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Cardiovascular (CV) disease is the leading cause of morbidity and mortality in diabetics, and diabetics are at a 2-4 times higher risk of CV disease compared to non-diabetics.1,2  Many trials have found that ACE-inhibitor therapy reduces CV mortality and all-cause mortality, as well as prevents nephropathy in diabetic patients.2.3 However, ARB therapy has not shown the same persistent cardioprotective effects as ACE-inhibitors.1-3 The American Diabetes Association (ADA) recommends that diabetics with hypertension be treated with therapy including an ACE-inhibitor or ARB. The drug classes are considered interchangeable if one cannot be used.1  The two drug classes do not have the same mechanism of action on the renin-angiotensin-aldosterone system (RAAS), and therefore a difference in the benefit in diabetic patients is plausible.  Only one head-to-head trial evaluating renal outcomes, the DETAIL study, compared the ACE-inhibitor, enalapril, to the ARB, telmisartan with a finding of non-inferiority in renal protection, however there was higher CV events (no statistical analysis) with telmisartan.4

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Cheng and colleagues undertook a meta-analysis to evaluate the effects of ACE-inhibitors and ARBs on all-cause mortality, CV deaths, and major CV events in patients with diabetes. They defined major CV events as the composite of CV death, nonfatal MI, stroke, heart failure, and revascularization. Randomized clinical trials that compared ACE-inhibitor or ARB therapy with the defined outcomes that were at least 12 months in duration were included.  Citations were identified using defined MESH terms and reviewing MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, conference proceedings, and article reference lists. Two of the investigators independently reviewed the 436 citations to find 35 trials (or 56,444 patients) that met the defined criteria for the meta-analysis.  Twenty-three of the trials (32,827 patients) involved ACE-inhibitor therapy and 13 trials (23,867 patients) involved ARB therapy compared to either placebo or an active comparator. Active comparators included calcium channel blockers, diuretics, and beta-blockers, as well as one study compared ACE-inhibitor to ARB therapy.2

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The meta-analysis found that ACE-inhibitor therapy in diabetics was associated with a significant decrease in all-cause mortality (RR 0.87; 95% CI 0.78-0.98), CV deaths (RR 0.83; 95% CI 0.70-0.99), major CV events (RR 0.86; 95% CI 0.77-0.95), nonfatal MI (RR 0.79; 95% CI 0.65-0.95), and heart failure (RR 0.81; 95% CI 0.71-0.93).  Conversely, ARB therapy did not significantly decrease any of the outcomes except for heart failure (RR 0.70; 95% CI 0.59-0.82).  Neither therapy was shown to result in a reduced risk of stroke.  The outcomes for the end-points were similar for trials that compared ACE-inhibitor or ARB therapy to placebo or active comparators.  Heterogeneity was found for ARB therapy and CV deaths and was attributed to the two negative olmesartan studies; when the studies were excluded there was no longer a significant finding for heterogeneity.  The mega-regression analysis determined that ACE-inhibitors’ effect on all-cause mortality and CV death was independent of age, baseline blood pressure, presence of ...

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