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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.

      Abbreviations and Acronyms:

      ACEI (angiotensin-converting enzyme inhibitor), AngII (angiotensin II), ARB (angiotensin receptor blocker), CAD (coronary artery disease), CRP (C-reactive protein), CVD (cardiovascular disease), IL-6 (interleukin 6), RAAS (renin-angiotensin-aldosterone system), RCT (randomized controlled trial), T2DM (type 2 diabetes mellitus), TNF-α (tumor necrosis factor α), WMD (weighted mean difference)
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      Linked Article

      • Making a Case for the Anti-inflammatory Effects of ACE Inhibitors and Angiotensin II Receptor Blockers: Evidence From Randomized Controlled Trials
        Mayo Clinic ProceedingsVol. 97Issue 10
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          In this issue of Mayo Clinic Proceedings, Awad and colleagues1 present a meta-analysis of randomized controlled trials evaluating the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as anti-inflammatory agents. Their findings support the beneficial role of ACEIs and ARBs in reducing blood levels of inflammatory markers but reveal potential differences in their anti-inflammatory effects. However, regardless of the class of medications used, the implications of the results merit the need to better understand the inflammation-alleviating effects of renin-angiotensin-aldosterone system (RAAS) inhibition.
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