The Association of Renin-Angiotensin System Blockades and Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Acute Respiratory Failure: A Retrospective Cohort Study

Abstract

Background Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication. Methods We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups. Results A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29–0.86, p = 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22–0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups. Conclusion This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF.

Could patients with chronic obstructive pulmonary disease benefit from renin angiotensin system inhibitors? A meta-analysis

“…We obtained 837 publications in total after the initial research, and then removed 573 duplicates. After screening abstracts and texts of the remaining articles, 20 studies 8–11 19–34 were finally included in the present meta-analysis. The flowchart shows the whole process of study selection ( figure 1 ).…”

“…The characteristics of eligible studies are displayed in table 1 and online supplemental table 2 . Twelve studies 9–11 19 20 22–24 26 28 29 32 were conducted in Europe and North America, and eight studies 8 21 25 27 30 31 33 34 were conducted in Asia. These studies were published between 2006 and 2022.…”

“…The sample size of included studies ranged from 107 to 275 436. Nine studies 8 19 21 24 25 28 30 31 34 included subjects with COPD and other diseases (eg, heart failure (HF), asthma and PH).…”

“…A total of 17 studies 8–10 19–22 24–33 contributed to the primary analysis, which indicated that use of RAS inhibitor decreased the mortality in patients with COPD (RR: 0.69, 95% CI: 0.61 to 0.78, I 2 =99.7%; figure 2 ). Sensitivity analysis suggested that the results were reliable ( online supplemental figure 1 ).…”

“…(1) In six studies, 10 19 21 24 25 30 the included subjects were COPD patients with HF, PH or high cardiovascular risk. No matter in the studies including COPD patients with these comorbidities or in those including subjects without these comorbidities, RAS inhibitor use decreased the mortality of COPD (RR: 0.67, 95% CI: 0.59 to 0.77 and RR: 0.73, 95% CI: 0.60 to 0.89, respectively; online supplemental figure 2 ); (2) Three studies 27 28 32 were regarded as poor quality and fourteen studies 8–10 19–22 24–26 29–31 33 were regarded as high quality, judged by the NOS assessment. In the pooled analysis of high-quality studies, we found a decreased risk of death in patients with COPD who were prescribed RAS inhibitors (RR: 0.69, 95% CI: 0.61 to 0.78; Online supplemental figure 3 ).…”