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ALLHAT. CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION RATE (4 GROUPS by GFR). ALLHAT. Introduction. Over 13 million Americans are estimated to have chronic kidney disease (CKD)

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Allhat

ALLHAT

CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION RATE (4 GROUPS by GFR)

6/5/2006 - 1


Introduction

ALLHAT

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% (n=7116) of ALLHAT participants had an estimated GFR <60 ml/min/1.73m2 at baseline

6/5/2006 - 2


Other studies

ALLHAT

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

6/5/2006 - 3


Allhat

ALLHAT

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.)

** p<.05 compared with normal GFR

***p<0.022, amlodipine (28%) vs. chlorthalidone (31%) in participants with GFR 30-59.


Allhat

ALLHAT

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 <0.001 vs. GFR90+

6/5/2006 - 5


Blood pressure at 4 years by treatment group and baseline gfr

ALLHAT

Blood Pressure at 4 Years by Treatment Group and Baseline GFR

6/5/2006 - 6


Evaluating treatment effects by subgroup

Evaluating Treatment Effects by Subgroup

Interaction – Use subgroup estimates of treatment effects

No interaction – Use estimate of treatment effect in total population

1 / 10 / 2005 - 7


Allhat

ALLHAT

CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

6/5/2006 - 8


Allhat

ALLHAT

CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

6/5/2006 - 9


Allhat

ALLHAT

CHD (Nonfatal MI & Fatal CHD) by Baseline GFR

& Treatment in Diabetic Participants –

Amlodipine vs Chlorthalidone

6/5/2006 - 10


Allhat

ALLHAT

CHD (Nonfatal MI & Fatal CHD) by Baseline GFR

& Treatment in Diabetic Participants –

Lisinopril vs Chlorthalidone

6/5/2006 - 11


Allhat

ALLHAT

Combined CVD by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

6/5/2006 - 12


Allhat

ALLHAT

Combined CVD by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

6/5/2006 - 13


Allhat

ALLHAT

Combined CVD by Baseline GFR

& Treatment in Diabetic Participants –

Amlodipine vs Chlorthalidone

6/5/2006 - 14


Allhat

ALLHAT

Combined CVD by Baseline GFR

& Treatment in Diabetic Participants –

Lisinopril vs Chlorthalidone

6/5/2006 - 15


Allhat

ALLHAT

Stroke by Baseline GFR & Treatment –

Amlodipine vs Chlorthalidone

6/5/2006 - 16


Allhat

ALLHAT

Stroke by Baseline GFR & Treatment –

Lisinopril vs Chlorthalidone

6/5/2006 - 17


Allhat

ALLHAT

Stroke by Baseline GFR

& Treatment in Diabetic Participants –

Amlodipine vs Chlorthalidone

6/5/2006 - 18


Allhat

ALLHAT

Stroke by Baseline GFR

& Treatment in Diabetic Participants –

Lisinopril vs Chlorthalidone

6/5/2006 - 19


Allhat

ALLHAT

Heart Failure by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

6/5/2006 - 20


Allhat

ALLHAT

Heart Failure by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

6/5/2006 - 21


Allhat

ALLHAT

Heart Failure by Baseline GFR

& Treatment in Diabetic Participants –

Amlodipine vs Chlorthalidone

6/5/2006 - 22


Allhat

ALLHAT

Heart Failure by Baseline GFR

& Treatment in Diabetic Participants –

Lisinopril vs Chlorthalidone

6/5/2006 - 23


Discussion

ALLHAT

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.

6/5/2006 - 24


Conclusion

ALLHAT

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.

6/5/2006 - 25


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