Randomized Design of ALLHAT BP Trial

Transcription

1 Outcomes in Hypertensive Black and Nonblack Patients Treated with Chlorthalidone, Amlodipine, and Lisinopril* *Wright JT, Dunn JK, Cutler JA et al. JAMA 2005:293:

2 42,418 High-risk hypertensive patients Randomized Design of ALLHAT BP Trial Consent / Randomize Amlodipine Chlorthalidone Doxazosin Lisinopril Follow until death or end of study (4-8 8 years, mean 4.9 years)

3 Race Subgroup Analysis ALLHAT reported no differences in the primary CHD outcome, but overall superiority of thiazide- type diuretic for first-step step therapy of hypertension based on differences in secondary outcomes The population of blacks with hypertension has the highest morbidity and mortality from hypertension of any population group in the U.S. Race was a prespecified subgroup for ALLHAT

4 Baseline Characteristics by Race (Chlorthalidone, Amlodipine, Lisinopril) Black Non-Black N 11,792 21,565 Age mean (sd) 66.3 (7.8) 67.2 (7.6) Women (%) SBP mean (sd) (15.8) (15.6) DBP mean (sd) 84.8 (10.2) 83.6 (10.0) Current smokers (%) ASCVD (%) Diabetes Classification (%) Diabetes Impaired fasting glucose Normoglycemic LVH by ECG (%) HDL-C mean (sd) mg/dl 51.7 (15.6) 44.3 (13.5)

5 Blood Pressure at 5 Years by Race Chlorthalidone Amlodipine Lisinopril SBP mean (sd) DBP mean (sd) SBP/DBP compared with chlorthalidone Black (15.8) (15.3) (19.7) (14.8) (14.6) (16.7) Black 77.4 (10.0) 76.3 (10.1) 78.0 (11.4) 74.4 (9.5) 73.6 (9.6) 74.1 (10.1) Black / * / +1.4* Nonblack Nonblack Nonblack / -1.1* +0.5 / -0.5 * P < compared to Chlorthalidone

6 BP Results by Treatment Group by Race Black-Chlor Black Amlod Black Lisin Nonblack Chlor Nonblack Amlod Nonblack Lisin mm Hg SBP mm Hg DBP Years Years

7 % on 3+ Antihypertensive Drugs by Randomized Group and Race at 5 Years Chlorthalidone Amlodipine Lisinopril 60 Percent Black Non-Black

8 BP Control (<140/90 mm Hg) and Mean BP by Randomized Group and Race at 5 Years Chlorthalidone Amlodipine Lisinopril Percent /78 136/76 139/79 133/74 134/74 134/74 0 Black Non-Black

9 Serum Potassium (mean mmol/l) by Treatment Group and Race Chlor Amlod Lisin Black Baseline Years Years Non-Black Baseline Years Years

10 Serum Cholesterol (mean mg/dl) by Treatment Group and Race Chlor Amlod Lisin Black Baseline Years Years Non-Black Baseline Years Years

11 Fasting Glucose (mean mg/dl) by Treatment Group and Race Chlor Amlod Lisin Black Baseline Years Years Non-Black Baseline Years Years

12 Fasting Glucose 126 mg/dl by Treatment Group and Race Chlor Amlod Lisin Black Baseline 31% 32% 31% 2 Years 35% 34% 29% 4 Years 34% 33% 28% Non-Black Baseline 28% 28% 28% 2 Years 32% 28% 28% 4 Years 32% 30% 29%

13 Black vs. Non-Black Amlodipine/Chlorthalidone Relative Risk and 95% Confidence Intervals Nonfatal MI + CHD Death All-Cause Mortality Combined CHD Combined CVD Stroke End Stage Renal Disease Heart Failure Black 1.01 ( ) 0.97 ( ) 1.03 ( ) 1.06 ( ) 0.93 ( ) 1.15 ( ) 1.46 ( ) Non-Black 0.97 ( ) 0.94 ( ) 0.99 ( ) 1.04 ( ) 0.93 ( ) 1.08 ( ) 1.32 ( ) Favors Amlodipine Favors Chlorthalidone Favors Amlodipine Favors Chlorthalidone

