The Impact of Depression on Outcomes in Patients With Heart Failure and Reduced Ejection Fraction Treated in the GUIDE-IT Trial.

BACKGROUND:It remains unclear why depression is associated with adverse outcomes in patients with heart failure (HF). We examine the relationship between depression and clinical outcomes among patients with HF with reduced ejection fraction managed with guideline-directed medical therapy (GDMT). METHODS AND RESULTS:Using the GUIDE-IT trial, 894 patients with HF with reduced ejection fraction were stratified according to a history of depression, and Cox proportional hazards regression modeling was used to examine the association with outcomes. There were 140 patients (16%) in the overall cohort who had depression. They tended to be female (29% vs 46%, P < .001) and White (67% vs 53%, P = .002). There were no differences in GDMT rates at baseline or at 90 days; nor were there differences in target doses of these therapies achieved at 90 days (NS, all). amino-terminal pro-B-type natriuretic peptide levels at all time points were similar between the cohorts (P > .05, all). After adjustment, depression was associated with all-cause hospitalizations (hazard ratio, 1.42, 95% confidence interval 1.11-1.81, P < .01), cardiovascular death (hazard ratio, 1.69, 95% confidence interval 1.07-2.68, P = .025), and all-cause mortality (hazard ratio, 1.54, 95% confidence interval 1.03-2.32, P = .039). CONCLUSIONS:Depression impacts clinical outcomes in HF regardless of GDMT intensity and amino-terminal pro-B-type natriuretic peptide levels. This finding underscores the need for a focus on mental health in parallel to achievement of optimal GDMT in these patients. TRIAL REGISTRATION:NCT01685840, https://clinicaltrials.gov/ct2/show/NCT01685840.