Impact of comorbidities on safety, tolerability and efficacy of intensified medical therapy in heart failure

Purpose: Investigate the influence of comorbidities on safety, tolerability and efficacy of intensified medical therapy and on overall prognosis in heart failure (HF). Methods: 499 chronic HF patients, age≥60, LVEF≤45%, NYHA class ≥II were randomized to intensified NT-proBNP-guided versus symptom-guided therapy. Patients were clinically followed for 18 months including recording of adverse events (AEs); hospitalizations and mortality and were recorded up to 5 years. Results: Patients had a median Charlson comorbidity score of 3 [IQR 2-4]. Patients with ≥2 comorbidities were older, more often female, had less ischemic origin of HF but higher NYHA classification and NT-proBNP values at baseline. More comorbid patients had a higher incidence of severe AEs including cardiovascular (CV) and HF AEs (fig p-values) but not non-CV AE's. Also, they experienced more AEs per patient-year (5.8 [3.2-11.8] vs 4.0 [2.0-7.0]; P<0.001). Comorbidities interacted with efficacy and tolerability of intensified therapy: positive effects of intensified therapy were observed only in the less comorbid patients, both during the trial (fig *=p for interaction <0.01) and over long-term (HF hospital-free survival HR 0.37 [0.19-0.71]; P=0.003 versus HR=0.87 [0.66-1.14]; P=0.32, P for interaction=0.02) whereas potential negative effects (i.e. hypotension, gout) were only seen in the more comorbid patients. The Charlson comorbidity score was an independent predictor for long-term hospital-free survival (HR=2.47 [1.27-4.83], P<0.001). ![Figure][1] Conclusions: Comorbidities introduce more AEs and a worse prognosis in patients with HF. Interestingly, non-CV AEs are not influenced by comorbidities. Highly comorbid patients did not benefit from intensified medical HF therapy whilst are at higher risk of potential negative effects. [1]: pending:yes