First plus recurrent major adverse cardiovascular events with tirzepatide in patients with type 2 diabetes at high cardiovascular risk from SURPASS CVOT
D L Bhatt, A R Soares, H Nishiyama, J Kiljanski, I Pavo, D Dalessio, S J NichollsAbstract
Background/Introduction
In SURPASS-CVOT, tirzepatide (TZP) was non-inferior to dulaglutide (dula) in reducing the first occurrence of 3-component major adverse cardiovascular events (MACE-3) including myocardial infarction, stroke, or cardiovascular death, while superior in reducing MACE-5 (additionally including hospitalization for unstable angina and coronary revascularization) among patients with type 2 diabetes and established atherosclerotic cardiovascular disease. This pre-specified analysis assessed total (first and recurrent) cardiovascular events for MACE-5 and MACE-3.
Methods
SURPASS-CVOT was an active-comparator-controlled, double-blind, trial in which patients with type 2 diabetes and established atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly TZP up to 15 mg or dula 1.5 mg, an agent previously shown to reduce the incidence of cardiovascular events versus placebo. The rate ratio was estimated from the semi-parametric proportional rates model with treatment and SGLT-2i use at baseline as fixed effects.
Results
A total of 13,165 patients (29% female, mean age [SD]: 64.1 [8.8] yrs, BMI: 32.6kg/m2 [5.5], HbA1c: 8.4% [0.9]) were included in the modified intent to treat population (TZP 6586, dula 6579). CV history included coronary artery disease (65.0%), myocardial infarction (47.2%), stroke (19.2%), peripheral artery disease (25.3%), heart failure (20.3%), and coronary revascularization (57.2%). For MACE-5, TZP treatment was associated with a significantly lower total event burden, with 1,489 total events (1,112 first and 377 recurrent) compared with 1,696 total events in the dula group (1,240 first and 456 recurrent), rate ratio 0.87 (95% CI 0.80–0.95; p=0.002) Figure. For MACE-3, patients treated with TZP experienced fewer total events than those receiving dula, with 925 total events (801 first and 124 recurrent) versus 1,005 total events (862 first and 143 recurrent), respectively, rate ratio 0.91 (95% CI 0.82–1.01; p=0.070) Table. Fewer patients in the TZP group experienced multiple expanded MACE events compared with dula, with 835 patients experiencing a single event and 277 experiencing two or more events, versus 921 patients with a single event and 319 with two or more events in the dula group.
Conclusions
In patients with type 2 diabetes and established cardiovascular disease, TZP reduced the total burden of cardiovascular events compared with dula, with consistent benefits observed for first and recurrent MACE-5.