Is ACE Inhibitor the Best First-Line Agent for Diabetes With Hypertension?

Was “after the fact” subanalysis designed with enough power to see the proposed difference? The subanalysis of 572 patients compared with the 10,985 patients in the Captopril Prevention Project (CAPPP) might not seem as robust as the original study. Even in the original powered-analysis study, the treatment regimens did not differ in terms of prevention of the primary end point (fatal cardiovascular events; stroke, fatal and nonfatal; myocardial infarction, fatal and nonfatal; all fatal events; all cardiac events; and diabetes). Even the risk of stroke was lower with conventional therapy than with captopril therapy.

The CAPPP claims that captopril has a positive effect in insulin sensitivity, although this claim is not supported by other studies, including double-blinded and placebo-controlled studies.

“Conventional antihypertensive” treatment was defined as “diuretics and/or β-blocker.” Were β-blockers or diuretics administered first, and then were second agents added? Or vice versa? Even in the captopril group, patients received a diuretic if their blood pressure was not under control. The calcium antagonist also was allowed to be added to both treatment groups. The study results did not report the finalized treatment combinations.

The U.K. Prospective Diabetes Study also compared antihypertensive treatment with an ACE inhibitor to that with a β-blocker. Neither drug was superior to the other in any outcome measured, including diabetes-related deaths, myocardial infarction, and all microvascular end points.

I recognize that diabetes, being a comorbidity disease, may require three or more drugs to achieve the specified target levels of blood pressure control. The established practice of choosing an ACE inhibitor as one of the first-line agents in most patients with diabetes is reasonable. And, for patients with microalbuminemia or clinical nephropathy, both ACE inhibitors and angiotensin receptor blockers should be used for the prevention and progression of nephropathy. We should still remember that diuretic- and β-blocker–based therapies also are supported by evidence from other studies of diabetic individuals with hypertension.