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Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitor in Combination with Angiotensin-Receptor Blocker in Chronic Kidney Disease Based on Dose: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: The purpose of this meta-analysis was to evaluate the controversy of angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) in the treatment of chronic kidney disease (CKD) based on dose. Methods: PubMed, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) from inception to March 2020. The random effects model was used to calculate the effect sizes. Potential sources of heterogeneity were detected using sensitivity analysis and meta-regression. Results: This meta-analysis of 53 RCTs with 6,375 patients demonstrated that in patients with CKD, ACEI in combination with ARB was superior to low-dose ACEI or ARB in reducing urine albumin excretion (SMD, -0.43; 95% CI, -0.67 to -0.19; p = 0.001), urine protein excretion (SMD, -0.22; 95% CI, -0.33 to -0.11; p < 0.001), and blood pressure (BP), including systolic BP (WMD, -2.89; 95% CI, -3.88 to -1.89; p < 0.001) and diastolic BP (WMD, -3.02; 95% CI, -4.46 to -1.58; p < 0.001). However, it was associated with decreased glomerular filtration rate (GFR) (SMD, -0.13; 95% CI, -0.24 to -0.02; p = 0.02) and increased rates of hyperkalemia (RR, 2.07; 95% CI, 1.55 to 2.76; p < 0.001) and hypotension (RR, 2.19; 95% CI, 1.35 to 3.54; p = 0.001). ACEI in combination with ARB was more effective than high-dose ACEI or ARB in reducing urine albumin excretion (SMD, -0.84; 95% CI, -1.26 to -0.43; p < 0.001) and urine protein excretion (SMD, -0.24; 95% CI, -0.39 to -0.09; p = 0.002), without decrease in GFR (SMD, 0.02; 95% CI, -0.12 to 0.15; p = 0.78) and increase in rate of hyperkalemia (RR, 0.94; 95% CI, 0.65 to 1.37; p = 0.76). Nonetheless, the combination did not decrease the BP and increased the rate of hypotension (RR, 3.95; 95% CI, 1.13 to 13.84; p = 0.03) compared with high-dose ACEI or ARB. Conclusion: ACEI in combination with ARB is superior in reducing urine albumin excretion and urine protein excretion. The combination is more effective than high-dose ACEI or ARB without decreasing GFR and increasing the incidence of hyperkalemia. Despite the risk of hypotension, ACEI in combination with ARB is a better choice for CKD patients who need to increase the dose of ACEI or ARB (PROSPERO CRD42020179398).

SUBMITTER: Zhao M

PROVIDER: S-EPMC8134749 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePatients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown.ObjectiveTo evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI.Design, setting, and participantsThis retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years.ExposuresUse of an ACEI or ARB within 6 months after hospital discharge.Main outcomes and measuresThe primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge.ResultsThe study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD.Conclusions and relevanceAmong patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.

Dataset Information

Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitor in Combination with Angiotensin-Receptor Blocker in Chronic Kidney Disease Based on Dose: A Systematic Review and Meta-Analysis.

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