Key Points
- In SURPASS-CVOT, tirzepatide was previously shown to be non-inferior to dulaglutide for 3-point major adverse cardiovascular events (MACE-3) in adults with type 2 diabetes and atherosclerotic cardiovascular disease, with a hazard ratio of 0.92 (95% CI 0.83–1.01) and all-cause mortality of 0.84 (95% CI 0.75–0.94).
- In this prespecified analysis of 13,000+ participants, tirzepatide reduced the composite of all-cause death or heart-failure events to 10.5% versus 12.1% with dulaglutide (HR 0.86, 95% CI 0.77–0.95), with a stronger effect in the 20% of patients who had established heart failure at baseline.
- Among patients with prior heart failure, tirzepatide was associated with lower all-cause death (HR 0.80, 95% CI 0.65–0.97), fewer MACE-4 events (HR 0.81, 95% CI 0.69–0.95), and fewer coronary revascularizations (HR 0.76, 95% CI 0.59–0.98) compared with dulaglutide, while rates of heart-failure hospitalization alone were similar between groups.
Building on the primary results of SURPASS-CVOT, investigators have now turned their attention to patients with co-existing heart failure, a subgroup that carries particularly high residual risk despite contemporary therapies. The new prespecified analysis, presented at the AHA 2025 Annual Meeting, evaluated whether tirzepatide confers additional benefit over dulaglutide on death, atherosclerotic events, and heart-failure outcomes in patients with and without heart failure at baseline.
SURPASS-CVOT enrolled adults with type 2 diabetes and established atherosclerotic cardiovascular disease, randomizing them to tirzepatide (up to 15 mg) or dulaglutide 1.5 mg. For this analysis, patients were stratified according to a history of heart failure. The key endpoint was time to first occurrence of a composite of all-cause death or heart-failure events, defined as hospitalization or urgent visits for heart failure; additional outcomes included cardiovascular death, individual heart-failure events, MACE-3, and the 4-point composite MACE-4, which adds coronary revascularization to MACE-3.
Overall, the composite of all-cause death or heart-failure events occurred less frequently with tirzepatide than with dulaglutide (10.5% vs 12.1%; HR 0.86, 95% CI 0.77–0.95). Of the 13,000-plus participants, 2,678 (20.3%) had a history of heart failure at baseline. This subgroup was more burdened by coronary disease than those without heart failure, with higher rates of prior coronary artery disease (77.6% vs 61.8%) and previous myocardial infarction (57.8% vs 44.5%).
In patients with established heart failure, tirzepatide consistently favored improved outcomes. The composite of all-cause death or heart-failure events occurred in 18.2% of tirzepatide-treated patients versus 21.5% with dulaglutide (HR 0.83, 95% CI 0.70–0.99). Cardiovascular death or heart-failure events showed a similar trend (14.4% vs 16.7%; HR 0.85, 95% CI 0.70–1.03). All-cause mortality alone was reduced from 16.7% with dulaglutide to 13.5% with tirzepatide (HR 0.80, 95% CI 0.65–0.97). While hospitalization or urgent visits for heart failure were numerically similar (7.6% vs 7.7%; HR 0.97, 95% CI 0.73–1.27), ischemic outcomes appeared more clearly impacted: MACE-4 occurred in 20.5% versus 24.7% (HR 0.81, 95% CI 0.69–0.95), and coronary revascularization in 7.9% versus 10.1% (HR 0.76, 95% CI 0.59–0.98) with tirzepatide versus dulaglutide, respectively. Patients without a history of heart failure also tended to benefit. In this larger subgroup, tirzepatide reduced the composite of all-cause death or heart-failure events from 9.7% to 8.6% (HR 0.88, 95% CI 0.78–1.00) and lowered all-cause mortality (7.4% vs 8.4%; HR 0.86, 95% CI 0.75–0.99). Effects on MACE-3, MACE-4, and coronary revascularization in the no-heart-failure cohort were directionally consistent with those seen in patients with heart failure, with hazard ratios generally below 1.0.
According to Dr. Stephen Nicholls and his team, these findings suggest that tirzepatide may offer broader protection than dulaglutide across the spectrum of patients with type 2 diabetes, atherosclerotic cardiovascular disease, and heart failure, primarily by reducing death and ischemic events rather than heart-failure hospitalizations alone. As clinicians weigh options among incretin-based therapies for high-risk patients, the heart-failure–focused data from SURPASS-CVOT add to the emerging picture of tirzepatide’s cardiometabolic profile.
