7/27/2006 Outcomes in Hypertensive Black and Nonblack Patients Treated with Chlorthalidone, Amlodipine, and Lisinopril* * Wright JT, Dunn JK, Cutler JA et al. JAMA 2005:293: ALLHAT

7/27/2006 Randomized Design of ALLHAT BP Trial 42,418 High-risk hypertensive patients Consent / Randomize AmlodipineChlorthalidoneDoxazosinLisinopril Follow until death or end of study (4-8 years, mean 4.9 years) ALLHAT

7/27/2006 ALLHAT reported no differences in the primary CHD outcome, but overall superiority of thiazide- type diuretic for first-step therapy of hypertension based on differences in secondary outcomes ALLHAT reported no differences in the primary CHD outcome, but overall superiority of thiazide- type diuretic for first-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. 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 Race was a prespecified subgroup for ALLHAT Race Subgroup Analysis ALLHAT

7/27/2006 Baseline Characteristics by Race (Chlorthalidone, Amlodipine, Lisinopril) BlackNon-Black N11,79221,565 Age – mean (sd)66.3 (7.8)67.2 (7.6) Women (%) SBP – mean (sd)146.2 (15.8)146.3 (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/dl51.7 (15.6)44.3 (13.5) ALLHAT

7/27/2006 ChlorthalidoneAmlodipineLisinopril SBP – mean (sd) Black135.0 (15.8)136.1 (15.3)139.1 (19.7) Non- black (14.8)133.8 (14.6)134.2 (16.7) DBP – mean (sd) Black77.4 (10.0)76.3 (10.1)78.0 (11.4) Non- black 74.4 (9.5)73.6 (9.6)74.1 (10.1) ∆ SBP/DBP compared with chlorthalidone Black / * / +1.4* Non- black / -1.1*+0.5 / -0.5 Blood Pressure at 5 Years by Race * P < compared to Chlorthalidone ALLHAT

7/27/2006 Black-ChlorBlack–AmlodBlack–Lisin Nonblack–ChlorNonblack–AmlodNonblack–Lisin BP Results by Treatment Group by Race ALLHAT

7/27/2006 % on 3+ Antihypertensive Drugs by Randomized Group and Race at 5 Years ALLHAT

7/27/2006 BP Control (<140/90 mm Hg) and Mean BP by Randomized Group and Race at 5 Years 135/78136/76139/79133/74 134/74 134/74 ALLHAT

7/27/2006 Serum Potassium (mean mmol/l) by Treatment Group and Race ChlorAmlodLisin BlackBaseline Years Years Non-BlackBaseline Years Years ALLHAT

7/27/2006 Serum Cholesterol (mean mg/dl) by Treatment Group and Race ChlorAmlodLisin BlackBaseline Years Years Non-BlackBaseline Years Years ALLHAT

7/27/2006 Fasting Glucose (mean mg/dl) by Treatment Group and Race ChlorAmlodLisin BlackBaseline Years Years Non-BlackBaseline Years Years ALLHAT

7/27/2006 Fasting Glucose  126 mg/dl by Treatment Group and Race ChlorAmlodLisin BlackBaseline31%32%31% 2 Years35%34%29% 4 Years34%33%28% Non-BlackBaseline28%28%28% 2 Years32%28%28% 4 Years32%30%29% ALLHAT

7/27/2006 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 Favors Amlodipine ( ) 1.15 ( ) 0.93 ( ) 1.06 ( ) 1.03 ( ) 0.97 ( ) 1.01 ( ) Favors Chlorthalidone Non-Black ( ) 1.08 ( ) 0.93 ( ) 1.04 ( ) 0.99 ( ) 0.94 ( ) 0.97 ( ) Favors Amlodipine Favors Chlorthalidon e ALLHAT

7/27/2006 ALLHAT 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 Favors Lisinopril Favors Chlorthalidone Non-Black Favors Lisinopril Favors Chlorthalidone ( ) 0.93 ( ) 1.00 ( ) 1.06 ( ) 1.01 ( ) 0.97 ( ) 0.94 ( )

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

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

7/27/2006 ANGIOEDEMA TotalBlacks Non- blacks Chlorthalidone8 / 15, % 2 / 5,369 <0.1% 6 / 9, % Lisinopril41 / 9, % 23 / 3, % 18 / 5, % p<.001 p=.002 There were 3 cases (<0.1%) of angioedema in the amlodipine group (comparison to chlorthalidone not significant). ALLHAT

7/27/2006 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. ALLHAT

7/27/2006 Extra Slides

7/27/2006 Nonfatal MI + CHD Death1.01 ( ) All-Cause Mortality0.97 ( ) Combined CHD1.03 ( ) Combined CVD1.06 ( ) Stroke0.93 ( ) Heart Failure1.46 ( ) End Stage Renal Disease1.15 ( ) Blacks Amlodipine/Chlorthalidone Relative Risk and 95% Confidence Intervals Favors Amlodipine Favors Chlorthalidone ALLHAT

7/27/2006 Nonfatal MI + CHD Death1.10 ( ) All-Cause Mortality1.06 ( ) Combined CHD1.15 ( ) Combined CVD1.19 ( ) Stroke1.40 ( ) Heart Failure1.30 ( ) End Stage Renal Disease1.29 ( ) Blacks Lisinopril/Chlorthalidone Relative Risk and 95% Confidence Interval Favors Lisinopril Favors Chlorthalidone ALLHAT

7/27/2006 Nonfatal MI + CHD Death0.97 ( ) All-Cause Mortality0.94 ( ) Combined CHD0.99 ( ) Combined CVD1.04 ( ) Stroke0.93 ( ) Heart Failure1.32 ( ) End Stage Renal Disease1.08 ( ) Non-Blacks Amlodipine/Chlorthalidone Relative Risk and 95% Confidence Intervals Favors Amlodipine Favors Chlorthalidone ALLHAT

7/27/2006 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 ( ) Non-Blacks Lisinopril/Chlorthalidone Relative Risk and 95% Confidence Intervals Favors Lisinopril Favors Chlorthalidone ALLHAT