IPF: ACE inhibitor use linked to slower progression

Takeaway

• In exploratory analysis of 2 pivotal pirfenidone (Esbriet; Genentech) trials, patients with idiopathic pulmonary fibrosis (IPF) experienced slower disease progression if they used an angiotensin-converting enzyme inhibitor (ACEi) vs using neither an ACEi nor angiotensin II receptor blockers (ARBs).
• Survival was worse with ARBs vs use of neither drug.
• Results are hypothesis-generating; prospective trials needed.

Why this matters

• Fibrosed lung contains abundant angiotensin peptides.
• Preclinical evidence suggests ACEi and ARB slow fibrosis.

Key results

• At baseline:
  • 111 patients used an ACEi;
  • 121 used ARBs; and
  • 392 used neither (non-ACEi/ARB).
• Disease progression (HRs; 95% CIs):
  • ACEi vs non-ACEi/ARB: 0.6 (0.4-0.9; P=.026).
  • ARB vs non-ACEi/ARB: 0.9 (0.6-1.2; P=.413).
• Mortality (HRs; 95% CIs):
  • ACEi vs non-ACEi/ARB: 1.1 (0.5-2.9; P=.782).
  • ARB vs non-ACEi/ARB: 2.5 (1.2-5.2; P=.013).
• Similar trends, though not reaching significance, in pooled analysis with INSPIRE.

Study design

• Post hoc analysis of participants using placebo in CAPACITY and ASCEND (n=624).
• Stratifying by baseline antihypertensive, authors performed multivariate analysis.
• Outcome: composite of disease-progression measures, all-cause mortality at 52 weeks.
• For validation, authors pooled findings with data from INSPIRE.
• Funding: F. Hoffmann-La Roche Ltd.

Limitations

• Post hoc analysis; few events.
• Results might differ if patients were taking antifibrotics.