Objectives

To evaluate the efficacy of losartan, an angiotensin receptor blocker, to reduce emphysema progression in patients with COPD and mild to moderate emphysema.

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease comprising chronic bronchitis and emphysema. COPD is a major cause of morbidity and mortality. Smoking cessation slows the progression of the disease, and bronchodilators can provide sustained improvement in lung function, but there are no pharmacologic agents that clearly modify emphysema progression.

Angiotensin receptor blockers (ARBs) have been suggested as potential drugs to slow the progression of COPD. A few trials have shown that patients treated with ARBs had slower progression of radiographic emphysema. The LEEP study was initiated to test the hypothesis that the ARB losartan would reduce the progression of emphysema in patients with COPD with mild to moderate emphysema.

Participants

Eligible participants were age ≥40 years; had stable moderate to severe COPD, defined by FEV1/FVC ratio ≤0.70 and FEV1 20–80% of predicted; were a current or former smoker with ≥10 pack-years of exposure; and had an inspiratory high-resolution computed tomography (HRCT) scan with mild to moderate emphysema (PCT950, 5–35%).

A total of 220 participants were enrolled. 108 participants were randomized to receive losartan, and 112 participants were randomized to receive the placebo.

Design

LEEP was a randomized, placebo-controlled multicenter trial. Participants were randomly assigned (1:1) to receive losartan or placebo. The dose was 50 mg losartan or placebo given as one capsule daily for 2 weeks, and, if well tolerated and the systolic blood pressure was >90 mm Hg, it was increased to two capsules. Participants and site investigators were masked to treatment assignment.

Participant responses to the St George’s Respiratory Questionnaire, the modified Medical Research Council dyspnea scale, the COPD Assessment Test, and the Physical Function–Short Form 20a were collected. The number and severity of COPD exacerbations were recorded. COPD exacerbations were defined as two or more new or worse symptoms for ≥3 days and classified by treatment as mild (neither antibiotics nor oral steroids), moderate (an antibiotic or oral steroid), or severe (hospitalization).

The primary outcome measure was the change in quantitative whole-lung emphysema score after 48 weeks measured by the percentage of lung voxels less than -950 Hounsfield units (PCT950) on full inspiratory HRCT.

Conclusions

Losartan does not prevent progression of emphysema in patients with COPD who have mild to moderate pulmonary emphysema.

Wise RA, Holbrook JT, Brown RH, et al. Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial [published correction appears in Am J Respir Crit Care Med. 2024 Oct 1;210(7):965. doi: 10.1164/rccm.v210erratum6]. Am J Respir Crit Care Med. 2022;206(7):838-845. doi:10.1164/rccm.202201-0206OC

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