Introduction: Diabetes mellitus (DM) is a common co-morbidity in patients with heart failure and reduced left ventricular ejection fraction (HF-REF), and is associated with adverse prognosis. Subgroup analyses of randomized controlled trials suggest patients with DM benefit prognostically from beta-adrenoreceptor blockers (BB) and angiotensin converting enzyme inhibitors (ACEi). However, it remains unclear whether escalating doses of these agents are associated with similar benefit in people with DM.
Hypothesis: Escalating doses of BB and ACEi are associated with similar mortality reduction in HF-REF patients with and without DM.
Methods: Prospective cohort study of 1802 patients with stable HF-REF, recruited from 4 UK hospital clinics between 2006 and 2014. Mortality data was available in all patients after a mean 4-year follow-up period. Prescribed BB dose was expressed as the equivalent daily dose of bisoprolol, and ACEi dose as the equivalent daily dose of ramipril. Cox regression analysis was used to define the interaction between DM and BB or ACEi dose.
Results: 28% of patients had DM; they received similar doses of BB and ACEi to patients without DM, and had comparable resting heart rate. Every milligram increment in BB dose was associated with a 3.5% (95% CI 0.76.3%; P=0.015) reduction in mortality in patients without DM, and an 8.9% (95% CI 512.6%; P<0.001) reduction in patients with DM (interaction P=0.027). This interaction persisted in multivariate regression analysis accounting for other prognostically important factors. A similar interaction was in analyses restricted to progressive heart failure death, or sudden cardiac death. Whilst rising ACEi dose was also associated with lower mortality, no interaction with DM status was found.
Conclusion: Escalating BB, but not ACEi, dose is associated with greater all-cause and mode-specific reductions in mortality in patients with DM.