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【drug-news】糖尿病药物安全仍然让人忧虑
The Questions Continue About Thiazolidinediones’ Safety
A new meta-analysis shows an elevated risk for congestive HF but no increase in cardiovascular death rate with either rosiglitazone or pioglitazone
Thiazolidinediones (TZDs) not only improve glycemic control as measured by lowered HbA1C levels but also have an independently positive cardiometabolic profile. However, none of the trials that established these benefits was designed or powered to detect TZDs’ effects on MI, congestive heart failure, or cardiovascular death rates. In May 2007, a meta-analysis of results from 42 trials (including unpublished as well as published data) uncovered evidence of adverse cardiovascular outcomes with rosiglitazone (Journal Watch Cardiology May 21 2007). A recently published interim analysis of an ongoing phase III trial of rosiglitazone (Journal Watch Cardiology Jun 6 2007) showed low and comparable rates of MI and death, but double the HF incidence seen with other diabetes drugs.
In a new meta-analysis of seven published, randomized, controlled trials that compared TZDs with standard oral antidiabetic drugs or placebo, investigators pooled risk estimates of cardiovascular outcomes in 20,191 patients randomized to either rosiglitazone (14,491) or pioglitazone (5700) who had either prediabetes or type 2 diabetes. Most patients did not have congestive HF or evidence of LV dysfunction at study entry. Trial durations were short (between 12 and 48 months).
Significantly more TZD recipients than controls developed congestive HF (2% vs. 1.4%), and increased HF risk was independent of a wide range of cardiac risk factors. An absence of heterogeneity across studies indicated a class effect. The risk for cardiovascular death was not greater in TZD recipients than in controls.
Comment: These findings suggest that the increased rate of congestive heart failure seen across these studies (1) seems to be a class effect of thiazolidinediones (although considerably less data on pioglitazone than on rosiglitazone were included in the analysis), and (2) was not associated with an increased risk for cardiovascular death. Whether, as the authors suggest, TZD-related fluid retention is a more benign cause of congestive HF than other causes is a questionable hypothesis that cannot be addressed by such short-term trials. This study is also limited by the exclusion of the many unpublished trials that were reported in the earlier meta-analysis, and it confirms once more that trialists continue to err in relying on surrogate instead of patient-important outcomes. As editorialists in three accompanying pieces comment, TZDs’ role in current and future medical practice is doubtful at best.
— Beat J. Meyer, MD
Published in Journal Watch Cardiology September 28, 2007 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。
糖尿病药物安全仍然让人忧虑
The Questions Continue About Thiazolidinediones’ Safety
继续跟踪噻唑烷二酮类药物的安全问题
A new meta-analysis shows an elevated risk for congestive HF but no increase in cardiovascular death rate with either rosiglitazone or pioglitazone
最新meta分析结果显示罗格列酮和匹格列酮增加充血性心力衰竭的发生率，但是并不增加心血管事件的死亡率。
Thiazolidinediones (TZDs) not only improve glycemic control as measured by lowered HbA1C levels but also have an independently positive cardiometabolic profile. However, none of the trials that established these benefits was designed or powered to detect TZDs’ effects on MI, congestive heart failure, or cardiovascular death rates. In May 2007, a meta-analysis of results from 42 trials (including unpublished as well as published data) uncovered evidence of adverse cardiovascular outcomes with rosiglitazone (Journal Watch Cardiology May 21 2007). A recently published interim analysis of an ongoing phase III trial of rosiglitazone (Journal Watch Cardiology Jun 6 2007) showed low and comparable rates of MI and death, but double the HF incidence seen with other diabetes drugs.
噻唑烷二酮类药物（TZDs）不仅通过检测降低了的血红蛋白A1C（HbA1C）水平，提高对升糖指数控制，并且对心血管代谢方面也有独立的正向效应。然而，没有一项临床试验在检测其（对糖尿病）好处的同时，设计去检测TZDs对心肌梗死、充血性心力衰竭和心血管事件死亡率的影响。2007年5月，来自于42项试验（包括出版和没有出版的数据）的meta分析揭示了罗格列酮对心血管不良反应的证据（Journal Watch Cardiology May 21 2007）。最近出版的正在进行的罗格列酮III期临床试验的中间分析（Journal Watch Cardiology Jun 6 2007）指出，与其他治疗糖尿病相比，罗格列酮有低的或者相当的MI发生率和死亡率，但是其心衰的发生率是其它药物的2倍。
In a new meta-analysis of seven published, randomized, controlled trials that compared TZDs with standard oral antidiabetic drugs or placebo, investigators pooled risk estimates of cardiovascular outcomes in 20,191 patients randomized to either rosiglitazone (14,491) or pioglitazone (5700) who had either prediabetes or type 2 diabetes. Most patients did not have congestive HF or evidence of LV dysfunction at study entry. Trial durations were short (between 12 and 48 months).
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作者:admin@医学,生命科学 2011-07-21 07:26
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