Therapeutic benefits of phosphodiesterase-5 inhibition in chronic heart failure: A meta-analysis

BACKGROUND: Phosphodiesterase-5 inhibitors (PDE5i) have been shown to be beneficial for patients with pulmonary arterial hypertension. However, several studies would have documented a useful effect of PDE5i even for pulmonary hypertension secondary to left-sided chronic heart failure (CHF). METHODS: We performed a meta-analysis including randomized controlled trials (RCTs) which had compared PDE5i (mostly sildenafil) and placebo in CHF patients. RESULTS: Fourteen studies enrolling a total of 928 patients were incorporated in the meta-analysis. In heart failure with reduced left ventricular ejection fraction (HFREF), PDE5i, compared to placebo, significantly improved the composite of death and hospitalization (OR = 0.28; 95% CI: 0.10–0.74). They also improved peak VO(2) [difference in means (MD): 3.76; 95% CI: 3.27–4.25], six-minute walking distance test (MD: 22.7 m; 95% CI: 8.19–37.21), and pulmonary arterial systolic pressure (MD: −11.52 mmHg; 95% CI: −15.56 to −7.49). Conversely, in CHF with preserved left ventricular ejection fraction (HFpEF), PDE5i proved not to yield any significant improvement of the investigated outcomes. CONCLUSIONS: In HFREF, PDE5i showed beneficial effects on the composite of death and hospitalization, as well as on exercise capacity and pulmonary hemodynamics. Conversely, in HFpEF, no significant clinical, spiroergometric, or hemodynamic improvement was achieved using PDE5i therapy.