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ALLHAT

ALLHAT. RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR). ALLHAT. Introduction. Hypertension is the second most common cause of end-stage renal disease (ESRD) in the US

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ALLHAT

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

  2. ALLHAT 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. ALLHAT 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. ALLHAT 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. ALLHAT 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. 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.

  7. ALLHAT eGFR During the Course of the Study (Baseline eGFR ≥90) * * * * * * p<0.05 vs. Chlorthalidone Estimated GFR (eGFR) calculated from the simplified MDRD equation

  8. ALLHAT eGFR During the Course of the Study (Baseline eGFR 60-89) * * * * p<0.05 vs. Chlorthalidone Estimated GFR (eGFR) calculated from the simplified MDRD equation

  9. ALLHAT eGFR During the Course of the Study (Baseline eGFR <60) * * * * p<0.05 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

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  17. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline Diabetes & Treatment – Amlodipine vs Chlorthalidone

  18. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

  19. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline GFR & Treatment – Diabetic Participants Amlodipine vs Chlorthalidone

  20. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline Diabetes & Treatment – Lisinopril vs Chlorthalidone

  21. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

  22. ALLHAT End Stage Renal Disease or 50% or Greater Decline in GFR by Baseline GFR & Treatment – Diabetic Participants Lisinopril vs Chlorthalidone

  23. ALLHAT 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. ALLHAT 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. ALLHAT 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. ALLHAT 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

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