Background:
Affective disorders such as major depressive disorder (MDD) are common in patients with heart failure (HF) and associated with adverse prognosis. Potential mechanisms relating MDD with HF pathophysiology include alterations of the hypothalamic-pituitary-adrenal (HPA) axis. Circadian salivary cortisol levels (SCL) are established markers of HPA axis activity. In the randomized MOOD-HF trial antidepressant therapy with escitalopram (E) did neither ameliorate MDD nor improve outcomes compared to placebo (P). However, subgroup analysis suggested adverse side effects of E.
Aims:
The MOOD-HF SCL substudy explored the interrelation of circadian SCL changes on effects of E vs. P in patients with HF. The current analysis sought to clarify, whether the frequency of serious adverse clinical events (SAE) during treatment with E vs. P depended on baseline (BL) evening SCL (ESCL).
Methods:
Patients with symptomatic HF (left ventricular ejection fraction <45%) were eligible for MOOD-HF if suffering from current MDD (structured clinical interview). Patients were randomized 1:1 to either E, 10-20 mg once daily, or matching P. Medical HF therapy was optimized in both study arms. Patients providing samples for ESCL assessment at BL (commercial luminescence immunoassay IBL, Hamburg, Germany) and not on oral steroids were eligible for the present analysis. SAE were recorded during 12 months’ treatment and analysed in subgroups by ESCL and study medication.
Results:
Of 372 MOOD-HF participants, 293 (62 ±12 years, 75% male, E: n=146; P: n=147) qualified for the present analysis. BL characteristics including ESCL were similar between study arms (median (IQR) in E: 0.07 [0.040.13] µg/dL; P: 0.07 [0.03-0.13] µg/dL, respectively, p= 0.68). During 12 months’ follow-up, 16 patients died (9 on E, 7 on P) and 134 were hospitalized at least once (83 on E, 81 on P). Numerically, patients with ESCL ≥ global median had consistently higher SAE rates than patients with lower ESCL, but only in patients treated with E this difference reached statistical significance across all SAE categories (Table). A significant ESCL x treatment interaction was found for non-cardiovascular (CV) SAE (including also hospitalizations for depression) only.
Conclusion:
In patients with systolic HF and comorbid MDD ESCL ≥ median were associated with higher SAE risk which reached significance in those treated with E. ESCL may prove a valuable biomarker for risk assessment when considering antidepressant therapy with E in HF populations.