Tirzepatide Shows Consistent Cardiovascular Benefits Regardless of Heart Failure Status in SURPASS-CVOT Trial
Key Insights
Tirzepatide demonstrated similar cardiovascular benefits to dulaglutide in patients with type 2 diabetes (search), regardless of whether they had a history of heart failure (search).
The drug showed superior outcomes for all-cause death and heart failure (search) hospitalizations compared to dulaglutide in both patient groups with and without heart failure.
Results from the SURPASS-CVOT trial suggest tirzepatide's cardiovascular protective effects are consistent across different heart failure (search) populations.
Tirzepatide demonstrated consistent cardiovascular benefits in patients with type 2 diabetes (search) regardless of their heart failure (search) status, according to a prespecified analysis of the SURPASS-CVOT trial presented at the American Heart Association Scientific Sessions in New Orleans.
The analysis, led by Stephen J. Nicholls from Monash University in Melbourne, Australia, examined outcomes in 13,165 participants with type 2 diabetes (search) and atherosclerotic cardiovascular disease (search) who were randomly assigned to receive either tirzepatide (maximum tolerated dose of 5 mg, 10 mg, or 15 mg once weekly) or dulaglutide (1.5 mg once weekly) over a median follow-up period of 4 years.
Superior Outcomes in Heart Failure-Related Events
While tirzepatide showed non-inferiority to dulaglutide for most cardiovascular outcomes, it demonstrated superiority in specific heart failure (search)-related endpoints. For all-cause death or hospitalization/urgent visit for heart failure, tirzepatide showed consistent benefits regardless of heart failure history: patients with prior heart failure had a hazard ratio of 0.83 (95% CI, 0.7-0.99), while those without prior heart failure had a hazard ratio of 0.88 (95% CI, 0.78-1), with no significant interaction between groups (P = 0.63).
Similarly, for all-cause death alone, tirzepatide was superior to dulaglutide in both populations: hazard ratio of 0.8 (95% CI, 0.65-0.97) in patients with prior heart failure (search) and 0.86 (95% CI, 0.75-0.99) in those without prior heart failure (P for interaction = 0.5).
Consistent Metabolic Benefits Across Groups
Approximately 20% of the study cohort had a history of heart failure (search), and these patients were more likely to have prior myocardial infarction (search) and hypertension (search) compared to those without heart failure history. Despite these baseline differences, tirzepatide consistently demonstrated greater reductions in blood pressure, HbA1c, and body weight compared to dulaglutide, regardless of heart failure status.
The drug also showed less reduction in estimated glomerular filtration rate compared to dulaglutide, with this benefit observed consistently across both heart failure (search) groups.
Primary and Secondary Endpoint Analysis
For the primary endpoint of cardiovascular death, myocardial infarction (search), or stroke (search), tirzepatide performed similarly to dulaglutide in both patients with and without prior heart failure (search). However, the secondary endpoint of cardiovascular death, myocardial infarction, stroke, or coronary revascularization favored tirzepatide in both groups.
Nicholls noted that the benefit of tirzepatide "looks like it is all on fatal events, with there being no difference in terms of nonfatal heart failure (search) outcomes" in both patient populations.
Safety Profile and Clinical Implications
Adverse event rates between tirzepatide and dulaglutide did not vary by heart failure (search) status. The higher rate of gastrointestinal adverse events with tirzepatide was observed consistently in both patients with and without heart failure history.
During the trial, patients in the dulaglutide group were more likely to initiate SGLT2 inhibitor therapy compared to those receiving tirzepatide, though the clinical impact of this difference remains unclear.
Future Research Directions
John J.V. McMurray from the University of Glasgow, serving as a discussant, emphasized the need for dedicated morbidity and mortality trials in well-characterized heart failure (search) populations. He advocated for studies in both heart failure with preserved and reduced ejection fraction, across obese and non-obese patients, and in those with and without type 2 diabetes (search).
"These drugs reduce cardiovascular mortality in patients with obesity (search)," McMurray stated. "It would be a terrible pity if we missed the opportunity to potentially reduce cardiovascular mortality in patients with heart failure (search) and reduced ejection fraction, with perhaps the highest cardiovascular mortality risk in all patients that we treat in the whole of cardiology."
The findings suggest that tirzepatide's cardiovascular protective effects extend consistently across different heart failure (search) populations, potentially offering clinicians confidence in prescribing the medication regardless of patients' heart failure status.