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25 juin 2016

AASK? : African American Study of Kidney Disease and Hypertension.


Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.

To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.

Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.

A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.

Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual ; n = 554) or 92 mm Hg or less (lower ; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d ; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d ; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d ; n = 217). Open-label agents were added to achieve the assigned BP goals.

Rate of change in GFR (GFR slope) ; clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified : lower vs? usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol.

Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year ; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2% ; 95% confidence interval [CI], -22% to 21% ; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38% ; P =.04) and 38% (95% CI, 14%-56% ; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.

No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.
Comment in
Antihypertensive drugs and renal protection. [JAMA. 2003]
Long-term cardiovascular consequences of diuretics vs calcium channel blockers vs angiotensin-converting enzyme inhibitors. [JAMA. 2003]
Hypertension control and kidney disease : some questions answered, many remain. [JAMA. 2002]
PMID 11386927


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Agodoa LY, Appel L, Bakris GL, et al. ; African American Study of Kidney Disease and Hypertension (AASK) Study Group. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis : a randomized controlled trial. JAMA. 2001 Jun 6 ; 285(21):2719-28. PMID 11386927

Grams ME, Li L, Greene TH, Tin A, et al. Estimating time to ESRD using kidney failure risk equations : results from the African American Study of Kidney Disease and Hypertension (AASK). Am J Kidney Dis. 2015 Mar ; 65(3):394-402. PMID 25441435

Bhalla M, Aziz H, Richard E, Lipkowitz MS, Bhatnagar V. Serum potassium predicts time to blood pressure response among African Americans with hypertensive nephrosclerosis. J Hum Hypertens. 2013 Jun ; 27(6):393-6. PMID 23151750

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Toto RD, Greene T, Hebert LA, Hiremath L, Lea JP, Lewis JB, Pogue V, Sika M, Wang X ; AASK Collaborative Research Group. Relationship between body mass index and proteinuria in hypertensive nephrosclerosis : results from the African American Study of Kidney Disease and Hypertension (AASK) cohort. Am J Kidney Dis. 2010 Nov ; 56(5):896-906. PMID 20801567

Appel LJ, Wright JT Jr, Greene T, et al. ; AASK Collaborative Research Group. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010 Sep 2 ; 363(10):918-29. PMID 20818902

Alves TP, Wang X, Wright JT Jr, Appel LJ, Greene T, Norris K, Lewis J ; AASK Collaborative Research Group. Rate of ESRD exceeds mortality among African Americans with hypertensive nephrosclerosis. J Am Soc Nephrol. 2010 Aug ; 21(8):1361-9. PMID 20651163

Onuigbo MA. RAAS blockade, renal failure, ESRD, and death among African Americans in the AASK Posttrial Cohort Study. Arch Intern Med. 2008 Nov 24 ; 168(21):2383-4. PMID 19029505

Taylor AL, Wright JT Jr. Should ethnicity serve as the basis for clinical trial design ? Importance of race/ethnicity in clinical trials : lessons from the African-American Heart Failure Trial (A-HeFT), the African-American Study of Kidney Disease and Hypertension (AASK), and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT?). Circulation. 2005 Dec 6 ; 112(23):3654-60 ; discussion 3666. PMID 16330707

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