Abstract

Aims: As hazard ratios are difficult to interpret, we pooled data from eight contemporary cardiovascular outcomes trials (CVOT) of GLP1-RA drugs using restricted mean survival time (RMST) to evaluate their cardio-protective effect. Material and methods: Data from eight multinational CVOT RCT's of GLP1-RA drugs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan Meier plots. The differences between arms in restricted mean survival time (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST were pooled using an inverse variance weighted random effects model; heterogeneity was tested with the Cochran's Q statistic. The endpoints studied were: 3-point major adverse cardiovascular event (3-pt MACE), all-cause mortality, stroke, cardiovascular mortality, and myocardial infarction. Results: We included eight large (3183-14 752 participants, total = 60 080; median follow-up range: 1.5 – 5.4 years) GLP1-RA trials. Among GLP1-RA recipients, we observed an average delay in 3-point MACE by 0.03, 0.15, 0.37 and 0.63 months at 12, 24, 36, 48 months respectively. At 48 months, while CV mortality was comparable in both arms [pooled ΔRMST 0.163 (-0.112, 0.437); p = 0.24], overall survival was higher [ΔRMST = 0.261 (0.08 – 0.43) months] and stroke was delayed [ΔRMST 0.22 (0.15 – 0.33)] in patients receiving GLP1-RA. Conclusions: GLP1-RA may delay the occurrence of MACE by an average 0.6 months at 48 months with meaningfully larger gains in patients with cardiovascular disease. This metric maybe easier for clinicians and patients to interpret than hazard ratios which assume a knowledge of absolute risk in the absence of treatment.