Sunday, 14 August, 2022
HomePulmonologyViagra may reduce pulmonary fibrosis mortality – Canadian meta-analysis

Viagra may reduce pulmonary fibrosis mortality – Canadian meta-analysis

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalisations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil (in IPF) and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” said Dr Tyler Pitre, McMaster University, Hamilton, Ontario and Dena Zeraatkar, PhD, Harvard Medical School, Boston.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so re-analysis of the data was felt to be necessary to inform upcoming guidelines.

The purpose of the review was to provide an update of the evidence of whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalisations, along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomised, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev).

The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalisations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalisations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty.

Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients.

Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Study details

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

Tyler Pitre, Muhammad Faran Khalid, Sonya Cui, Melanie C. Zhang, Renata Husnudinov,Jasmine Mah, Wryan Helmczi, Johnny Su, Brent Guy, Ciaran Scallan, Aaron Jones, Dena Zeraatkar

Published in Pulmonary Pharmacology & Therapeutics in June 2022

Abstract

Background
Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence-based drug therapies that reduce mortality.

Objective
We aimed to perform a systematic review and meta-analysis to assess whether sildenafil reduces mortality, disease progression and adverse side effects.

Methods
We reviewed randomised controlled studies (RCTs) from MEDLINE, Cochrane registry of clinical trials, and EMBASE. Our outcomes of interest included mortality, change in FVC, acute exacerbations and hospitalisations and adverse drug effects leading to discontinuation. We used an inverse variance fixed effects meta-analysis method to calculate pooled relative risk (RR) and mean difference (MD).

Results
A total of 4 studies were included in the systematic review. Sildenafil probably reduces mortality when compared to placebo or to standard care, [RR 0.73 (95% CI 0.51 to 1.04); moderate certainty]. Pooled estimates showed sildenafil may not alter the rate of change of FVC [MD 0.61% (95% CI -0.29 to 1.52)], or DLCO [MD 0.97% (95% CI 0.04 to 1.90)] (both low certainty). Pooled estimated showed sildenafil may not reduce the number of hospitalisations or acute exacerbations, [RR 1.10 (95% CI 0.61 to 1.98); low certainty]. There is probably no difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [RR 0.79 (95% CI 0.56, 1.10); moderate certainty].

Conclusion
Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done to confirm the magnitude and reliability of the point estimate.

 

Medscape article – Does Viagra Reduce Mortality in Pulmonary Fibrosis? (Open access)

 

Pulmonary Pharmacology & Therapeutics article – Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis

 

See more from MedicalBrief archives:

 

Viagra as a candidate drug for Alzheimerʼs disease — US prescription analysis

 

Cystic fibrosis patients may receive insufficient antibiotics to fight lung infections

 

Pfizer is looking for another ‘Viagra’

 

Up to half of men under 50 suffer from erectile dysfunction

 

 

 

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