Adherence and Discontinuation of Optimal Heart Failure Therapies According to Age: A Danish Nationwide Study

Background Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. Methods and Results Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51-1.69]; BB 1.33 [95% CI, 1.25-1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). Conclusions In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.