Phosphodiesterase type 5 inhibitors as adjunctive therapy in the management of systolic heart failure.

OBJECTIVE: To review the efficacy and safety of phosphodiesterase-5 (PDE5) inhibitors in the treatment of patients with chronic systolic heart failure (HF).

DATA SOURCES: Literature was retrieved through MEDLINE (1966-September 2011) and EMBASE (1980-September 2011), using the medical subject heading terms heart failure and phosphodiesterase-5 inhibitors, sildenafil, tadalafil, and vardenafil. Focus was placed on multidose trials of patients with systolic HF, because of these trials' greater strength of clinical evidence.

STUDY SELECTION AND DATA EXTRACTION: All English-language, peer-reviewed publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 4 multidose trials investigating the effect of sildenafil on cardiovascular function.

DATA SYNTHESIS: In patients with New York Heart Association class II or III HF, treatment with sildenafil was associated with improvements in cardiac index, right ventricular ejection fraction, and other markers of cardiovascular function, as well as reduced pulmonary arterial pressure. Study durations ranged from 4 weeks to 1 year, and the studies used varying doses of sildenafil, ranging from 75 to 225 mg/day, in divided doses. The most common adverse effects associated with sildenafil therapy were headache and flushing.

CONCLUSIONS: Based on current studies, sildenafil appears to be well tolerated and can improve markers of cardiovascular and pulmonary function in patients with HF. PDE5 inhibitors may be a therapeutic option for patients who cannot tolerate standard therapy for HF or who remain symptomatic with standard therapy. Larger long-term trials are necessary to better understand the role of PDE5 inhibitors in HF.