Can RAS inhibitors reduce mortality among patients with COPD?

In their study published in BMJ Open Respiratory Research, the investigators stated that the evidence is weak due to potential biases from retrospective studies and the heterogeneity across included studies.

Chronic obstructive pulmonary disease is a multisystemic disorder that is considered to be related to chronic systemic inflammation. RAS (renin-angiotensin system) inhibitor exerts anti-inflammatory action in many systems and has been shown relevant to COPD's pathogenesis. RAS inhibitors include angiotensin receptor blockers (ARB) and ACE inhibitors (ACEI). However, there is a controversy on the association between using RAS inhibitors and the prognosis of COPD patients.

Therefore, Yong Xu, Nanjing University of Chinese Medicine, Nanjing, China, and colleagues conducted a meta-analysis and systematic review to summarise current evidence.

For this purpose, the researchers searched the online databases for eligible studies by the end of 30 September 2022. They selected randomised controlled trials (RCTs) or observational studies investigating the association of RAS inhibitor use with COPD prognosis (risk of acute exacerbation or mortality).

Quality assessment of observational studies was done using the Newcastle-Ottawa Scale, while the Cochrane risk-of-bias tool assessed RCTs' quality. Relative risk (RR) was the effect measure. The funnel plot implied significant publication bias. The meta-analysis included a total of 20 studies with 5 51 649 subjects.

The authors reported the following findings:

• The overall analysis indicated that RAS inhibitor use decreased the risk of death in patients with COPD (RR: 0.69).
• Subgroup analyses were conducted according to comorbidities, race and type of RAS inhibitors, and the results kept consistent.
• In the pooled analysis of prospective studies, RAS inhibitor use did not significantly decrease the mortality (RR: 0.89).
• Additionally, the risk of exacerbations of COPD did not decrease in patients prescribed RAS inhibitors (RR: 0.99). The funnel plot indicated significant publication bias.

The findings from the meta-analysis suggest that RAS inhibitors were associated with a mortality reduction in COPD patients. However, the evidence supporting the positive association needed to be stronger.

"Considering the proven benefits of RAS inhibitors in CVD, routine administration of RAS inhibitors in COPD with these comorbidities seems acceptable," the researchers wrote. "In addition, whether RAS inhibitors could reduce COPD-related mortality still need further demonstration in high-quality epidemiological studies or RCTs."

RAS inhibitors seem to reduce mortality in COPD patients, but the evidence supporting this positive association is not strong.

Reference:

Lv H, Huang J, Miao M, et alCould patients with chronic obstructive pulmonary disease benefit from renin angiotensin system inhibitors? A meta-analysisBMJ Open Respiratory Research 2023;10:e001569. doi: 10.1136/bmjresp-2022-001569.