Effects of roflumilast on arterial stiffness in COPD (ELASTIC): A randomized trial.

ABSTRACT

BACKGROUND AND OBJECTIVE: Cardiovascular risk is substantially increased in patients with COPD and can be quantified via arterial stiffness. The PDE-IV inhibitor roflumilast revealed a potential reduction of COPD-related cardiovascular risk. We aimed to investigate the effects of roflumilast on arterial stiffness by quantification of pulse wave velocity (PWV) in stable COPD. METHODS: In this randomized placebo-controlled trial, 80 COPD patients received roflumilast or placebo for 24 weeks. The primary outcome was the change in cf-PWV. Secondary outcomes comprised markers of vascular function (e.g. Aix and RHI), systemic inflammation (e.g. IL-6 and TNF-α) and clinical characteristics of COPD (e.g. CAT and 6MWT). RESULTS: A total of 33 and 34 patients completed the roflumilast and placebo arm, respectively (age, median (IQR) 64.5 (61-69.5) vs 64.5 (56-72) years; FEV1 , median (IQR) 34.5 (25.5-48.6) vs 35.3 (27-46.8) % predicted; 6MWT, median (IQR) 428 (340-558) vs 456 (364-570) m). Change from baseline PWV did not show a significant difference between roflumilast and placebo (+5.0 (95% CI -2.0 to +13.0) vs 0.0 (95% CI -7.0 to +7.0)%, P = 0.268). Roflumilast did not improve markers of vascular function or systemic inflammation. We observed a significant improvement in change from baseline 6MWT with roflumilast versus placebo (+53.0 (95% CI +19.1 to +86.9) vs -0.92 (95% CI -35.1 to +33.3) m, P = 0.026). CONCLUSION: Our study revealed no beneficial effects of roflumilast on arterial stiffness. Further studies are needed to test a potential improvement of exercise capacity with roflumilast in COPD.