Estimating the True MACE Benefits From Tirzepatide in SURPASS-CVOT Using an Imputed Placebo Analysis of REWIND.

research_design_and_methods

The indirect comparison with placebo was conducted for primary (MACE-3) and secondary outcomes of SURPASS-CVOT.

对SURPASS-CVOT的主要（MACE-3）和次要结果进行了与安慰剂的间接比较。

The analysis included data from REWIND participants who would have been eligible for SURPASS-CVOT and all participants from SURPASS-CVOT.

分析包括了符合SURPASS-CVOT资格的REWIND参与者的数据以及SURPASS-CVOT的所有参与者。

Propensity score estimation was used to adjust for differences in participant characteristics between studies.

使用倾向得分估计来调整研究之间参与者特征的差异。

The indirect analysis of the treatment effect was derived by multiplying the hazard ratio(HR) for MACE-3 between tirzepatide and dulaglutide in SURPASS-CVOT by the HR for dulaglutide versus placebo in REWIND.

通过将SURPASS-CVOT中tirzepatide与dulaglutide对MACE-3的危险比(HR)与REWIND中dulaglutide与安慰剂的HR相乘，得出了治疗效果的间接分析。

Sensitivity analyses were performed using unadjusted analyses, including both the selected REWIND and the entire REWIND populations, and adjusted analysis in the entire REWIND population.

使用未调整的分析进行了敏感性分析，包括选定的REWIND人群和整个REWIND人群，以及在整个REWIND人群中进行的调整分析。

Post hoc sensitivity analyses used data from a recent glucagon-like peptide 1 receptor agonist (GLP-1RA) meta-analysisthat included REWIND.

事后敏感性分析使用了最近一次包括REWIND在内的胰高血糖素样肽-1受体激动剂(GLP-1RA)荟萃分析的数据。

Results

Analyses included 2,055 of 9,901 participants from REWIND and all 13,165 participants from SURPASS-CVOT.

分析包括了REWIND的2,055名参与者中的9,901名和SURPASS-CVOT的所有13,165名参与者。

In indirect treatment effect comparisons, tirzepatide versus placebo was associated with lower MACE-3 (HR 0.72; 95% CI 0.55, 0.94), death from CV cause or heart failure events (HR 0.70; 95% CI 0.51, 0.96), and all-cause death (HR 0.61; 95% CI 0.45, 0.82).

在间接治疗效果比较中，tirzepatide与安慰剂相比，与较低的主要心血管不良事件（MACE-3）（HR 0.72; 95% CI 0.55, 0.94）、心血管原因死亡或心力衰竭事件（HR 0.70; 95% CI 0.51, 0.96）以及全因死亡（HR 0.61; 95% CI 0.45, 0.82）相关。

Sensitivity analyses, including nonadjusted or the entire REWIND cohort data or meta-analysisdata for GLP-1RAs, were generally consistent.

敏感性分析，包括未调整的或整个REWIND队列数据或GLP-1RAs的荟萃分析数据，总体上是一致的。

Conclusions

In this indirect prespecified exploratory comparison, tirzepatide compared with imputed placebo was associated with reduced CV outcomes and all-cause mortality in participants with type 2 diabetes and established atherosclerotic CV disease.

在这项预先设定的间接探索性比较中，tirzepatide与估算的安慰剂相比，在2型糖尿病患者和已建立的动脉粥样硬化性心血管疾病患者中，与降低心血管结果和全因死亡率相关。