This exploratory analysis compared tirzepatide up to 15 mg weekly with dulaglutide 1.5 mg weekly over four years. Patients had type 2 diabetes and atherosclerotic cardiovascular disease; 20.3% had a history of heart failure. For all-cause death or heart failure events, the hazard ratio was 0.83 (95%CI 0.70-0.99) with prior heart failure. It was 0.88 (95%CI 0.78-1.00) without. For the composite including coronary revascularisation, hazard ratios were 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00). The analysis was exploratory and subgroup-based, with overall non-inferiority already established.
Why it is interesting: Heart failure outcomes are compared between two incretin-based drugs in a head-to-head cardiovascular trial.
Abstract — the authors' own words, CC BY
Abstract
Aims
The impact of tirzepatide and dulaglutide on major adverse cardiovascular events (MACE) and heart failure (HF) outcomes according to HF status is unknown.
Methods and results
Patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease were treated with tirzepatide up to 15 mg or dulaglutide 1.5 mg weekly (average 4 years). The incidence of MACE-3 [cardiovascular (CV) death, myocardial infarction (MI), stroke], MACE-4 (CV death, MI, stroke, coronary revascularization) and composite of all-cause or CV death and hospitalization or urgent visits for HF were analysed in patients with and without a history of HF. A history of HF (20.3%) was associated with more coronary artery disease and prior MI. Incidences of event categories were higher in the HF group. The hazard ratio (HR) for all-cause death or hospitalization or urgent visits for HF on tirzepatide vs. dulaglutide was 0.83 [95% confidence interval (CI) 0.70–0.99] in patients with HF and 0.88 (95%CI 0.78–1.00) without HF. The HR for CV death or hospitalization or urgent visits for HF was 0.85 (95%CI 0.70–1.03) and 0.96 (95%CI 0.83–1.12), for MACE-3 0.90 (95%CI 0.76–1.08) and 0.93 (95%CI 0.83–1.04), and for MACE-4 0.81 (95%CI 0.69–0.95) and 0.91 (95%CI 0.83–1.00) in patients with and without HF, respectively. The patient-reported outcomes of APPADL and EQ-5D-5L visual analogue scores improved and were higher on tirzepatide in both groups.
Conclusion
With overall non-inferiority established, this exploratory analysis revealed lower rates of the composite of all-cause death or HF events, or MACE-4 among patients with T2D and HF treated with tirzepatide compared with dulaglutide.
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