RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR FILT

1
RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS
STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR
FILTRATION RATE (GFR)
2
Introduction

• Hypertension is the second most common cause of
  end-stage renal disease (ESRD) in the US
• Hypertension is a key factor contributing to
  progression of chronic kidney disease
• Successful treatment of hypertension is important
  in slowing down progression of renal disease

3
Background

• In diabetic (DM) and nondiabetic (NDM)
  hypertensive patients with established chronic
  renal insufficiency and proteinuria, inhibition
  of the renin angiotensin axis is suggested to be
  superior to conventional therapy in slowing
  decline in renal function
• Few studies directly compared effects of
  different classes of antihypertensive drug
  therapy on decline in renal function in
  hypertensive patients with mild reduction in
  glomerular filtration rate (GFR).

4
Overall Results Renal Outcomes

• In the ALLHAT study population as a whole, no
  difference was noted in the risk of ESRD with
  chlorthalidone compared to amlodipine and
  lisinopril
• Estimated GFR was higher at the end of the study
  in patients randomized to amlodipine compared to
  chlorthalidone.

5
Objective
Post-hoc analysis of the ALLHAT study to
determine whether treatment with a calcium
channel blocker or an ACE inhibitor, each versus
a diuretic, lowers incidence of renal outcomes in
high risk hypertensive patients stratified by
baseline GFR.
6
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.
7
eGFR During the Course of the Study (Baseline
eGFR 90)





plt0.05 vs. Chlorthalidone Estimated GFR (eGFR)
calculated from the simplified MDRD equation
8
eGFR During the Course of the Study (Baseline
eGFR 60-89)



plt0.05 vs. Chlorthalidone Estimated GFR (eGFR)
calculated from the simplified MDRD equation
9
eGFR During the Course of the Study (Baseline
eGFR lt60)



plt0.05 vs. Chlorthalidone Estimated GFR (eGFR)
calculated from the simplified MDRD equation
10
Evaluating Treatment Effects by Subgroup
Interaction Use subgroup estimates of treatment
effects No interaction Use estimate of
treatment effect in total population
11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
17
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline Diabetes Treatment
Amlodipine vs Chlorthalidone
18
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline GFR Treatment Amlodipine
vs Chlorthalidone
19
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline GFR Treatment Diabetic
Participants Amlodipine vs Chlorthalidone
20
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline Diabetes Treatment
Lisinopril vs Chlorthalidone
21
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline GFR Treatment Lisinopril
vs Chlorthalidone
22
End Stage Renal Disease or 50 or Greater Decline
in GFR by Baseline GFR Treatment Diabetic
Participants Lisinopril vs Chlorthalidone
23
Summary

• The overall study results of no difference in
  ESRD and the composite (ESRD/50 decline in GFR)
  for the lisinopril vs. chlorthalidone and
  amlodipine vs. chlorthalidone comparisons was
  consistent across diabetes, GFR, and diabetes-GFR
  subgroups.

24
Discussion

• High risk hypertensive patients are at higher
  risk for CVD than ESRD
• Risk of ESRD is higher in diabetic participants,
  and those with reduced GFR at baseline
• 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

25
Strengths Limitations

• Strength -
• The number of patients with moderate reduction in
  GFR, and the number of patients developing ESRD
  are higher in ALLHAT compared to any other renal
  study, including AASK, RENAAL and IDNT
• Limitation
• Proteinuria is an independent predictor of
  decline in renal function. Information about
  proteinuria was not available in ALLHAT
  participants.

26
Conclusion

• In high risk hypertensive patients with reduced
  GFR, amlodipine and lisinopril are not superior
  to chlorthalidone in reducing the rate of
  development of ESRD and significant decrements in
  GFR