The largest clinical trial ever conducted in African Americans with kidney disease has concluded that an antihypertensive drug in the class of angiotensin-converting enzyme (ACE) inhibitors is superior to two other classes of drugs for slowing kidney disease due to hypertension. The study also found that a very low blood pressure provides no additional benefit for the kidneys than the established standard. Results appear in the Journal of the American Medical Association November 20.
"We were surprised that the lower blood pressure level didn't have more of an effect on the kidney," said co-author Dr. Lawrence Agodoa, who specializes in kidney diseases at the National Institutes of Health. "But the good news is that we have a new tool — the ACE inhibitor — to improve the health of a large number of African Americans and others who have this type of kidney disease."
The African American Study of Kidney Disease and Hypertension (AASK) treated 1,094 patients ages 18 to 70 years with mild kidney disease of hypertension. Investigators compared a usual or standard blood pressure goal of 140/90 mm Hg in 554 patients against a lower goal of 125/75 mm Hg in 540 patients. They also compared three classes of antihypertensives: an ACE inhibitor (ramipril, Altace®), a dihydropyridine calcium channel blocker (CCB) (amlodipine, Norvasc®), and a beta blocker (metoprolol, Toprol XL®). Patients were followed for 3 to 6.4 years at 21 centers. The study ended September 2001.
The ACE inhibitor reduced by 22 percent the risk of reaching the clinical end-points of kidney failure, death or a 50-percent drop in kidney function compared to the beta blocker, and by 38 percent compared to the CCB. The CCB was withdrawn as a primary treatment in September 2000 after data comparing it to the ACE inhibitor showed that the latter drug slowed kidney disease by 36 percent and reduced the risk of kidney failure and death by 48 percent in patients who had at least a gram of protein in the urine. Whereas 155 patients on the beta blocker reached an end-point, only 126 on the ACE inhibitor did. Roughly equal numbers in the two blood pressure groups reached an end-point, 167 in the usual and 173 in the low goal groups.
"The results of this trial will significantly improve the health of thousands of African Americans who suffer from kidney disease due to hypertension" said Dr. John Ruffin, director of the National Center on Minority Health and Health Disparities, which co-funded AASK. "The study also demonstrates the benefit of focusing research on populations most affected."
In the final analysis, even patients with low levels of urine protein benefited greatly from the ACE inhibitor and to a lesser degree from the beta blocker. Both drugs reduce protein in the urine, rising levels of which are an indication of worsening kidney disease, a cause of more damage, and a predictor of death from heart disease and stroke. Within 6 months of starting AASK, patients on the CCB had a 58 percent increase in urine protein. In contrast, patients on the beta blocker had a 15 percent decrease in urine protein and those on the ACE inhibitor had a 20 percent decrease. The ACE inhibitor reduced by 55 percent the risk of developing high levels of urine protein (>300 mg a day) and the beta blocker reduced the risk by 35 percent.
Neither the low blood pressure goal nor any of the drugs stopped the decline in glomerular filtration rate (GFR), which drops as kidney disease progresses. However, regardless of treatment group, GFR dropped more rapidly in patients who had higher levels of urine protein. GFR declined by 1.35 mL/min per 1.73 m2 in patients who started AASK with low levels of urine protein (≤300 mg a day) compared to a decline of 4.09 mL/min per 1.73 m2 in patients with higher urine protein (>300 mg a day).
AASK also showed that while high blood pressure may be more severe and therefore more difficult to control in African Americans, it is feasible. Only 20 percent of patients entered the study with blood pressure levels below the target of 140/90 mm Hg for a general population. Within 14 months, nearly 79 percent of people in the low-goal group and nearly 42 percent in the usual-goal group had lowered pressures to 140/90 mm Hg.
Drugs compared in the study remain important treatments for high blood pressure, helping to reduce the risk of stroke and kidney and heart disease. The Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure now recommends that people with kidney disease, hypertension and protein in the urine achieve and maintain blood pressure at or below 130/85 mm Hg.
"People who have kidney disease of hypertension and any protein in the urine should be given the benefit of an ACE inhibitor, unless the drug is contraindicated, along with a diuretic" said Agodoa, who sits on the JNC and heads the NIDDK Office of Minority Health Research Coordination. "And anyone who also has heart disease or diabetes, as so many do, should try to reach the JNC goal of 130/85 mm Hg."
Kidney failure is a major expense in the United States, costing the Government, patients and insurers nearly $20 billion in 2000. Hypertension is a leading cause, accounting for 25 percent (87,000) of the nearly 379,000 people treated for kidney failure in 2000. Black Americans are six times more likely than whites to develop kidney failure from hypertension and account for 32 percent (122,000) of all treated patients.
Notes to Editors: AASK was funded by the National Institute of Diabetes & Digestive & Kidney Diseases; the National Center on Minority Health & Health Disparities; and the National Center for Research Resources of the National Institutes of Health. Study drugs were provided by Pfizer Inc, AstraZeneca Pharmaceuticals, and King Pharmaceuticals Inc.
