AACE 2011: Treating Insulin Resistance in Hypertension and Chronic Kidney Disease

George Bakris, MD, discusses combination therapies for treating hypertension, chronic kidney disease, and diabetes.

The global burden of hypertension is growing, with a predicted 60% increase in the adult population between the years 2000 and 2025, said George Bakris, MD, at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists. Speaking at one of the “hot topics” sessions, Bakris is professor of Medicine at the University of Chicago School of Medicine in Illinois, and serves as director of the Hypertension Center in the Diabetes Institute. Bakris’s talk focused on combination therapies for treating hypertension, chronic kidney disease, and diabetes.

Of the many cardiovascular risk factors are hypertension, smoking, obesity, physical inactivity, dyslipidemia, diabetes, microalbuminuria, and estimated glomerular filtration rate. With the interrelationship between various systems, one question is what is the initial therapy in kidney disease or diabetes that best reduces cardiovascular risk? Combination therapy is here to stay, explained Bakris, and is needed to achieve target blood pressure. This method of treatment has spilled over from hypertension and is also used for glucose and lipid control. He cited the STAR (Study of Trandolapril/Verapamil SR And Insulin Resistance) study that aimed to determine whether impaired glucose tolerance (IGT) improved with combination ACC versus a diuretic combination in patients with metabolic syndrome. These patients did not have diabetes based on fasting blood glucose. Primary outcome was change from baseline in a two-hour glucose tolerance test. Starting at 12 weeks, insulin resistance actually got worse on the diuretic compared to ACC, and this continued through the end of the study. In addition, mean A1c increased from baseline in patients receiving the diuretic combination, and the percentage of patients that developed an A1c >7% at study end was significantly higher than those receiving the ACC combination. The authors concluded that in patients with IGT, normal kidney function, and hypertension, combination ACC reduces risk of new-onset diabetes compared to a diuretic combination.

As an aside to his discussions of combination therapy, Bakris described some of the confusion associated with microalbuminuria. “Microalbuminuria is dead,” he said. “It should not be used as an endpoint, and the FDA does not even accept it.” In 1989, researchers biopsied diabetics and concluded that microalbuminuria was the earliest clinical correlate. Fast-forward several years to another study that found four patterns of microalbuminuria, demonstrating that it is not a reliable marker for identifying kidney disease.

Finally, he described the ACCOMPLISH (Avoiding Cardiovascular Events through COMbination Therapy in Patients Living with Systolic Hypertension) study, which was designed to determine whether high-dose fixed combination of benazepril-amlodipine would be more effective than benazepril-hydrochlorothiazide in reducing cardiovascular morbidity and mortality. In a diabetes sub-group study, the goal was to compare cardiovascular endpoints in diabetic patients at very high risk (eg, previous myocardial infarction or stroke), diabetes patients not at high risk, and patients without diabetes. Results found an advantage of the benazepril-amlodipine combination, but the overall benefit was not driven by those with diabetes, explained Bakris.

Lending support to research findings, Bakris cited The American Society of Hypertension’s recommendation to use fixed-dose antihypertensive combinations such as ACE inhibitor/diuretic, ARB/diuretic, ACE inhibitor/CCB, or ARB/CCB. “We need to use common sense and be aggressive with lifestyle interventions,” asserted Bakris, “and if we combine that with medications, we’ll be good.”