Statins: cause of fibrosis or the opposite? Effect of cardiovascular drugs in idiopathic pulmonary fibrosis

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with poor prognosis despite the recent availability of two antifibrotic drugs. Patients are more susceptible to cardiovascular comorbidities. In this study, we aimed to determine the impact of concomitant cardiovascular drugs on disease progression and survival in a modern IPF cohort. Methods: The database of a tertiary referral centre for interstitial lung diseases in Belgium was reviewed for statin, antiaggregant, anticoagulant and metformin therapy. For a study period of four years, we noted both FVC % and DLCO% trajectories along with survival as outcome measurements. Results: 323 patients were included of which 45% had at least one cardiovascular comorbidity. 274 (86%) patients received antifibmtic therapy. Statin users (n = 171) displayed significantly slower annual FVC% (difference 2.9%, CI 1.6-4.4, p < 0.001) and DLCO% decline (difference 1.3%, CI 0.24-2.3, p = 0.013). Results for antiaggregant therapy (n = 152) were inconclusive: we found a trend for slower FVC decline (p = 0.098) and a numerically decrease in survival rates (HR 1.63, p = 0.074) in a multivariate Cox analysis. Anticoagulant use (n = 49) showed a trend towards worse DLCO decline (difference -1.3%, CI -2.6 - 0.02, p = 0.055).r Metformin (n = 28) therapy did not affect IPF progression in terms of pulmonary function test evolution or survival. Conclusion: This retrospective study demonstrated a benefit of statin therapy on IPF progression. Our observations emphasize the need for large clinical trials analysing the effect of statins, as well as other cardiovascular drugs, in the management of IPF patients.