An extensive meta-analysis calls into question the standard practice of switching from an ACEI to an ARB in patients with type 2 diabetes.
For years, interruption of the renin-angiotensin-aldosterone system (RAAS) pathway through administration of angiotensin-converting enzyme inhibitors (ACEIs) or, if ACEIs can’t be tolerated, by angiotensin receptor blockers (ARBs), has been standard practice. However, a recent study published in JAMA Internal Medicine, may call this practice into question in patients with type 2 diabetes mellitus (T2DM).
In this meta-analysis, a systematic search of Medline, Embase, the Cochrane Central Register, conference proceedings, and article reference lists yielded 35 trials. Trials were excluded if they were crossover studies or if the follow-up period was fewer than 12 months. Twenty-three trials compared ACEIs with placebo or active drug (N=32,827) and 13 compared ARBs with control (N=23,867).
In participants with T2DM, ACEIs significantly reduced the primary end points of all-cause mortality by 13% and cardiovascular (CV) deaths by 17% and the secondary end points of major CV events by 14%, myocardial infarction by 21%, and heart failure (HF) by 19%. In contrast, ARBs did not significantly reduce any of the primary or secondary end points, except HF (RR = 0.70).
This very large meta-analysis provides important information about the differential effects of ACEI vs ARB therapy in T2DM patients. Its limitations include differences in the baseline characteristics of the ACEI and ARB diabetic populations as well as differences in comparator therapies in each of the studies in the meta-analysis. There was also some heterogeneity in the outcomes with different ARBs.
In the absence of a formal head-to-head randomized controlled trial that would validate these results, the findings are nonetheless compelling and suggest that ACEIs, if tolerated, should be the first-line therapy for RAAS pathway blockade in T2DM patients. The optimal medication for ACEI-intolerant patients remains to be determined, but primary care physicians ought to be aware that ARBs do not seem to provide the same risk reduction as ACEIs and so in patients with T2DM should not be considered equivalent to ACEIs.
Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. Published online March 31, 2014. doi:10.1001/jamainternmed.2014.348.