ACEI/ARBs superior to CCBs at albuminuria reduction in nephropathy due to diabetes, hypertension

Renin-angiotensin system inhibitors perform better than calcium channel blockers (CCB) at decreasing albuminuria among diabetic and hypertensive patients with nephropathy, according to the results of a systematic review and meta-analysis.

“Although our findings suggest that [angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-II receptor blockers (ARB)] are statistically more effective than CCB in reducing albuminuria, it should be noted that the net clinical effect is small, as the standardized difference in means (SMD) between both groups was only 0.44 mg/24 h,” the researchers said.

The databases of Medline, Embase, Central, and ClinicalTrials.gov were searched for records comparing CCBs to ACEI/ARB and reporting pre- and postintervention albuminuria measurements. Two reviewers independently screened abstracts for randomized controlled trials in adults.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to select 29 trials from 855 records. Data were synthesized through a random-effects model.

A total of 2,113 trial participants with hypertension and diabetes mellitus who had the equivalent of ≥30 mg/day of urinary albumin excretion provided data for analysis. Inhibitors of the renin-angiotensin system were superior to CCBs at reducing albuminuria (SMD, –0.442, 95 percent confidence interval [CI], –0.660 to –0.225; p<0.001). [Am J Med 2021;134:104-113.E3]

Such finding was independent of the degree of reduction in blood pressure achieved with both agents. In addition, no difference was observed between ACEI/ARB and CCB regarding markers of renal function, as indicated by postintervention estimated glomerular filtration rate and serum creatinine level.

Subgroup analysis revealed a reduction in the degree of albuminuria with CCB therapy as was seen with ACEI/ARB. This small net clinical effect was consistent with the findings of another meta-analysis, which showed that ACEI/ARBs were not superior to other antihypertensives at lowering cardiovascular or renal endpoints in hypertensive, diabetic patients without albuminuria. [BMJ 2016;352:i438]

“Consequently, while these findings support the common practice of favouring ACEI/ARBs in patients with hypertension and diabetes who have albuminuria, they also indicate that CCB may provide a similar clinical benefit, especially in cases with intolerance or a lack of response to ACEI/ARBs,” the researchers said.

The current study was limited by the lack of access to individual patient data and small sample sizes in several trials analysed. Moreover, there was high statistical heterogeneity among the included studies.

“CCBs have been reported to improve urinary albumin excretion when added to an ACEI/ARB in nondiabetic subjects,” the researchers said. [Kidney Blood Press Res 2009;32:51-58; N Engl J Med 2008;359:2417-2428]

“Similarly, a number of studies have suggested that CCBs might be as effective as ACEI/ARB for the management of albuminuria in patients with diabetes and chronic kidney disease,” they added. [Arch Intern Med 1993;153:973-980; Clin Drug Investig 1997;13:42-49; Korean J Intern Med 2017;32:497-504; Blood Press 1993;2:301-308; J Hum Hypertens 1993;7:333-339]