AASK

From Wiki Journal Club
Jump to: navigation, search
Wright JT Jr., et al. "Intensive blood-pressure control in hypertensive chronic kidney disease". JAMA. 2002. 288(19):2421-2431.
PubMedFull textPDF

Clinical Question

In African Americans with hypertensive kidney disease, does intensive blood pressure control slow progression of CKD more than conservative BP control?

Bottom Line

Among African Americans with hypertensive kidney disease, intensive blood pressure control targeting MAP <92 mm Hg did not slow progression of kidney disease compared to conservative blood pressure control targeting MAP 102-107 mm Hg. Use of ACE-inhibitors slowed rate of GFR decline.

Major Points

While JNC 7 guidelines recommend conservative BP control (goal SBP<140 for most and <150 for elderly), the SPRINT trial demonstrated a mortality benefit from more intensive BP control driven primarily by reduction in CHF. Among patients with hypertensive nephropathy, it is not known whether intense BP control provides additional benefit beyond standard BP control. Few trials have examined this comparison, with short follow-up and inconsistent results. The AASK trial was a large trial examining this questions in African Americans, finding no significant differences in progression of CKD with intensive (average BP 128/78) vs. conservative BP control (average BP 141/85), suggesting that a BP goal of 140/80 is reasonable even for patients with CKD.

Guidelines

Design

  • Multicenter, randomized, 2x3 factorial, controlled trial
  • N=1,094 African-American individuals
    • 2x3, BP (open-label):
      • Lower BP (n=540)
      • Usual BP (n=554)
    • 2x3, initial BP medication (blinded):
      • Beta blocker (n=441)
      • ACE-inhibitor (n=436)
      • CCB (n=217)
  • Setting: 21 centers in the US
  • Enrollment: 1995-1998
  • Median follow-up: About 4 years
  • Analysis: Not disclosed, likely intention-to-treat
  • Primary outcomes:
    • Rate of change in eGFR
    • Progression of CKD or all-cause mortality

Population

Inclusion Criteria

  • African-American
  • Age 18-70
  • Diastolic blood pressure ≥95 mm Hg
  • Hypertensive renal disease
  • eGFR 20-65 mL/min/1.73 m2

Exclusion Criteria

  • Diabetes
  • Urine protein:creatinine >2.5
  • Malignant hypertension in prior 6 months
  • Heart failure
  • Serious comorbidities

Baseline Characteristics

From the lower BP arm.

  • Demographics: Age 54 years, female sex 38%
  • Physiological measurements: Weight 89 kg, BMI 20.5 kg/m2, BP 152/96 mm Hg, MAP 115 mm Hg
  • Renal data: eGFR 46 mL/min/1.73 m2, U protein:creatinine ≥0.22 34%
    • Males: Creatinine 2.2 mg/dL, U protein:creatinine 0.33, U protein 0.61 g/24h
    • Females: Creatinine 1.7 mg/dL, U protein:creatinine 0.28, U protein 0.36 g/24h
  • Antihypertensive use: 97%
    • Type: Diuretics 62%, ACE-inhibitors 38%, beta-blockers 28%, CCB 65%, dihydropyridine CCB 50%

Interventions

  • Participants were randomized to a group:
    • Lower BP - Target MAP ≤92 (mean achieved: 128/78 mm Hg)
    • Usual BP - Target MAP 102-107 (mean achieved: 141/85 mm Hg)
  • Participants were also randomzied to an initial drug therapy:
    • ACE-inhibitor - Ramipril 2.5-10 mg/day
    • Beta-blocker - Metoprolol succinate 50-200 mg/day
    • CCB - Amlodipine 5-10 mg/day
  • All participants were uptitrated to the highest tolerated dose of their initial drug therapy before starting additional therapies, which were furosemide, doxazosin, clonidine, and hydralazine or minoxidil
  • As amlodipine is associated with an acute change in GFR at discontinuation, GFR comparisons were censored at the time of discontinuation of this medication. The median GFR follow-up was 3.8 years for CCB vs. 4.1 years for ACE-inhibitor and beta-blocker.

