Selective Serotonin Reuptake Inhibitors Modify the Effect of β-Blockers on Long-Term Survival of Patients With End-Stage Heart Failure and Major Depression

Tousoulis, Dimitris; Antoniades, Charalambos; Drolias, Apostolos; Stefanadi, Elli; Marinou, Kyriakoyla; Vasiliadou, Carmen; Tsioufis, Costas; Toutouzas, Kostas; Latsios, George; Stefanadis, Christodoulos

doi:10.1016/j.cardfail.2008.02.015

« Previous Next »Journal of Cardiac Failure
Volume 14, Issue 6 , Pages 456-464, August 2008

Selective Serotonin Reuptake Inhibitors Modify the Effect of β-Blockers on Long-Term Survival of Patients With End-Stage Heart Failure and Major Depression

Dimitris Tousoulis, MD, PhD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
- Reprint requests: Dimitris Tousoulis, MD, PhD, FACC, Assistant Professor, 1st Cardiology Department University of Athens, Vasilissis Sofias 114, Ampelokipi 115 28, Athens, Greece.
Charalambos Antoniades, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Apostolos Drolias, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Elli Stefanadi, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Kyriakoyla Marinou, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Carmen Vasiliadou, MSc
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Costas Tsioufis, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Kostas Toutouzas, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
George Latsios, MD
- 1st Cardiology Department, Athens University Medical School, Athens, Greece
Christodoulos Stefanadis, MD, FACC, FESC
- 1st Cardiology Department, Athens University Medical School, Athens, Greece

Received 12 November 2007; received in revised form 23 February 2008; accepted 25 February 2008. published online 20 May 2008.

Abstract

Background

Major depression (MD) is a key feature in heart failure (HF), and it is unclear whether common antidepressive medications interact with cardiovascular drugs used for the treatment of patients with MD and HF, affecting their efficacy. We examined the impact of MD on long-term survival of patients with end-stage severe HF. We also evaluated the interaction between antidepressive medication and β-blockers on the clinical outcome of these patients.

Methods and Results

The study population consisted of 250 patients with end-stage severe HF. Sixty-one percent of these patients suffered MD and were receiving selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCA). All patients were followed prospectively for 18 months. The primary end point was cardiovascular death. At baseline, patients with severe MD had higher serum interleukin 6 (P < .05) and soluble vascular cell adhesion molecule (P < .01). During the follow-up, 167 cardiovascular deaths were reported, and MD was 1 of the major predictors of cardiovascular death (P = .031), whereas treatment with angiotensin receptor inhibitors and statins were also important negative predictors of mortality (P = .036 and P = .039, respectively). Although β-blockers had a borderline nonsignificant effect on cardiovascular mortality in the overall population, they had a striking beneficial effect among those patients with major depression receiving SSRIs (P = .006), whereas they had a negative effect on mortality in those patients receiving SNRIs/TCAs (P = .025).

Conclusions

MD is an independent predictor of cardiovascular death in patients with end-stage HF. β-blockers are associated with lower cardiovascular mortality in patients with end-stage HF and depression only when they are combined with SSRIs.

Key Words: Heart failure, depression, inflammation, cardiovascular death, serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors