点P = 0.87，心力衰竭P = 0.97）。
在不同类型的糖尿病患者中，吡格列酮与死亡、心肌梗死或卒中风险显著降低相关。吡格列酮会增加严重心力衰竭的发生风险，尽管未伴随死亡率增加。
