Does losartan benefit patients with Interstitial Lung Disease (ILD)?

Losartan Does Not Have Established Benefit for ILD and Is Not Recommended in Current Guidelines

Losartan is not recommended as a treatment for interstitial lung disease based on current clinical practice guidelines, which do not include it among approved therapeutic options for any form of ILD. The available evidence consists only of preliminary preclinical and small pilot study data that are insufficient to support its clinical use.

Guideline-Based Treatment Recommendations

Current evidence-based guidelines for ILD management do not include losartan as a treatment option:

For Idiopathic Pulmonary Fibrosis (IPF)

• Antifibrotic therapy with nintedanib or pirfenidone is the established first-line treatment, slowing annual FVC decline by approximately 44-57% 1
• These agents are the only FDA-approved medications proven to slow disease progression in IPF 1, 2

For Connective Tissue Disease-Associated ILD (CTD-ILD)

• Mycophenolate is the preferred first-line immunosuppressive therapy across all SARD-ILD subtypes 3, 4
• Alternative options include rituximab, cyclophosphamide, and azathioprine (except in systemic sclerosis) 3, 4
• For systemic sclerosis-ILD specifically, nintedanib is conditionally recommended as an additional first-line option 3

For Progressive Pulmonary Fibrosis

• Nintedanib is approved for chronic fibrosing ILD with a progressive phenotype, regardless of underlying etiology 2
• This includes patients with chronic hypersensitivity pneumonitis, idiopathic NSIP, unclassifiable ILD, autoimmune ILD, and sarcoidosis 2

Limited Evidence for Losartan

The only clinical data on losartan in ILD comes from a single small pilot study:

• A 2012 pilot trial enrolled 20 patients with IPF (17 evaluable) treated with losartan 50 mg daily for 12 months 5
• Results showed 12 of 17 patients had stable or improved FVC at 12 months, with similar findings in secondary endpoints 5
• This was an uncontrolled, single-arm pilot study without a placebo comparison group, representing very low-quality evidence 5
• No subsequent randomized controlled trials have been conducted to validate these preliminary findings

Preclinical Rationale

• Animal studies showed losartan reduced bleomycin-induced lung fibrosis in rats, potentially through increased prostaglandin E2 synthesis and COX-2 expression 6
• However, preclinical findings frequently fail to translate to human efficacy in ILD

Clinical Implications

Given the absence of losartan from evidence-based guidelines and the availability of proven effective therapies, losartan should not be used for ILD treatment outside of clinical trials. The following approach is recommended:

For Newly Diagnosed ILD

• Establish the specific ILD subtype through multidisciplinary evaluation including HRCT, PFTs, and serologic testing 7, 4
• For IPF: initiate nintedanib or pirfenidone 1
• For CTD-ILD: initiate mycophenolate or alternative immunosuppressive therapy 3, 4
• For progressive fibrosing ILD of other etiologies: consider nintedanib 2

Monitoring for Treatment Response

• Perform PFTs every 3-6 months for moderate-to-severe or progressive disease 7
• Repeat HRCT within 6-12 months to assess radiological progression 7
• Monitor for progressive pulmonary fibrosis phenotype (≥10% FVC decline, worsening symptoms, or radiographic progression) 4

Important Caveats

• Do not delay proven antifibrotic or immunosuppressive therapy to trial unproven agents like losartan
• The 2012 pilot study's lack of a control group makes it impossible to determine whether observed stability was due to losartan or natural disease variability 5
• Patients with ILD and comorbid hypertension may receive losartan for blood pressure management, but this should not be considered ILD-directed therapy