Phosphodiesterase 5 inhibitors for the treatment of heart failure: a systematic review and meta-analysis

Ramiro Monzón-Herrera, Servicio de Cardiología, Hospital de Alta Complejidad en Red El Cruce, Florencio Varela, Buenos Aires, Argentina
Federico Listorti, Servicio de Cardiología, Hospital de Alta Complejidad en Red El Cruce, Florencio Varela, Buenos Aires, Argentina
Natalia Vensentini, Servicio de Cardiología, Hospital de Alta Complejidad en Red El Cruce, Florencio Varela, Buenos Aires, Argentina
Javier Mariani, Servicio de Cardiología, Hospital de Alta Complejidad en Red El Cruce; Universidad Arturo Jauretche. Florencio Varela, Buenos Aires, Argentina

Objective: The treatment with phosphodiesterase-5 (PDE-5) inhibitors was postulated in heart failure (HF). We conducted a systematic review and a meta-analysis on their beneficial and adverse effects in patients with HF. Method: A meta-analysis of randomized trials evaluating the chronic use of PDE-5 inhibitors in patients with HF was conducted. Endpoints included death, HF hospitalizations, functional capacity, pulmonary pressures, quality of life, and adverse effects. Random-effects models were used to pool outcomes. Categorical data were summarized with relative risks (RR) and 95% confidence intervals (95%CI), and continuous data with weighted mean differences and standardized mean differences. Results: Sixteen studies (1119 participants) were included. No effect was observed on mortality (RR: 1.16; 95%CI: 0.50-2.66; I2: 0.0%) or HF hospitalizations (RR: 0.75; 95%CI: 0.41-1.37; I2: 38.7%). Treatment significantly reduced pulmonary systolic pressure (−10.64 mmHg; 95%CI: −5.14 to −16.15 mmHg; I2: 96.0%), and increased peak oxygen consumption (2.06 ml/kg/min; 95%CI: 0.40-3.72; I2: 89.6%), although with high inconsistency. There were no significant effects on quality of life (−0.15; 95%CI: −0.48-0.18; I2: 0.0%). On the other hand, the risk of headaches was increased (RR: 1.63; 95%CI: 1.11-2.39; I2: 0.0%). Publication bias was identified for HF hospitalizations. Conclusions: Current data suggest that PDE-5 inhibitors therapy does not improve prognosis or quality of life among HF patients. Hemodynamic and functional effects could be relevant, and more studies are necessary to define its role.

Keywords: Heart failure. Phosphodiesterase-5 inhibitors. Mortality. Pulmonary hypertension. Quality of life. Systematic review.