西格列汀使用与 2 型糖尿病心力衰竭住院及相关结局的关系：一项随机临床试验的二次分析。

Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial.

机构信息

Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas.

Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

出版信息

JAMA Cardiol. 2016 May 1;1(2):126-35. doi: 10.1001/jamacardio.2016.0103.

DOI:10.1001/jamacardio.2016.0103

PMID:27437883

Abstract

IMPORTANCE

Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS).

OBJECTIVE

To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes.

DESIGN, SETTING, AND PARTICIPANTS: TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015.

INTERVENTIONS

Patients were randomized to sitagliptin vs placebo added to standard care.

MAIN OUTCOMES AND MEASURES

Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death.

RESULTS

Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16).

CONCLUSIONS AND RELEVANCE

Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00790205.

摘要

重要性

先前的试验结果表明，二肽基肽酶 4 抑制剂（DPP4i）的使用可能会增加 2 型糖尿病（T2DM）患者心力衰竭（HF）的风险。DPP4i 西格列汀在评估西格列汀心血管结局的试验（TECOS）中已被证明在主要和次要复合动脉粥样硬化心血管（CV）结局方面与安慰剂无差异。

目的

评估西格列汀的使用与 HF 住院（hHF）和相关结局的关系。

设计、地点和参与者：TECOS 是一项随机、双盲、安慰剂对照的研究，评估了西格列汀与安慰剂在 T2DM 和已发生动脉粥样硬化血管疾病患者中，与常规抗高血糖治疗和 CV 护理联合使用的 CV 安全性。中位随访时间为 2.9 年。该研究地点在 38 个国家的 673 个地点。参与者包括 14671 名 T2DM 和动脉粥样硬化血管疾病患者。研究日期为 2008 年 12 月至 2015 年 3 月。

干预措施

患者被随机分配至西格列汀或安慰剂加标准治疗。

主要结果和测量

预先指定的次要分析比较了 hHF、hHF 或 CV 死亡以及 hHF 或全因死亡复合结局的总体影响以及预先指定的亚组中的影响。支持性分析包括总 hHF 事件（首次和再次）和 hHF 后的死亡。荟萃分析评估了 DPP4i 对 hHF 和 hHF 或 CV 死亡的影响。

结果

在 14671 名患者中，7332 名患者被随机分配至西格列汀组，7339 名患者被随机分配至安慰剂组。HF 住院发生在西格列汀组（3.1%，228 例）和安慰剂组（3.1%，229 例），分别（未调整的危险比，1.00；95%CI，0.83-1.19）。西格列汀组（n=345）和安慰剂组（n=347）的总 hHF 事件也无差异（未调整的危险比，1.00；95%CI，0.80-1.25）。西格列汀组和安慰剂组 hHF 后的全因死亡率相似（分别为 29.8%和 28.8%），CV 死亡率也相似（分别为 22.4%和 23.1%）。在 21 个因素的亚组分析中，没有观察到西格列汀对 hHF 影响的异质性（所有交互作用的 P>0.10）。对来自 3 项报告的 DPP4i CV 结局试验的 hHF 结果进行的荟萃分析显示存在中度异质性（I2=44.9，P=0.16）。