Singh Sonal, Loke Yoon K, Furberg Curt D
Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
JAMA. 2007 Sep 12;298(10):1189-95. doi: 10.1001/jama.298.10.1189.
Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes.
To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality.
We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007.
Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events.
Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years).
Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I(2) = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality).
Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.
近期有关使用罗格列酮出现严重不良事件的报道引发了关于其危害证据是否足以证明可用于治疗2型糖尿病的质疑。
系统评价罗格列酮的长期心血管风险，包括心肌梗死、心力衰竭和心血管疾病死亡率。
我们检索了MEDLINE、葛兰素史克临床试验注册库、美国食品药品监督管理局网站以及截至2007年5月以英文发表的随机对照试验、系统评价和荟萃分析的产品说明书。
入选的研究需为罗格列酮预防或治疗2型糖尿病的随机对照试验，随访时间至少12个月，监测心血管不良事件并提供所有不良事件的数值数据。在对140项心血管事件试验进行详细筛选后，纳入了4项研究。
采用固定效应荟萃分析方法估计4项随机对照试验（n = 14291，其中6421例接受罗格列酮治疗，7870例接受对照治疗，随访时间为1 - 4年）中心肌梗死、心力衰竭和心血管疾病死亡率的相对风险（RRs）。
罗格列酮显著增加心肌梗死风险（94/6421例 vs 83/7870例；RR，1.42；95%置信区间[CI]，1.06 - 1.91；P = 0.02）和心力衰竭风险（102/6421例 vs 62/7870例；RR，2.09；95% CI，1.52 - 2.88；P < 0.001），而心血管疾病死亡率风险未显著增加（59/6421例 vs 72/7870例；RR，0.90；95% CI，0.63 - 1.26；P = 0.53）。这些终点指标在各试验中无明显异质性证据（心肌梗死I(2) = 0%，心力衰竭为18%；心血管疾病死亡率为0%）。
在糖耐量受损或2型糖尿病患者中，使用罗格列酮至少12个月会显著增加心肌梗死和心力衰竭风险，而心血管疾病死亡率风险未显著增加。
