AASK results published: ACE inhibitors rout beta blockers and CCBs in hypertensive renal disease

Shelley Wood

November 19, 2002

Tue, 19 Nov 2002 21:00:00

Cleveland, OH - Full results of the African American Study of Kidney Disease and Hypertension (AASK), showing ACE inhibitors to be superior to beta blockers and calcium channel blockers (CCBs) in slowing progression of renal disease in African Americans with hypertension, have now been published. The results also suggest that aiming for blood pressure (BP) goals below those recommended in current guidelines does not translate into additional slowing of renal disease progression. An editorial accompanying the study, however, claims that the important results will not necessarily "satisfy" physicians.

The AASK was first presented at the 2001 American Heart Association Scientific Sessions, as reported by heartwire . The results, by Dr Jackson T Wright (Case Western Reserve University, Cleveland, OH) et al, appear now in the November 20, 2002 issue of the Journal of the American Medical Association.

The findings effectively trump any lingering concerns over whether ACE inhibitors should be used in African Americans, the authors point out. "Evidence that ACE inhibitors and beta blockers lower BP to a lesser extent in African Americans than others, when used as monotherapy, taken together with the paucity of prospective clinical end point data, has resulted in less use of such agents in African Americans. The AASK is the first outcome trial to demonstrate a renoprotective effect of ACE inhibitors in an African American population."



AASK results

AASK was a 3x2-factorial-designed, multicenter study of 1094 African Americans, randomized to 1 of 2 BP targets, either an aggressive goal of 125/75 mm Hg or the standard target of 140/90 mm Hg. Patients were also randomized to receive 1 of 3 drugs: ramipril (Altace® - Monarch Pharmaceuticals), the beta blocker metoprolol (Toprol® - AstraZeneca AB), or amlodipine (Norvasc® - Pfizer).

The primary end point of the trial, change in glomerular filtration rate (GFR) slope, including both the total and chronic slopes, did not differ significantly among the different drug groups. As well, mean GRF slope was not significantly different between the usual- and low-target BP groups. The secondary end point of the studyregarded as potentially more clinically relevantwas a composite of a 50% decrease in the GFR, an absolute decrease in GFR of 25 mL/min/1.73 m2, end-stage renal disease (ESRD), or death. For this end point, patients in the ramipril group showed a 22% risk reduction compared with the metoprolol and amlodipine groups. Previously released data from AASK had already shown ramipril to be associated with a risk reduction of 38% compared with amlodipine alone, a finding that earlier led to the halt of the amlodipine arm of the trial. No significant differences were observed between the metoprolol and amlodipine arms in terms of the clinical composite outcome.

-SW


In an editorial accompanying the study, Dr Michael H Alderman (Albert Einstein College of Medicine) says that the trial results "are unlikely to satisfy physicians caring for patients such as those in AASK."

Alderman is specifically concerned with the conclusions by Wright and colleagues that the lack of a difference seen between the 2 BP groups in terms of the clinical composite of a 50% reduction in GFR, ESRD, or death suggests that use of lower-than-normal BP goals "as a strategy to prevent progression of hypertensive nephrosclerosis" is not supported.

"That conclusion," writes Alderman, "should be tempered by the fact that both the primary and secondary end points in AASK largely depended on GFR, a surrogate end point for which the relation to health outcomes is, at best, uncertain."

He continues, "In short, the end points for which this study was powered do not provide the information necessary to establish blood pressure goals for these (or other) patients with hypertension. Those physicians who believe that, particularly for high-risk patients such as those in AASK, lower blood pressure levels are better are unlikely to be persuaded by these findings."

To heartwire , Alderman elaborated: "What really matters is not measurements of kidney function, but quality of life and real clinical outcomes, such as strokes and MIs. Doctors aren't going to be convinced that lower might not be better, especially since there's a fair amount of data from clinical trials that suggests that lower might be better....The evidence we have so far is that whatever your blood pressure is, lowering it is probably a good idea."

Not the whole story

The other AASK findings, demonstrating the benefits of ramipril in African American patients, are relevant, Alderman states, although the integration of the AASK results into clinical practice requires careful thought. In AASK, the most common second drug was a diuretic, and, as Alderman points out, no clinical trial has yet shown any antihypertensive agent to produce cardiovascular protection above and beyond that offered by a diuretic.

"Thus, in the absence of clinical trial data to the contrary, particularly in patients with fairly well-maintained renal function...initiation of therapy with a thiazide seems most reasonable, albeit with a low threshold for the addition of an ACE inhibitor and a change to furosemide."

A beta blocker, suggests Alderman, could then be used in patients who require 3 or more drugs for adequate BP control.

Overall, Alderman summarizes, the AASK results "provide important information about renal function and blood pressure control during antihypertensive care in patients with hypertensive nephrosclerosis but insufficient data on both clinical renal effects and cardiovascular outcomes." Physiological functions, he says, are not the "whole story."

"Patients and physicians are best served when clinical decisions can be based on evidence of benefit measured by the duration and quality of life," Alderman concludes.

It is hoped that results of the ALLHAT trial will provide some answers to the questions posed by Alderman. ALLHAT, comparing differences in cardiovascular death and nonfatal MI in patients randomized to a diuretic, ACE inhibitor, calcium blocker, or alpha blocker in hypertension patients, will be released mid-December 2002 and includes approximately 15 000 African Americans.

Alderman also pointed out to heartwire that the 10000-patient ACCORD trial in older diabetics, half of whom have hypertension, will provide some answers to the lower-than-low blood pressure question. One of the strategies being tested in this trial, due out in 2007, is a lower-than-normal BP target.



Related link

1. [HeartWire > News; Nov 13, 2001]


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