Time-Dependent Analysis of Calcium Channel Blocker Usage and Risk of Interstitial Lung Disease/Idiopathic Pulmonary Fibrosis: A Nationwide Cohort Study

<bold>Background:</bold> Ca2+ signaling in fibroblasts is one of the important mediators of lung fibrosis. <bold>Aims and objectives:</bold> This study investigated the association between the use of calcium channel blockers (CCB) and the risk of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF). <bold>Methods:</bold> This study was conducted based on Korean National Health Insurance Service-Health Screening Cohort. The enrolled participants were followed up from January 1, 2004 to December 31, 2015, using the International Classification of Diseases, 10th Revision diagnosis codes of ILD (J84.1) and IPF (J84.1A). Cox regression models were employed, incorporating time-dependent variables for CCB medication status, categorized as never-users, <182.5, 182.5–365.0, 365.0–547.5, and ⩾547.5, based on cumulative defined daily dose (cDDD) assessed every 2 years. <bold>Results:</bold> Individuals using CCB medication have a significantly lower risk of ILD and IPF compared to non-users. The adjusted hazard ratios (aHRs) are 0.68 (95% confidence interval (CI) 0.55-0.83) for ILD and 0.69 (95% CI 0.54-0.88) for IPF. Increasing categories of CCB usage were significantly associated with a lower risk of ILD [(aHR 1.23, 95% CI 0.97-1.56), 1.20 (0.85-1.71), 0.49 (0.30-0.81), and 0.27 (0.19-0.39)] and IPF [(aHR 1.21, 95% CI 0.89-1.64), 1.45 (0.96-2.20), 0.83 (0.52-1.33), and 0.25 (1.16-0.38)], compared to never-users. <bold>Conclusion:</bold> This population-based cohort analysis found that individuals using CCBs had a significantly lower risk of ILD and IPF compared to never-users. Furthermore, CCBs were independently associated with a decreased risk of ILD and IPF in a dose–response manner.