Depression, antidepressants, and long-term mortality in heart failure

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Abstract

Background

This study was designed to assess whether depression and the use of antidepressants were related to long-term mortality in heart failure.

Methods

Heart failure outpatients (n = 1017) from a specialized tertiary unit in Spain were prospectively studied for a median follow-up of 5.4 years (IQR 3.1–8.1). Depressive symptoms were assessed using an abbreviated version of the geriatric depression scale. Survival rates during the study period (August 2001 until December 2010) and hazard ratios (HR) for mortality were adjusted by several demographic and clinical variables.

Results

Depressive symptoms were detected in 302 patients (29.7%) at baseline and 222 (21.8%) de novo during follow-up; 304 patients (29.9%) received at least one prescription of antidepressants, mainly selective serotonin reuptake inhibitors (92.8%); 441 patients (43.4%) died. In a multivariate Cox proportional hazard model, depression was associated with an increased all-cause (HR, 1.39; 95% CI, 1.15–1.68), but not cardiovascular, mortality risk after adjustment for several demographic and clinical confounders. The use of any antidepressant was not independently associated with mortality (HR, 0.89; 95% CI, 0.71–1.13), but benzodiazepines showed a protective role (HR, 0.70; 95% CI, 0.57–0.87). On the contrary, fluoxetine prescriptions, but not duration of fluoxetine treatment, were associated with increased mortality (HR, 1.66; 95% CI, 1.13–2.44).

Conclusions

Depressive symptoms are associated with long-term mortality, but the use of antidepressants and benzodiazepines is safe regarding survival in HF patients, although further research is needed considering individual antidepressants separately.

Introduction

Chronic heart failure (HF) is a prevalent disease in the general population, affecting 8–17% of people over 70 years of age. The average mortality rate is high, approximately 10% one year after diagnosis and increasing to 50% after 5 years [1].

Prevalence of depression in HF patients is high, ranging between 11% and 51% [2], [3], [4]. Rates vary depending on the diagnostic instrument used, the severity threshold of depressive symptoms to make the diagnosis, and the type of population assessed.

Depression has been associated with worse outcomes and higher rates of mortality in several cohorts of patients with HF, even adjusting for clinical and biological variables of HF severity [3], [4], [5], [6], [7], [8], [9], [10], [11]. Increased depression severity is related with higher rates of short-term mortality [12]. However, fewer studies have focused on the impact of depression on long-term mortality, with only four studies with a follow-up period of more than 5 years [13], [14], [15], [16]. Moreover, the prognostic power of depression to predict mortality seems to increase over time [17].

Remission of depression seems to be related to an improvement on survival [18], but the benefits of antidepressant treatments on HF outcomes are not well known. Selective serotonin reuptake inhibitors (SSRIs) have been shown to inhibit platelet function, promote endothelial stabilization, and possess antiinflammatory properties, although the clinical relevance of these properties has yet to be established [19]. Nevertheless, some observations have indicated that the use of antidepressants can be associated with an increased likelihood of death or cardiovascular hospitalization [8], [20], [21]. Other studies have failed to find such association when controlling data for the impact of depression and other variables [4], or even have showed a protective role for antidepressants [22], [23], and a recent double-blind trial has found sertraline to be safe in patients with HF [24].

The aim of the present study was to evaluate the effect of depressive symptoms on mortality in a cohort of chronic HF outpatients followed in a specialized tertiary unit, as well as the influence of the naturalistic use of antidepressants in this population.

Section snippets

Patients

All patients with established HF, diagnosed according to the European Society of Cardiology criteria [25], regardless of etiology, aged over 18 years, and admitted to a specialized HF outpatient Unit of a University Hospital in Barcelona (Spain) between 1 August 2001 and 31 December 2009 were included in the study. At first visit, patients provided informed consent for using their clinical data for research purposes. All study procedures were in accordance with ethical standards outlined in the

Results

Along the recruitment period, 1101 patients were admitted to the HF Unit. Twenty-one patients (1.9%) were excluded because of incomplete clinical data and 63 (5.7%) because of moderate to severe cognitive impairment (Pfeiffer test > 4). The remaining 1017 patients were followed for a median of 5.4 years (interquartile range 3.1–8.1 years) (Fig. 1). Ninety-eight percent of the patients were white. Table 1 shows demographic and clinical characteristics of the sample.

Discussion

We have presented prospective data on the relationship between mortality outcomes, depressive symptoms, and the use of antidepressants and benzodiazepines in a large sample of HF patients from a tertiary specialized unit, and with a long follow-up period (median 5.4 years). Moreover, the use of a very brief instrument to detect depressive symptoms (GDS-4) adds value as it would be more practical in clinical settings. Anywhere, replication is needed to confirm that brief, practical depression

Acknowledgments

Author contributions: All authors had full access to all the data and take responsibility for the integrity and accuracy of the data analyses.

Study concept and design: Diez-Quevedo, Lupón, and Bayes-Genis.

Acquisition of data: Diez-Quevedo, Gonzalez, Cano, and Cabanes.

Analysis and interpretation of data: Diez-Quevedo, Lupón, Urrutia, Altimir, Coll, Pascual, de Antonio, and Bayes-Genis.

Drafting of the manuscript: Diez-Quevedo, Lupón, and Bayes-Genis.

Critical revision of the manuscript for

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    Preliminary findings of this paper were presented at the Heart Failure Congress 2011, Gothenburg — Sweden, 23 May 2011, and the European Society of Cardiology Congress 2011, Paris — France, 30 Aug 2011.

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