Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Am J Cardiovasc Drugs. 2011;11(2):115-28. doi: 10.2165/11587580-000000000-00000.
Recent meta-analyses of randomized clinical trials (RCTs) demonstrated a higher risk of heart failure (HF) with the use of thiazolidinediones (TZDs). However, this effect may have been diluted by including active controls. Also, it is uncertain whether the risk of HF is similar with rosiglitazone and pioglitazone.
This study quantified the risks of HF with the use of TZDs in patients with or at high risk of developing type 2 diabetes mellitus (DM), and evaluated differential effects by type of TZD. Secondarily, we evaluated risks of peripheral edema.
We performed a systematic review and meta-analysis of placebo-controlled RCTs evaluating the effect of rosiglitazone or pioglitazone on investigator-reported HF and edema. Articles published before 31 December 2009 were searched in MEDLINE, The Web of Science, and Scopus, and the data were extracted by three investigators. RCTs with ≥100 patients and ≥3 months of follow-up were included. We quantified the effect of TZDs as odds ratios (ORs) by using the Mantel-Haenzel and alternative models. We further evaluated the risk of serious/severe HF, and the effect of several trial characteristics on HF risk by subgroup analysis and meta-regression analysis.
29 trials (n = 20 254) were evaluated. TZDs were significantly associated with HF (TZD 360/6807 [5.3%] vs placebo 234/6328 [3.7%], OR 1.59; 95% CI 1.34, 1.89; p < 0.00001). The risk of HF was higher with rosiglitazone than with pioglitazone (2.73 [95% CI 1.46, 5.10] vs 1.51 [1.26, 1.81]; p = 0.06). TZDs were associated with a similar risk of serious/severe HF (OR 1.47; 95% CI 1.16, 1.87; p = 0.002). Use of TZDs was also associated with edema (OR 2.04; 95% CI 1.85, 2.26; p < 0.00001). HF and edema risks were consistent using Peto and random effects models. Risks of HF were significantly high for the subgroups of trials including patients with or at high risk for type 2 DM, and for the subgroup of trials with ≥12 months of follow-up. Meta-regression analysis showed that trials with lower overall baseline risk had higher HF risks.
In placebo-controlled trials of adult patients with or at high risk for type 2 DM, TZD therapy is significantly and consistently associated with a higher risk of HF. The risk of serious/severe HF is also increased with the use of TZDs. HF risks are similar to those of meta-analyses combining active- and placebo-controlled trials. The benefit/risk profile of TZDs should be considered when treating diabetic patients with or without prior HF.
最近的随机临床试验（RCT）荟萃分析显示，噻唑烷二酮（TZDs）的使用与心力衰竭（HF）风险增加相关。然而，这种效应可能因包括活性对照而被稀释。此外，罗格列酮和吡格列酮的 HF 风险是否相似尚不确定。
本研究定量评估了 TZDs 在有或高风险发生 2 型糖尿病（DM）的患者中的 HF 风险，并评估了 TZD 类型的差异效应。其次，我们评估了外周水肿的风险。
我们对评估罗格列酮或吡格列酮对研究者报告的 HF 和水肿影响的安慰剂对照 RCT 进行了系统评价和荟萃分析。在 MEDLINE、Web of Science 和 Scopus 中搜索了截至 2009 年 12 月 31 日之前发表的文章，由三位研究者提取数据。纳入了至少有 100 名患者且随访时间至少 3 个月的 RCT。我们使用 Mantel-Haenzel 和替代模型将 TZDs 的效果量化为比值比（OR）。我们进一步通过亚组分析和荟萃回归分析评估了严重/重度 HF 的风险以及几种试验特征对 HF 风险的影响。
评估了 29 项试验（n=20254）。TZDs 与 HF 显著相关（TZDs 360/6807 [5.3%] vs 安慰剂 234/6328 [3.7%]，OR 1.59；95%CI 1.34，1.89；p<0.00001）。与吡格列酮相比，罗格列酮的 HF 风险更高（2.73 [95%CI 1.46，5.10] vs 1.51 [1.26，1.81]；p=0.06）。TZDs 与严重/重度 HF 的风险相似（OR 1.47；95%CI 1.16，1.87；p=0.002）。TZDs 的使用也与水肿相关（OR 2.04；95%CI 1.85，2.26；p<0.00001）。Peto 和随机效应模型均显示 HF 和水肿风险一致。在包括有或高风险 2 型 DM 的患者的试验亚组中，以及在随访时间至少 12 个月的试验亚组中，HF 风险显著较高。荟萃回归分析显示，整体基线风险较低的试验 HF 风险较高。
在有或高风险发生 2 型 DM 的成年患者的安慰剂对照试验中，TZDs 治疗与 HF 风险显著增加相关。TZDs 的使用也会增加严重/重度 HF 的风险。HF 风险与结合活性对照和安慰剂对照试验的荟萃分析相似。在治疗有或无既往 HF 的糖尿病患者时，应考虑 TZDs 的获益/风险情况。
