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

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.