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RAS inhibitors reduce acute exacerbation risk in COPD

RAS inhibitor use in chronic obstructive pulmonary disease patients appears to reduce the risk of acute exacerbations and mortality

In a propensity-matched study, Danish researchers found that in patients with chronic obstructive pulmonary disease (COPD) prescribed drugs affecting the renin-angiotensin-system (RAS inhibitors), there was a lower risk of both acute exacerbations and death.

COPD remains a major public health problem with one analysis finding that globally in 2019, there were 212.3 million cases and which accounted for 3.3 million deaths. COPD is characterised not only by local pulmonary, but also by systemic, inflammation which promotes the development of extra-pulmonary and cardiovascular co-morbidities. Although traditionally used in the management of hypertension, there is emerging evidence that RAS inhibitors such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) also have potential benefits in COPD patients. In fact, evidence from a retrospective analysis suggest that RAS inhibitors have dual cardiopulmonary protective properties, reducing the risk of myocardial infarction as well as COPD-related hospitalisation.

In the current study, the Danish researchers hypothesised that the use of RAS inhibitors could reduce the incidence of acute exacerbations of COPD as well as mortality in those with severe disease. Adopting a propensity-score matching approach, the team matched COPD patients prescribed a RAS drug with a similar cohort of COPD patients given bendroflumethiazide as an active comparator. The primary outcome was severe acute exacerbations of COPD within 12 months after study entry or death in the same period.

RAS inhibitor use and COPD outcomes

A total of 3029 patients with a median age of 72 years (69.1% female) and prescribed either an ACEi or ARB and propensity matched to a similar number prescribed bendroflumethiazide.

The use of either an ACEi or ARB was associated with a 14% lower risk of exacerbations or death compared to those using bendroflumethiazide (hazard ratio, HR = 0.86, 95% CI 0.78 – 0.95). This reduced risk was also evident in a sensitivity analysis of the propensity-score-matched population (HR = 0.89, 95% CI 0.83 – 0.94) and in an adjusted Cox proportional hazards model (HR = 0.93, 95% CI 0.89- 0.98).

The authors concluded that RAS inhibitor treatment lowered the risk of both acute exacerbations and death in those with COPD. However, they added the caveat that while there is a biologically plausible explanation for this finding, randomised controlled trials were needed to confirm this effect, given the observational nature of their study.

Vilstrup F et al. Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study. BMJ Open Respir Res 2023

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