A subset of patients with chronic obstructive pulmonary disease (COPD) with emphysema appeared to benefit from treatment with an angiotensin receptor blocker, supporting preclinical evidence of efficacy, a randomized clinical study suggested.
Overall, patients with COPD treated with losartan (Cozaar) had no improvement compared with placebo-treated patients. However, the subset of patients with emphysema at baseline had stabilization of emphysema at 6 months, whereas patients in the placebo group exhibited a 3% rate of progression (P=0.042). Anatomic analysis also showed a significant difference for the left upper lobe in favor of losartan (P=0.049).

At 12 months, the overall trend toward stability persisted in the patients who had emphysema at baseline but was no longer significant. The anatomical analysis showed a consistent pattern of stability with losartan versus progression with placebo, achieving statistical significance in the right middle lobe, Allison Lambert, MD, of Johns Hopkins, reported here at CHEST 2015.
“From these data, we conclude that, among patients with COPD who have CT-defined emphysema, losartan has the potential to prevent emphysema progression,” said Lambert. “Our secondary outcomes were unchanged.
“The next step in our line of clinical investigation will be to conduct a phase III clinical trial, supported by the NIH Pulmonary Trials Consortium. We anticipate recruiting 220 patients with emphysema, which will afford 90% power to detect differences as identified in our phase II trial.”
The emergence of differences between the groups after a relatively brief treatment period was impressive, but the timing of medication administration and CT scans could influenced findings, suggested Jay Peters, MD, of the University of Texas Health Science Center in San Antonio.
“One of my concerns is that [the improvement] was in the left upper lobe early on and then the right middle lobe at 12 months,” said Peters. “How did you control the time of day that the CT was done and how did that correlate with the medications? It would seem that somebody who had just taken medication with air trapping could look quite different.”

Alluding to data showing that the right middle lobe is the most common site of progression with CT-defined emphysema, Lambert responded, “I do think that this finding within the right middle lobe at 12-month follow-up is true and perhaps compelling. What was striking to me at the 12-month follow-up was the trend across all lobes; all the lobes had stopped progressing.”
The rationale for using ARBs in emphysema dates back to preclinical studies of Marfan syndrome. Animals with emphysema-like changes in alveoli were treated with losartan, which partly reversed the changes. Subsequent studies in mice showed that losartan attenuated adverse lung effects of cigarette smoke and restored lung architecture.
Relevant clinical studies include a trial of the ARB irbesartan (Avapro) in patients with COPD, leading to some changes associated with improved lung function and architecture. A retrospective case-control study showed a reduction in COPD hospitalization and mortality among patients treated with statins and ARBs.
In her presentation here, Lambert reported findings from a randomized, proof-of-concept study to determine whether losartan would prove or slow the progression of emphysema in patients with COPD. Patients with mild to moderate COPD were randomized to losartan or placebo and followed for 12 months. Outcomes of interest included CT-assessed percent emphysema and airway wall thickness; spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide; and quality of life/health status.
The final analysis included 106 patients, for whom Lambert reported anatomic and functional outcomes. In the overall population, patients assigned to losartan did no better than those in the placebo group with respect to any of the outcomes at 6 or 12 months. However, a prespecified analysis of patients with CT-confirmed emphysema at baseline (n=46) showed anatomical changes favoring the losartan group.

At 6 months, total-lung emphysema had decreased by 0.78% in the losartan group and increased by 3.03% in the placebo group (P=0.042). The lobe-specific anatomic analysis showed a 0.86% decrease in emphysema in the left upper lobe among patients treated with losartan versus an increase of 2.97% in the placebo group (P=0.049). Other lobe-specific values did not differ significantly between the groups, nor did any of the functional outcomes assessed.
At 12 months, patients in the losartan group still had an overall decrease in emphysema (-0.32%) compared with an increase of 2.18% in the placebo group, but the difference was no longer significant (P=0.064). Emphysema in the right middle lobe had decreased by 0.72% in the losartan group but increased by 3.34% in the placebo group (P=0.019).
All of the other lobe-specific assessments showed stable disease in the losartan arm versus 2% to 3% emphysema progression with placebo, although the differences did not achieve statistical significance. None of the functional outcomes differed significantly between treatment groups.