Chicago, IL - A post hoc analysis of data from the African American Study of Kidney Disease and Hypertension (AASK) shows that treatment with the ACE inhibitor ramipril is associated with a significantly lower risk of diabetes among African American study subjects with hypertensive kidney disease than treatment with either the calcium-channel blocker amlodipine or the beta blocker metoprolol [1].

Fasting blood glucose tended to increase over time in this population, lead author Dr Denyse Thornley-Brown (University of Alabama at Birmingham) told heartwire. "We found that ramipril slowed the rate of that rise in blood glucose and led to a reduction in the incidence of diabetes and impaired fasting glucose."

The study is published in the April 10, 2006 issue of the Archives of Internal Medicine.

AASK is a randomized trial that examined three treatments—metoprolol, amlodipine, and ramipril—as initial therapy in 1094 African Americans with hypertensive renal disease [2]. To be included, patients had to have a glomerular filtration rate (GFR) of between 20 and 65 mL/min per 1.73 m², measured by iothalamate clearance, and had to be free of diabetes at baseline. Patients were also randomized in a factorial design to a higher and lower blood-pressure (BP) goal.

The main findings of AASK showed that there did not appear to be an additional benefit of a lower BP goal in slowing the progression of hypertensive nephrosclerosis, the AASK researchers reported. However, the ACE inhibitor was more effective than either the calcium-channel blocker or the beta blocker in slowing GFR decline.

"A lot of the patients we saw in AASK and a lot of the patients I see in clinic are obese, don't exercise, and have a lot of cardiovascular risk factors and risk factors for diabetes," Thornley-Brown said. "The thought was, given that we have three different randomized drug groups (in AASK), would any of these drugs affect the development of new-onset diabetes."

This post hoc analysis assessed two outcomes: diabetes mellitus (DM), defined as first occurrence of at least one follow-up fasting-serum-glucose (FSG) level of at least 126 mg/dL or a clinical diagnosis of diabetes by the local center; and a composite outcome of impaired fasting glucose (IFG), defined as the first occurrence of at least one follow-up FSG level of at least 100 mg/dL or a clinical diagnosis of DM (IFG/DM).

Of the 1017 who had a baseline FSG available or who did not already have IFG at baseline, 147 (14.5%) developed DM and 333 of 776 participants (42.9%) developed the composite end point of IFG/DM. Compared with the other treatments, ramipril therapy was associated with a lower risk of both end points.

The relative risks for these end points with amlodipine vs metoprolol were not statistically significant, the researchers note; for DM, the relative risk was 1.07 (p=0.76), and for IFG/DM, the relative risk was 0.84 (p=0.26).

"Historically, it's been shown that ACE inhibitors or ARBs [angiotensin receptor blockers] reduce the incidence of diabetes, but none of these studies was race-based," Thornley-Brown said. "Those of us who went to medical school before a certain time were told that black patients do not respond well to ACE inhibitors, especially in terms of their high blood pressure, and some studies suggest that in heart failure they didn't respond as well as whites. But the primary results of the AASK study, as well as this study, show benefits to black patients with this group of drugs."

However, she noted, the long-term clinical significance of this observation is unclear; that is, "it's unclear whether the risk associated with the increase in blood glucose seen with the other two groups of drugs, the beta blocker and the calcium-channel blocker, is equivalent to the risk you would see with someone with an adverse lifestyle—someone who's not exercising, etc," she noted. "Preliminary studies suggest that maybe this finding, which we and others have shown, would not have a long-term effect on cardiovascular outcomes."