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Original Articles

Prognosis in Heart Failure and the Value of β-Blockers Are Altered by the Use of Antidepressants and Depend on the Type of Antidepressants Used

Emil Loldrup Fosbøl, MB; Gunnar H. Gislason, MD, PhD; Henrik Enghusen Poulsen, MD, DMSc; Morten Lock Hansen, MD; Fredrik Folke, MD; Tina Ken Schramm, MD; Jonas Bjerring Olesen, MB; Ditte-Marie Bretler, MD; Steen Z. Abildstrøm, MD, PhD; Rikke Sørensen, MD; Anders Hvelplund, MD; Lars Køber, MD, DMSc and Christian Torp-Pedersen, MD, DMSc

From the Department of Cardiology (E.L.F., M.L.H., F.F., T.K.S., J.B.O., D.M.B., R.S., A.H., C.T.P.), Gentofte University Hospital, Hellerup, Denmark; The Heart Centre, Department of Cardiology (G.H.G., L.K.), University Hospital of Copenhagen; Department of Clinical Pharmacology (H.E.P.), University Hospital of Copenhagen, Rigshospitalet, Denmark; Faculty of Health Sciences (H.E.P., L.K., C.T.P.), University of Copenhagen, Copenhagen, Denmark; Cardiovascular Research Unit, Department of Internal Medicine (S.Z.A.), University Hospital Glostrup, Glostrup, Denmark; and National Institute of Public Health (S.Z.A., A.H.), Copenhagen, Denmark.

Correspondence to Emil Loldrup Fosbøl, MB, Department of Cardiology, Gentofte University Hospital, Niels Andersens Vej 65, DK 2900 Hellerup, Denmark. E-mail elf{at}heart.dk

Received January 14, 2009; accepted July 30, 2009.

Background— Depression worsens the prognosis in patients with cardiac disease, and treatment with antidepressants may improve survival. Guidelines recommend use of selective serotonin reuptake inhibitors (SSRIs), 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 coadministration of these 2 drug classes was estimated by Cox proportional hazard analyses. Propensity adjusted models were performed as sensitivity analysis. During the study period, there were 53 988 deaths, of which 83.0% were due to cardiovascular causes (median follow-up, 1.9 years; 5, 95% fractiles, 0.04 to 7.06 years). Use of β-blockers was associated with decreased risk of cardiovascular death (hazard ratio [HR], 0.77; 95% CI, 0.75 to 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 to 1.40; and HR, 1.25; CI, 1.17 to 1.32; SSRI: HR, 1.37; CI, 1.34 to 1.40; and HR, 1.34; CI, 1.30 to 1.38, respectively). Coadministration of SSRI and β-blockers was associated with a higher risk of overall and cardiovascular death compared with coadministration of β-blockers and TCA (P for interaction <0.01).

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

Key Words: heart failure • antidepressants • β-blockers • cardiovascular mortality • mortality • pharmacology • depression

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