Lower BP Goal in Black CKD Patients

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ACE inhibitors superior to amlodipine for nondiabetic hypertensive renal disease, data confirm.

 

NEW ORLEANS—An extended follow-up of patients in the African American Study of Kidney Disease (AASK) confirms that ACE inhibitors work better than amlodipine in treating nondiabetic hypertensive CKD in black patients.

 

The study, presented here at the 23rd annual scientific meeting of the American Society of Hypertension, showed no significant benefit in reducing BP to a lower goal than the standard, except in patients with a baseline urinary protein/creatinine ratio greater than 0.22.

 

More than 10 years of follow-up are now available for AASK participants. The main results from the initial trial phase, which involved 1,094 patients, were published in 2002. They showed that the ACE inhibitor ramipril was more effective than the calcium channel blocker amlodipine and the beta blocker metoprolol as initial therapy in slowing the progression of hypertensive renal disease.

 

The largest difference between therapies was observed in patients with a urinary protein/creatinine ratio greater than 0.22 (representing about 300 mg/day of protein).

 

Investigators observed no difference in progression of renal disease between participants randomized to a lower goal for mean arterial pressure (less than 92 mm Hg) compared with 102-107 mm Hg, regardless of the urinary protein/creatinine ratio.

 

The second AASK phase (the cohort phase), which included 691 subjects, was completed in June 2007. At the end of the initial phase, all participants received recommended BP therapy with ramipril (or an angiotensin receptor blocker [ARB]) to achieve a BP goal below 130/80 mm Hg. As in the first phase, the primary outcome was a composite of a doubling of serum creatinine from the trial's baseline, progression to end-stage renal disease, or death.

 

During the initial phase, there was a separation of 13 mm Hg in BP between the groups randomized to the usual and lower BP goals. This disappeared in the cohort phase in which all patients were treated to the lower goal.

 

In the initial phase, ramipril-treated patients had a 22% reduced risk of the primary end point compared with metoprolol-treated patients and a 38% reduced risk compared with amlodipine.

“In the cohort phase, a trend toward a persistence of the benefit with the ACE inhibitor was seen,” said Jackson Wright, MD, professor of medicine and director of the hypertension program at Case Western University in Cleveland.

 

During the cohort phase, initial randomization to ramipril was associated with a nonsignificant 12% reduction in the incidence of the primary end point compared with metoprolol and a nonsignificant 19% reduction compared with amlodipine, even though all patients had been switched to the ACE inhibitor (or ARB) for the open-label extension phase.

 

As in the first phase, there was no difference on the primary outcome between patients randomized to the usual or lower BP goals in the extension phase, he said.

 

In the trial phase, the baseline level of proteinuria did not affect the incidence of the primary outcome between patients assigned to the different blood pressure goals.

 

However, a possible long-term benefit of initial assignment to the lower BP goal was observed in patients with a baseline urinary protein/creat-inine ratio greater than 0.22, Dr. Wright said.

 

In the extension phase, among the participants who had a urinary protein/creatinine ratio greater than 0.22, there was a trend toward a reduction in the incidence of the primary outcome in those initially randomized to the lower BP goal versus the usual goal. There was no difference in outcome between the lower and usual BP goals among the patients with a baseline urinary protein/creatinine ratio of 0.22 or less.

 

“What's important, clearly for patients with significant proteinuria, is to get their blood pressure down as low as possible,” he said. This is consistent with current guidelines for a lower BP goal in CKD patients. AASK findings, however, cannot confirm the recommendation to treat to a lower goal in patients with a lesser degree of proteinuria, he said.

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