GEMINI: Carvedilol Reduces Microalbuminuria in Patients with Hypertension and Type 2 Diabetes

Internal Medicine World ReportJuly 2005

GEMINI: Carvedilol Reduces Microalbuminuria in Patients with

Hypertension and Type 2 Diabetes

SAN FRANCISCO—In a head-to-head comparison of beta-blockers in patients with hypertension and type 2 diabetes, carvedilol (Coreg) significantly reduced the development of microalbuminuria compared with metoprolol (Lopressor), reported George L. Bakris, MD, director of the

Hypertension/Clinical Research Center, Rush University Medical Center, Chicago,

at the 20th American Society of Hypertension annual meeting. The finding comes from a study known as GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison

in Hypertensives), a double-blind, multicenter study of 1235 patients with stage 1 or 2 hypertension and well-controlled type 2 diabetes who were being treated with either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to carvedilol, 6.25 to 25 mg twice daily, or metoprolol, 50 to 200 mg twice

daily, in an effort to achieve a trough systolic blood pressure (SBP) ≤135 mm Hg if

baseline SBP was ≥140 mm Hg, or ≤130 if baseline SBP was 130 to 140 mm Hg, and

a trough diastolic blood pressure (DBP) ≤85 mm Hg if baseline DBP was ≥90 mm

Hg, or ≤80 mm Hg if baseline DBP was 80 to 90 mm Hg. Hydrochlorothiazide

(HydroDIURIL) and a dihydropyridine calcium antagonist could be added if needed

to achieve blood pressure (BP) control. At last year’s American Heart Association

annual meeting, Dr Bakris reported that in contrast to metoprolol, carvedilol

was found to have a neutral effect on glycemic control, which was the primary

end point of the study. A total of 930 patients in the study were considered evaluable for albumin:creatinine ratio. At month 5, carvedilol was associated with a 14% relative reduction from

baseline in the albumin:creatinine ratio, whereas metoprolol was associated with a

2.5% increase (P = .003). In patients who were normoalbuminuric at baseline, 6.6% of the carvedilol group progressed to microalbuminuria at 5 months compared with 11.1% of the metoprolol group (P = .03). Microalbuminuria is a modifiable risk marker for cardiovascular disease. According to Dr Bakris, “prevention of its development may translate into additional

cardiovascular risk reduction, an observation yet to be confirmed by clinical trials.” He

added that microalbuminuria is an important variable to consider when selecting antihypertensive

medications because its reduction has been shown in clinical trials to be associated with a relative reduction in the incidence of cardiovascular events compared with no reduction in microalbuminuria. In another analysis of GEMINI, the addition of either of the beta-blockers to

ACE inhibitor or ARB therapy was effective in achieving BP control, said Jackson

T. Wright, Jr, MD, PhD, of Case Western Reserve University, Cleveland, Ohio.

The target BP was attained in nearly 50% of the patients who were given either

carvedilol or metoprolol, mostly at low or medium doses, in addition to their ACE

inhibitor or ARB. With adjunctive therapy (diuretic and/or calcium antagonist), 68%

of patients assigned to carvedilol and 67% of those assigned to metoprolol achieved a

BP <130/80 mm Hg, the goal set for patients with diabetes, said Dr Wright.

In about 40% of the patients who did not achieve a BP <130/80 mm Hg, the

beta-blocker was not titrated to the maximal dose. The addition of a diuretic was

required in almost half of the patients to achieve goal BP, he added.

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