Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Objective

To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).

Methods

PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.

Results

Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, −0.54 [95% CI, −0.88 to −0.21]; P=.002; I²=96%), IL-6 (WMD, −0.84 [95% CI, −1.03 to −0.64]; P<.001; I²=0%), and TNF-α (WMD, −12.75 [95% CI, −17.20 to −8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, −1.34 [95% CI, −2.65 to −0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, −1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, −0.75 [95% CI, −1.17 to −0.33]; P<.001; I²=96%).

Conclusion

Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.