Division of Diabetology, Medical Department I, St. Josef-Hospital (Ruhr-University), Bochum, Germany.
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cardiovasc Diabetol. 2019 Sep 3;18(1):116. doi: 10.1186/s12933-019-0921-2.
To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).
TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses.
During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes.
In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205.
在评估西格列汀心血管结局的试验（TECOS）中，观察 DPP-4i 西格列汀对 MI 期间和之后心血管结局的影响。
TECOS 将 14671 名患有 2 型糖尿病和动脉粥样硬化性心血管疾病（ASCVD）的患者随机分为西格列汀组或安慰剂组，同时接受常规治疗。对于那些在试验期间发生心肌梗死（MI）的患者，我们分析了病死率；对于那些发生非致死性 MI 的患者，我们通过治疗组，使用 Cox 比例风险模型进行分析（左截断值为首次试验内 MI 时间），在未调整和调整潜在混杂因素的情况下，评估心血管（CV）复合结局（CV 死亡或心力衰竭住院[hHF]）。
在 TECOS 期间，616 名患者发生≥1 次 MI（西格列汀组 300 例，安慰剂组 316 例，HR 0.95，95%CI 0.81-1.11，P=0.49），其中 25 例死亡（分别为 11 例和 14 例））。591 名非致死性 MI 患者中，随后有 87 例（15%）死亡，其中 66 例（11%）为 CV 死亡，57 例（10%）发生 hHF。复合结局发生在 58 名（20.1%；每 100 人年 13.9 例）西格列汀组患者和 50 名（16.6%；每 100 人年 11.7 例）安慰剂组患者中（HR 1.21，95%CI 0.83-1.77，P=0.32，调整后的 HR 1.23，95%CI 0.83-1.82，P=0.31）。事后分析也显示，两组间 MI 后结局无显著差异。
在发生 MI 的 2 型糖尿病和 ASCVD 患者中，西格列汀并未降低随后发生 CV 死亡或 hHF 的风险，这与基于临床前动物模型的预期相反。临床试验注册临床Trials.gov 编号 NCT00790205。
