Long-Term Mortality Associated with Use of Carvedilol vs Metoprolol in Heart Failure Patients with and Without Type 2 Diabetes

Background: Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2DM) and heart failure with reduced ejection fraction (HFrEF). Methods and Results: Using Danish nationwide databases between 2010-2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39,260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9,355 (24%) had T2DM. Carvedilol was used in 2,989 (32%) patients with TD2M and 10,411 (35%) of patients without T2DM. Users of carvedilol had a lower prevalence of atrial fibrillation (20% vs. 35%), but other characteristics appeared well-balanced between the groups. Totally 11,306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazards ratio 0.97 (0.90-1.05) in patients with T2DM versus 1.00 (0.95-1.05) for those without T2DM, p for difference =0.99. Rates of new-onset T2DM were lower in users of carvedilol vs. metoprolol; age, sex, and calendar year adjusted hazards ratio 0.83 (0.75-0.91), p<0.0001. Conclusion: In a contemporary clinical cohort of HFrEF patients with and without T2DM, carvedilol was not superior to metoprolol for long-term mortality reduction. However, carvedilol was associated with lowered risk of new-onset T2DM supporting the assertion that carvedilol have a more favorable metabolic profile than metoprolol overall.