WURZBURG, GERMANY — Use of the selective serotonin-reuptake inhibitor (SSRI) escitalopram does not improve clinical outcomes in patients with both chronic heart failure (CHF) and depression when compared with placebo, suggests research from Germany.
Initial results from the multicenter MOOD-HF trial were presented at the 2015 American College of Cardiology (ACC) Scientific Sessions, as reported by heartwire from Medscape; the full results were published today in the Journal of the American Medical Association.
The study included 372 patients (mean age 62 years) with CHF, reduced LVEF (<45%), and diagnosed depression. It showed that, after a mean of about 18.5 months, 63% of the escitalopram group and 64% of the placebo group died from any cause or were hospitalized (the combined primary outcome).
Severity scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 12 weeks of treatment, while significantly lower than at baseline, were statistically similar for those receiving escitalopram (20.2 at baseline to 11.2) or placebo (21.4 at baseline to 12.5). Also similar were any treatment-related adverse events (46% vs 48%) or serious adverse events (86% vs 80%).
The study "showed that escitalopram was well tolerated but failed to demonstrate a difference between the effects . . . on the elevated mortality and morbidity risk known to be associated with this comorbidity," write the investigators, led by Dr Christiane E Angermann (University Hospital Wurzburg, Germany).
"In addition, the exploratory analysis suggested that remission or improvement of depressive symptoms was not associated with better clinical outcomes," they report.
The researchers note that "compared with the general population, depression is two to three times more common in patients with cardiovascular disease." And a meta-analysis indicates that 10% to 40% of patients with HF have depression.
In addition, early analysis of the OPERA-HF trial showed that HF patients with moderate to severe depression scores were more than five times more likely to die than those with lower scores.
The previously reported SADHART-CHF randomized study showed that use of the SSRI sertraline "did not improve depression or cardiovascular status" vs placebo. But the participants received treatment for only 12 weeks. So for MOOD-HF, the investigators sought to assess longer-term efficacy of an SSRI in this patient population.
The participants were enrolled at one of 16 centers in Germany between March 2009 and February 2014. In addition to receiving heart-failure therapy, all were randomized to receive up to 24 months of either 10 to 20 mg once daily of escitalopram (n=185; mean participation time 18.4 months) or matching placebo (n=187; mean participation time 18.7 months).
The study was terminated early by its steering committee because of futility, with enrollment stopped on February 28, 2014. Still, follow-up was allowed to continue until September 2 of that year.
The adjusted hazard ratio (HR) for the combination of all-cause death or hospitalization between the groups was 0.99 (95% CI 0.77–1.28, P=0.95). The HR for only all-cause death was 1.4 (95% CI 0.69–2.82, P=0.35) and for only all-cause hospitalization was 1.0 (95% CI 0.77–1.29, P>0.99).
For the major secondary end point, the difference in depression scores on the MADRS was -0.9 (95% CI -2.6 to 0.7, P=0.26). Other secondary outcomes also showed no significant between-group differences, with adjusted HRs of 0.91 for CV hospitalization and 0.95 for HF hospitalization (P=0.52 and 0.80, respectively).
Use Not Supported
After the presentation at last year's ACC conference, session moderator Dr Robert J Siegel (Cedars-Sinai Medical Center, Los Angeles, CA) told heartwire that the study raises several questions and noted that the way the investigators classified depression may have had an effect on the findings.
"Post–myocardial-infarction depression . . . might be very different from endogenous depression or other types of depression, where SSRIs have been shown to have benefit," said Siegel at the time. "Also, the effect of depression on mortality is very complex," he said.
He added that the study didn't break out the effects on men vs women or look at different antidepressants.
"There were also extensive safety measures incorporated into the trial design, such as . . . telephone monitoring and psychiatric or psychosomatic expertise (readily available on request)," write the investigators.
"All of these . . . could have blunted between-group difference in outcomes by diminishing treatment effects." Still, the overall findings "do not support the use of escitalopram" in these patients, they conclude.
The study was funded by a grant from the German Ministry of Education and Research and by Lundbeck. Angermann reported receiving grants, personal fees, and nonfinancial support from Lundbeck and ResMed; grants and personal fees from Novartis, Thermo Fisher, Boehringer Ingelheim, and Vifor; personal fees from Servier; nonfinancial support from the University Hospital Wurzburg and the Comprehensive Heart Failure Center Wurzburg; and grants from the German Ministry of Education and Research. Disclosures for the coauthors are listed in the article. Siegel reported at the time of being on the speaker's bureau for Philips Ultrasound.
Heartwire from Medscape © 2016 Medscape, LLC
Cite this: MOOD-HF Results Published: Outcomes Similar for Escitalopram, Placebo in Depression and CHF - Medscape - Jun 28, 2016.