Effect of comorbidities on outcomes and angiotensin converting enzyme inhibitor effects in patients with predominantly left ventricular dysfunction and heart failure

Aims: Comorbidities are frequent in heart failure and impact outcomes. It is not known whether comorbidities are associated with outcomes in asymptomatic left ventricular dysfunction compared to clinical heart failure and whether comorbidities interfere with treatment effects. Our objective was to assess comorbidities and their effects on outcomes in predominantly asymptomatic populations without previous heart failure treatment of the SOLVD prevention trial, compared to symptomatic heart failure patients of SOLVD treatment and to evaluate associations to the effect of enalapril.

Methods and results: This post hoc analysis from the SOLVD prevention and SOLVD treatment trials includes 4228 patients with left ventricular dysfunction and 2569 patients with heart failure. The preexisting comorbidities hypertension, diabetes mellitus, pulmonary disease, angina pectoris, renal impairment, and anaemia were similar in SOLVD treatment and SOLVD prevention, with a higher prevalence in SOLVD treatment. Comorbidities are significantly associated with the primary composite of SOLVD time to death or heart failure hospitalization (SOLVD prevention: HR 4.8, CI: 3.2-7.18, P < 0.0001; SOLVD treatment: HR 2.9, CI: 2.12-3.95, P < 0.0001 for more than four comorbidities vs. no comorbidities), and to death, heart failure hospitalization, and cardiovascular death where the effect of the number of coexisting comorbidities was additive. There was no significant interaction of comorbidities with treatment effects of enalapril.

Conclusion: Comorbidities increased events in asymptomatic left ventricular dysfunction and in symptomatic heart failure, but did not interfere with the effects of enalapril. Comorbidities need to be adequately addressed in clinical trials, which should also involve non-cardiac treatments in order to improve outcome for heart failure patients.