Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial

Abstract

Objectives: The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo.

Background: Depression is common among HF patients. It is associated with increased hospitalization and mortality.

Methods: The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks.

Results: A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78).

Conclusions: Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Figure 1. Participant Flow Through the Trial

Completers were participants who completed 12-weeks of study drug and assessment at the end of the 12-week intervention. Non-completers were participants who discontinued study drug prior to 12-weeks. Participants were considered non-compliant if they did not take the study medication for ≥14 consecutive days.

Figure 2. Change in HDRS from Baseline to Week 12

Based on raw HDRS scores. This plot displays the change in HDRS total scores by week in the study. The primary analysis was conducted based on the natural log of days, with a P=.89.