EFFICACY OF PHOSPHODIESTERASE-5 INHIBITOR IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: A META-ANALYSIS

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a common health problem and a major cause of mortality and morbidity. The prognosis worsens with pulmonary hypertension and right sided heart failure. Sildenafl is a phosphodiesterase-5 inhibitor (PDF5I), which selectively reduces pulmonary vascular resistance and is recognized as an effective therapy for pulmonary artery hypertension. The literature evaluating the effect of siladenafl in HFpEF is scant and lacks precision in view of the small patient size. We performed a meta-analysis to evaluate the effcacy of sildenafl on hemodynamic parameters in patients with HFpEF. Methods: A systematic search of databases, including Pubmed, Web of Science, Google scholar and Cochrane Database was performed by two independent reviewers to identify relevant studies. Studies comparing PDF5I sildanefl versus placebo, with minimum duration of treatment of at least 9 weeks in patients with HFpEF were included. The primary outcome measure was pulmonary artery systolic pressure (PASP) and secondary outcomes were cardiac index (CI), right atrial pressure (RAP), peak oxygen consumption (pVo2), and serious adverse events. Results: Four randomized controlled studies with a total of 379 patients were included in the analysis. Random-effects method was used. There were no signifcant differences in PASP (WMD, -5.22 [CI -16.26, 5.81], I2= 99%), CI (WMD, 1.79 [CI -0.91,4.50], I2= 99%), RAP (WMD, -2.45 [CI -7.11,2.20], I2= 95%) and pVO2 (OR, 0.20 [CI 0.09,0.31], I2= 0%). There were a total of 12.8% serious adverse events for the total duration of follow up. There was no signifcant difference in the rate of serious adverse events between the two groups (OR, 1.51 [CI 0.77,2.96], I2= 0%). Publication bias calculated from PASP analysis showed asymmetry in the funnel plot indicates publication bias. Conclusions: In patients with HFpEF, Sildenafl did not result in signifcant improvement in hemodynamic parameters. More randomized controlled trials are needed to defne the role of sildenafl in HFpEF.