Supplementary Material for: Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis

<b><i>Background:</i></b> Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. <b><i>Objectives:</i></b> We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. <b><i>Methods:</i></b> Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. <b><i>Results:</i></b> At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were –78.9 and –187.6 mL/year in patients who received statins at baseline, and –127.9 and –237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (<i>p</i> = 0.9590). <b><i>Conclusions:</i></b> In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF.

**背景**：特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）患者常合并心血管疾病，且诸多IPF患者会接受他汀类药物（statin）治疗以降低心血管风险。**目标**：本研究旨在探讨INPULSIS®临床试验中，基线时使用他汀类药物是否与安慰剂治疗患者的疾病进展差异相关，或是会影响尼达尼布（nintedanib）的治疗效果。**方法**：利用INPULSIS®临床试验的合并数据，对基线时使用与未使用他汀类药物的患者开展事后亚组分析。**结果**：基线时，312例患者使用他汀类药物，749例未使用。在基线使用他汀类药物的患者中，尼达尼布组与安慰剂组患者的用力肺活量（forced vital capacity, FVC）年下降率分别为-78.9 mL/年与-187.6 mL/年；在未使用他汀类药物的患者中，两组年下降率分别为-127.9 mL/年与-237.9 mL/年。尼达尼布的治疗效应在各亚组间保持一致（p=0.9590）。**结论**：在INPULSIS®临床试验中，基线使用他汀类药物的IPF患者经安慰剂治疗后，其FVC下降幅度在数值上低于未使用他汀类药物的患者。基线时使用他汀类药物并不会影响尼达尼布的治疗效果。未来仍需前瞻性数据以评估他汀类药物对IPF病程的影响。