14 Black vs. Non-Black Lisinopril/Chlorthalidone Relative Risk and 95% Confidence Intervals Nonfatal MI + CHD Death All-Cause Mortality Combined CHD Combined CVD Stroke End Stage Renal Disease Heart Failure Black 1.10 ( ) 1.06 ( ) 1.15 ( ) 1.19 ( ) 1.40 ( ) 1.29 ( ) 1.30 ( ) Non-Black 0.94 ( ) 0.97 ( ) 1.01 ( ) 1.06 ( ) 1.00 ( ) 0.93 ( ) 1.13 ( ) Favors Lisinopril Favors Chlorthalidone Favors Lisinopril Favors Chlorthalidone

15 Heart Failure Rate for Blacks by Treatment Group Cumulative HF Rate, % Chlorthalidone Amlodipine Lisinopril No. at Risk Years to HF Amlodipine Lisinopril Chlorthalidone

16 Cumulative HF Rate, % Heart Failure Rate for Non-Blacks By Treatment Group Chlorthalidone Amlodipine Lisinopril No. at Risk Years to HF Amlodipine Lisinopril Chlorthalidone

17 ANGIOEDEMA Total Chlorthalidone 8 / 15, % Lisinopril 41 / 9, % Blacks 2 / 5,369 <0.1% 23 / 3, % Nonblacks 6 / 9, % 18 / 5, % p<.001 p<.001 p=.002 There were 3 cases (<0.1%) of angioedema in the amlodipine group (comparison to chlorthalidone not significant).

18 Antihypertensive Trial: Implications Diuretics should be the drug of choice for initial therapy of hypertension. The evidence for this recommendation is even stronger for Black hypertensive patients.. For the patient who cannot take a diuretic (which should be an unusual circumstance), CCB s and ACEI s may be considered. However, in Black hypertensive patients, ACEI s should be considered second-line therapy. Most hypertensive patients require more than one drug. Diuretics should generally be part of the antihypertensive regimen. Lifestyle advice should also be provided.

19 Extra Slides

20 Blacks Amlodipine/Chlorthalidone Relative Risk and 95% Confidence Intervals Nonfatal MI + CHD Death 1.01 ( ) All-Cause Mortality 0.97 ( ) Combined CHD 1.03 ( ) Combined CVD 1.06 ( ) Stroke 0.93 ( ) Heart Failure 1.46 ( ) End Stage Renal Disease 1.15 ( ) Favors Amlodipine Favors Chlorthalidone

21 Blacks Lisinopril/Chlorthalidone Relative Risk and 95% Confidence Interval Nonfatal MI + CHD Death 1.10 ( ) All-Cause Mortality 1.06 ( ) Combined CHD 1.15 ( ) Combined CVD 1.19 ( ) Stroke 1.40 ( ) Heart Failure 1.30 ( ) End Stage Renal Disease 1.29 ( ) Favors Lisinopril Favors Chlorthalidone

22 Non-Blacks Amlodipine/Chlorthalidone Relative Risk and 95% Confidence Intervals Nonfatal MI + CHD Death 0.97 ( ) All-Cause Mortality 0.94 ( ) Combined CHD 0.99 ( ) Combined CVD 1.04 ( ) Stroke 0.93 ( ) Heart Failure 1.32 ( ) End Stage Renal Disease 1.08 ( ) Favors Amlodipine Favors Chlorthalidone

23 Non-Blacks Lisinopril/Chlorthalidone Relative Risk and 95% Confidence Intervals Nonfatal MI + CHD Death 0.94 ( ) All-Cause Mortality 0.97 ( ) Combined CHD 1.01 ( ) Combined CVD 1.06 ( ) Stroke 1.00 ( ) Heart Failure 1.13 ( ) End Stage Renal Disease 0.93 ( ) Favors Lisinopril Favors Chlorthalidone