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ACEIs Standard for Blacks With Renal Insufficiency

Results of a landmark trial of 1,000. An angiotensin-converting enzyme inhibitor should be the cornerstone of treatment for African Americans with hypertension and impaired renal function, based on the results of a landmark trial with more than 1,000 patients.

Many physicians have favored using a calcium channel blocker over an angiotensin-converting enzyme inhibitor (ACEI) for African Americans with hypertension because, in general, the blood pressure of blacks falls more dramatically in response to a calcium channel blocker.

But results from the African American Study of Kidney Disease and Hypertension (AASK) showed that “it’s not just lowering blood pressure that’s important” for patients with renal insufficiency, Dr. George L. Bakris said at the annual meeting of the American Society of Nephrology.

The results of AASK, like those of many other recently completed studies, show that drugs that block the renin-angiotensin system pack an extra punch for kidney protection.

“African Americans with hypertension and a urine protein to creatinine ratio of more than 0.22, left ventricular hypertrophy, or diabetes should be first treated with an ACE inhibitor,” said Dr. Robert G. Luke, director of internal medicine at the University of Cincinnati and a coinvestigator in AASK. First-line treatment with an ACEI also is probably best for African Americans with hypertension and microalbuminuria, added Dr. Luke, noting that the AASK results did not prove this. For African Americans with hypertension who don’t fall into one of these higher-risk groups, treatment should follow the existing guidelines of the sixth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, he added.

Although the AASK results put ACEIs first for patients with impaired renal function, physicians should not worry that calcium channel blockers are bad for these patients. “It’s also critical to get blood pressure under control. It often takes three or four drugs to do this, and physicians shouldn’t retreat from using a calcium channel blocker,” explained Dr. Bakris, a professor of medicine at Rush-Presbyterian–St. Lukes Medical Center, Chicago, and another AASK coinvestigator.

The study enrolled 1,094 African Americans with hypertension, a glomerular filtration rate (GFR) of 20-65 mL/min per 1.73 m2, and no other identified cause of renal insufficiency. Enrollment occurred at 21 U.S. centers during 1995-1997, and GFR values were monitored for a median of 3.8 years, until September 2001.

Patients were randomized to two blood pressure targets: The usual target group aimed for a mean arterial pressure of 102-107 mm Hg (corresponding to a systolic and diastolic pressure of about 140/90 mm Hg), and the low target group aimed for a mean arterial pressure target of no more than 92 mm Hg (corresponding to 125/75 mm Hg).

Patients also were randomized to three treatment groups based on the first-line antihypertensive drug: the ACEI ramipril (436 patients); the calcium channel blocker amlodipine (217 patients); or the -blocker metoprolol (441 patients).

Patients who required additional drugs to reach their target pressures had these drugs added in the following order: furosemide, doxazosin, clonidine, and minoxidil. Patients with the usual target pressure needed an average of from 2.5 to 3 drugs to reach their goal; patients with the low target pressure needed an average of from 3 to 3.5 drugs to reach their goal.

The results showed no difference between the two target groups in terms of the impact on the study’s main outcomes: loss of GFR, or a combined clinical end point of death, end-stage renal disease, or a drop in GFR of 50% or at least 25 mL/min per 1.73 m2 from the baseline rate.

But the results showed a difference among the three first-line antihypertensive drugs used. Treatment with amlodipine led to better short-term protection of GFR, but ramipril was superior over the long term, Dr. Bakris said. Ramipril also was superior to metoprolol in preserving GFR at the first follow-up at 6 months and throughout the entire follow-up period.

Ramipril also was substantially better than both of the other drugs for preventing worsening of proteinuria. “The ACE inhibitor was better for slowing declines in kidney function, [which] may mean that fewer patients would need to start dialysis,” Dr. Bakris said.