Angiotensin Receptor Blockade Treatment for COPD: Phase II Trial

SESSION TITLE: Emerging Therapies in COPD SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 27, 2015 at 02:45 PM - 04:15 PM PURPOSE: Treatments are needed to slow the progression of COPD. In observational studies and animal models, angiotensin receptor blockers (ARBs) have been associated with reduced morbidity, mortality and slowed progression of emphysema. We conducted a phase II randomized double-blind placebo-controlled study to determine the impact of the ARB losartan upon progression of COPD ad CT-defined emphysema. METHODS: Participants were age 40 years or older with mild-to-moderate COPD defined by a ≥ 10 pack-year smoking history, post-bronchodilator FEV1/FVC less than 0.70, FEV1 30-70% predicted, and DLCO ≥ 35% predicted. Participants were assigned to receive losartan 100mg or placebo by mouth daily for 12 months. Chest CTs were performed at baseline, 6 months and 12 months follow-up. We defined emphysema as 5-35% of voxels < -950HU (pct950). Quantitative measures of emphysema and airway wall thickness were measured to assess anatomic lung remodeling. Other measures assessed included spirometry, DLCO, 6MWT, SGRQ and sputum differential cell counts. Clinical and radiographic characteristics were compared using t-tests. RESULTS: 54 were treated with losartan and 52 with placebo. At baseline, 50 participants had CT-defined emphysema. Among those with baseline emphysema, the pct950 decreased (less emphysema) after 12 months of losartan therapy (mean change at 12 months: -0.32%, SD: 3.7) and increased after 12 months of placebo (mean change at 12 months: +2.18%, SD: 4.9); the group difference in these changes in this small sample was not statistically significant (p=0.06). Examined individually, each lobe showed a trend towards progression of emphysema with placebo but not with losartan. There were no significant changes in spirometry, DLCO, and SGRQ in either treatment group. Among those without emphysema at baseline, losartan therapy did not alter any outcome measures. CONCLUSIONS: In this phase 2 trial, losartan may prevent emphysema progression in COPD patients who have CT-defined emphysema. CLINICAL IMPLICATIONS: Based on these data, ARBs have the potential to be of benefit in patients with emphysema and a definitive trial is warranted. DISCLOSURE: The following authors have nothing to disclose: Allison Lambert, Enid Neptune, Robert Brown, Gregory Diette, M. Drummond, Nadia Hansel, Mark Liu, David Shade, Robert Wise Losartan is a medication not approved for the clinical purpose of treating COPD. We will be presenting data about the impact of losartan upon COPD outcomes and CT progression of emphysema in the context of a research study.