Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Abstract

Background: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence based drug therapies that reduce mortality. Objective: This systematic review and meta-analysis aims to assess whether sildenafil reduces mortality, reduces disease progression and the adverse side effects associated with it. Methods: In this review, randomized controlled studies (RCTs) were retrieved from MEDLINE, Cochrane, and EMBASE. The primary outcome was mortality. The secondary outcomes included change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance random effects meta-analysis method to calculate pooled odds ratio (OR) and standardized mean difference (SMD). Results: A total of 4 studies were included. Sildenafil probably reduces mortality when compared to placebo or to standard care, [OR 0.63 (0.38,1.03), I2=0%]. Pooled results showed sildenafil does not alter the rate of change of FVC [SMD 0.02 (-0.14,0.18)], or DLCO [SMR -0.01 (-0.18,0.17)], I2=0]. Pooled results showed sildenafil may not reduce the number of hospitalizations or acute exacerbations, [OR 1.06 (0.67,1.67)], I2= 0]. There was no significant difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [OR 0.79 (0.56, 1.11)], I2=0]. Conclusion: Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done in order to confirm the magnitude and reliability of the point estimate.

PDE5 to keep them alive: The use of phosphodiesterase type‐5 inhibitors in severe pulmonary hypertension associated with interstitial lung disease

“…Thus, their data suggest that PDE5i might improve survival in patients with ILD and severe PH and that an individualized trial of PDE5i (with continuation in those who respond) is a reasonable approach in expert PH centres (Figure 1). Clinicians following this approach might be reassured by a meta‐analysis of the aforementioned sildenafil trials, which suggested a potential mortality benefit in the overall IPF population and an unlikely signal for harm 12 . However, given the limitations and biases inherent to retrospective observational analyses and issues arising from the populations included in the previous trials of PDE5i in ILD, we wish to underscore the need for a future randomized placebo‐controlled trial of PDE5i in a population enriched for severe PH, and possibly stratified by the presence of RV dysfunction at baseline.…”