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Introduction

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

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Introduction

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  1. CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION RATE (3 GROUPS by GFR) 6/5/2006 - 1

  2. 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

  3. 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

  4. 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 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.

  5. 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

  6. Blood Pressure at 4 Years by Treatment Group and Baseline GFR 6/5/2006 - 6

  7. Evaluating Treatment Effects by Subgroup Interaction – Use subgroup estimates of treatment effects No interaction – Use estimate of treatment effect in total population 6/5/2006 - 7

  8. ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone 6/5/2006 - 8

  9. ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone 6/5/2006 - 9

  10. ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment in Diabetic Participants – Amlodipine vs Chlorthalidone 6/5/2006 - 10

  11. ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment in Diabetic Participants – Lisinopril vs Chlorthalidone 6/5/2006 - 11

  12. ALLHAT Combined CVD by Baseline GFR & Treatment - Amlodipine vs Chlorthalidone 6/5/2006 - 12

  13. ALLHAT Combined CVD by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone 6/5/2006 - 13

  14. ALLHAT Combined CVD by Baseline GFR & Treatment in Diabetic Participants - Amlodipine vs Chlorthalidone 6/5/2006 - 14

  15. ALLHAT Combined CVD by Baseline GFR & Treatment in Diabetic Participants - Lisinopril vs Chlorthalidone 6/5/2006 - 15

  16. ALLHAT Stroke by Baseline GFR & Treatment - Amlodipine vs Chlorthalidone 6/5/2006 - 16

  17. ALLHAT Stroke by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone 6/5/2006 - 17

  18. ALLHAT Stroke by Baseline GFR & Treatment in Diabetic Participants - Amlodipine vs Chlorthalidone 6/5/2006 - 18

  19. ALLHAT Stroke by Baseline GFR & Treatment in Diabetic Participants - Lisinopril vs Chlorthalidone 6/5/2006 - 19

  20. ALLHAT Heart Failure by Baseline GFR & Treatment -Amlodipine vs Chlorthalidone 6/5/2006 - 20

  21. ALLHAT Heart Failure by Baseline GFR & Treatment - Lisinopril vs Chlorthalidone 6/5/2006 - 21

  22. ALLHAT Heart Failure by Baseline GFR & Treatment in Diabetic Participants - Amlodipine vs Chlorthalidone 6/5/2006 - 22

  23. ALLHAT Heart Failure by Baseline GFR & Treatment in Diabetic Participants - Lisinopril vs Chlorthalidone 6/5/2006 - 23

  24. 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

  25. 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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