Effect of implantable cardioverter-defibrillator in non-ischaemic systolic heart failure according to the Heart Failure Collaboratory Medical Therapy Score: extended follow-up of the DANISH trial

Abstract

Abstract Background The Heart Failure Collaboratory (HFC) has developed a medical therapy score which integrates types and doses of guideline-directed pharmacotherapies in patients with systolic heart failure, providing a measure of treatment quality. In clinical trials, this score may help determine the additive effect of new treatments. In the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. Purpose Adding four years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to baseline modified HFC (mHFC) medical therapy score. Methods In the DANISH trial, 1,116 patients with non-ischaemic systolic heart failure were randomised to receive an ICD (N = 556) or usual clinical care (N = 560, control group). The primary outcome was death from any cause. In the mHFC score, patients were assigned a score for each drug class of the original cornerstones of systolic heart failure treatment (renin-angiotensin-system inhibitor, beta-blocker, and mineralocorticoid receptor antagonist). The maximum score was 100%, corresponding to optimal medical therapy with all three types of medication (=>50% of target dose). Results The median mHFC score at baseline was 67% (25th-75th percentile, 67%-100%; range, 17%-100%). During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74-1.08]). The results were independent of the mHFC score at baseline (mHFC score = < median: HR 0.91 [95% CI, 0.70-1.19]; mHFC score > median: HR 0.87 [95% CI, 0.66-1.14]; P for interaction, 0.94). Similarly, ICD implantation did not reduce the rate of cardiovascular death overall (HR 0.87 [95% CI, 0.70-1.09]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.90 [95% CI, 0.65-1.24]; mHFC score > median: HR 0.84 [95% CI, 0.61-1.15]; P for interaction, 0.89). The ICD group had a significantly lower rate of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40-0.92]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.72 [95% CI, 0.40-1.29]; mHFC score > median: HR 0.53 [95% CI, 0.28-0.99]; P for interaction, 0.59). See Figure for results. Conclusions In this extended follow-up study of the DANISH trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure regardless of baseline medical heart failure therapy, assessed by the mHFC score.Modified HFC score in the DANISH trial