Published Online
on September 22, 2009

A more recent version of this article appeared on November 1, 2009

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Original Article

Prognosis in Heart Failure and the Value of Beta-blockers are Altered by the Use of Antidepressants and Depend on the Type of Antidepressants Used

Emil Loldrup Fosbøl^1,7; Gunnar Hilmar Gislason²; Henrik Enghusen Poulsen³; Morten Lock Hansen¹; Fredrik Folke¹; Tina Ken Schramm¹; Jonas Bjerring Olesen¹; Ditte-Marie Bretler¹; Steen Z Abildstrøm⁴; Rikke Sørensen¹; Anders Hvelplund⁵; Lars Køber⁶ and Christian Torp-Pedersen³

¹ Gentofte University Hospital, Hellerup, Denmark;
² University Hospital of Copenhagen, Rigshospitalet, Denmark;
³ Gentofte University Hospital, Hellerup and University of Copenhagen, Copenhagen, Denmark;
⁴ University Hospital Glostrup and National Institute of Public Health, Copenhagen, Denmark;
⁵ Gentofte University Hospital, Hellerup and National Institute of Public Health, Copenhagen, Denmark;
⁶ University Hospital of Copenhagen, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

^* Corresponding author; email: elf{at}heart.dk

Background—Depression worsens the prognosis in patients with cardiac disease and treatment with antidepressants may improve survival. Guidelines recommend use of serotonine reuptake inhibitors (SSRI); but knowledge of the prognostic effect of different classes of antidepressants is sparse.

Methods and Results—We studied 99,335 patients surviving first hospitalization for heart failure (HF) from 1997 to 2005. Use of HF medication and antidepressants (divided into tricyclic antidepressants (TCA) and SSRI) was determined by prescription claims. Risk of overall and cardiovascular death associated with antidepressants, HF medication and co-administration of these two drug-classes was estimated by Cox proportional hazard analyses. Propensity adjusted models were performed as sensitivity analysis.<br> In the study period there were 53,988 deaths of which 83.0% were from cardiovascular causes (median follow-up 1.9 years 5, 95% fractiles 0.04-7.06 years). Use of beta-blockers was associated with decreased risk of cardiovascular death (hazard ratio (HR)=0.77, 95% confidence interval (CI): 0.75-0.79). Antidepressants were prescribed to 19,411 patients, and both TCA and SSRI were associated with increased risk of overall and cardiovascular death (TCA: HR=1.33, CI: 1.26-1.40 and HR=1.25, CI: 1.17-1.32 and SSRI: HR=1.37, CI: 1.34-1.40 and HR=1.34, CI: 1.30-1.38, respectively). Co-administration of SSRI and beta-blockers was associated with a higher risk of overall and cardiovascular death compared with co-administration of beta-blockers and TCA (p for interaction <0.01).

Conclusions—Use of antidepressants in patients with HF was associated with worse prognosis. Co-administration of SSRIs and beta-blockers was associated with increased risk of overall death and cardiovascular death compared with co-administration of TCAs and beta-blockers. To further clarify this, clinical trials testing the optimal antidepressant strategy in HF patients are warranted.

Key Words: heart failure • pharmacology • antidepressants • depression