Outcomes

RR is risk reduction. The first presented group in the comparison is the reference. I.e., ACE-inhibitor associated with a +0.61 increase in GFR when compared to beta blocker.

Primary Outcomes

Rate of change in eGFR (total slope)
Lower BP vs. usual BP: -0.25 mL/min/1.73 m2/year (P=0.24)
ACE-inhibitor vs. beta-blocker: +0.61 mL/min/1.73 m2/year (P=0.007)
CCB vs. beta-blocker: +1.08 mL/min/1.73 m2/year (P=0.004)
ACE-inhibitor vs. CCB: -0.34 mL/min/1.73 m2/year (P=0.38)
Progression of CKD or all-cause mortality

Progression of CKD was defined as reduction in eGFR by ≥50% or drop by 25 mL/min/1.73 m2, or ESRD.

Lower BP vs. usual BP: 2% RR (95% CI -22 to 21; P=0.85)
ACE-inhibitor vs. beta-blocker: 22% RR (95% CI 1 to 38; P=0.04)
CCB vs. beta-blocker: 20% RR (95% CI -10 to 41; P=0.17)
ACE-inhibitor vs. CCB: 38% RR (95% CI 14 to 56; P=0.004)

Secondary Outcomes

Progression of CKD
Lower BP vs. usual BP: -2% RR (95% CI -31 to 20; P=0.87)
ACE-inhibitor vs. beta-blocker: 22% RR (95% CI -2 to 41; P=0.07)
CCB vs. beta-blocker: 24% RR (95% CI -9 to 47; P=0.13)
ACE-inhibitor vs. CCB: 40% RR (95% CI 14 to 59; P=0.006
ESRD or all-cause mortality
Lower BP vs. usual BP: 12% RR (95% CI -13 to 32; P=0.31)
ACE-inhibitor vs. beta-blocker: 21% RR (95% CI -5 to 40; P=0.11)
CCB vs. beta-blocker: 42% RR (95% CI 17 to 60; P=0.003)
ACE-inhibitor vs. CCB: 49% RR (95% CI 26 to 65; P<0.001)
ESRD
Lower BP vs. usual BP: 6% RR (95% CI -29 to 31; P=0.72)
ACE-inhibitor vs. beta-blocker: 22% RR (95% CI -10 to 45; P=0.16)
CCB vs. beta-blocker: 59% RR (95% CI 36 to 74; P<0.001)
ACE-inhibitor vs. CCB: 59% RR (95% CI 36 to 74; P<0.001)

Additional Outcomes

BP achieved
Lower BP: 128/78 mm Hg
Usual BP: 141/85 mm Hg
ACE-inhibitor: 135/82 mm Hg
CCB: 133/81 mm Hg
Beta-blocker: 135/81 mm Hg

Subgroup Analysis

The investigators assessed by urinary protein:creatinine threshold of 0.22, details are on page 2427. Details of this subgroup analysis are incomplete in the report but there were "slight trends" for benefit of lower BP in those with a ratio >0.22 and benefit for higher BP in those with ratio ≤0.22.

Adverse Events

There were similar rates of adverse events except for more cough and angioedema in the ACE-inhibitor group.

Criticisms

  • The cohort phase was not a randomized trial, since all the patients had the same blood pressure target.
  • Adjustment of therapy was based on blood pressure as assessed by standard office readings, not on ambulatory blood pressure.
  • Significant subgroup results should be interpreted cautiously, given the potential for chance findings even when the subgroup is pre- specified.

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases; by the Office of Research in Minority Health (now the National Center on Minority Health and Health Disparities)
  • National Institutes of Health (M01 RR-00080, M01 RR-00071, M0100032, P20-RR11145, M01 RR00827, M01 RR00052, 2P20 RR11104, RR029887, and DK 2818-02)
  • King Pharmaceuticals, which provided monetary support and antihypertensive medications to each clinical center
  • Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn, which donated antihypertensive medications

Further Reading