CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATIO

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CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE
PATIENTS STRATIFIED BY BASELINE GLOMERULAR
FILTRATION RATE (3 GROUPS by GFR)
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Introduction

• Over 13 million Americans are estimated to have
  chronic kidney disease (CKD)
• Patients with CKD are at very high risk for
  cardiovascular disease (CVD)
• There are limited data about the comparative
  effects of antihypertensive therapy on CVD
  outcomes in CKD patients
• Since risk of CVD is much higher than risk for
  ESRD in CKD patients, choices of therapy need to
  be guided by effects on CVD outcomes
• 17.7 (n7116) of ALLHAT participants had an
  estimated GFR lt60 ml/min/1.73m2 at baseline

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Other Studies

• Many trials that studied patients with CKD do not
  have adequate assessment / reporting or power to
  evaluate CV events
• HOPE demonstrated increased CV risk in patients
  with renal insufficiency and that ramipril
  reduced risk in this subgroup compared to placebo
• IDNT and RENAAL showed similar CV event rates
  with ARB vs CCB (IDNT) and placebo (RENAAL),
  except hospitalization for first heart failure in
  RENAAL was lower with the ARB
• AASK (beta blocker, ACE, CCB) showed no
  difference in CV event rates

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Baseline Characteristics Stratified By Estimated
GFR
Estimated (eGFR) (ml/min/1.73 m2) calculated by
simplified MDRD equation (Levey et al., J Am Soc
Nephrol 11, A 0828. 2000.) plt.05 compared with
normal GFR NOTE Within each GFR stratum, there
was no significant difference in these
characteristics between patients assigned to
amlodipine or lisinopril compared with patients
assigned to chlorthalidone.
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Relative Risk of Combined CVD by Baseline GFR
Group(Adjusted for Age, Race, Gender, BMI, SBP,
DBP, HDL-cholesterol, LDL-cholesterol, fasting
triglycerides, history of diabetes, and cigarette
smoking)


Estimated (eGFR) (ml/min/1.73 m2) calculated by
simplified MDRD equation P lt0.001 vs. GFR90
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Blood Pressure at 4 Years by Treatment Group and
Baseline GFR
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Evaluating Treatment Effects by Subgroup
Interaction Use subgroup estimates of treatment
effects No interaction Use estimate of
treatment effect in total population
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CHD (Nonfatal MI Fatal CHD) by Baseline GFR
Treatment Amlodipine vs Chlorthalidone
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CHD (Nonfatal MI Fatal CHD) by Baseline GFR
Treatment Lisinopril vs Chlorthalidone
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CHD (Nonfatal MI Fatal CHD) by Baseline GFR
Treatment in Diabetic Participants Amlodipine
vs Chlorthalidone
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CHD (Nonfatal MI Fatal CHD) by Baseline GFR
Treatment in Diabetic Participants Lisinopril
vs Chlorthalidone
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Combined CVD by Baseline GFR Treatment -
Amlodipine vs Chlorthalidone
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Combined CVD by Baseline GFR Treatment
Lisinopril vs Chlorthalidone
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Combined CVD by Baseline GFR Treatment in
Diabetic Participants - Amlodipine vs
Chlorthalidone
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Combined CVD by Baseline GFR Treatment in
Diabetic Participants - Lisinopril vs
Chlorthalidone
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Stroke by Baseline GFR Treatment - Amlodipine
vs Chlorthalidone
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Stroke by Baseline GFR Treatment Lisinopril
vs Chlorthalidone
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Stroke by Baseline GFR Treatment in Diabetic
Participants - Amlodipine vs Chlorthalidone
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Stroke by Baseline GFR Treatment in Diabetic
Participants - Lisinopril vs Chlorthalidone
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Heart Failure by Baseline GFR Treatment
-Amlodipine vs Chlorthalidone
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Heart Failure by Baseline GFR Treatment -
Lisinopril vs Chlorthalidone
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Heart Failure by Baseline GFR Treatment in
Diabetic Participants - Amlodipine vs
Chlorthalidone
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Heart Failure by Baseline GFR Treatment in
Diabetic Participants - Lisinopril vs
Chlorthalidone
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Discussion

• ALLHAT confirms increased risk for CVD in
  patients with reduced GFR.
• The overall study results of no difference in the
  primary outcome for the lisinopril vs.
  chlorthalidone and amlodipine vs. chlorthalidone
  comparisons was consistent across diabetes, GFR,
  and diabetes-GFR subgroups.

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Conclusion
In high risk hypertensive patients with impaired
renal function

• Amlodipine and lisinopril are not superior to
  chlorthalidone in preventing fatal CHD/non fatal
  MI
• Chlorthalidone and amlodipine are similar but
  chlorthalidone is superior to lisinopril in
  reducing combined CVD events independent of level
  of renal function.