Blood Pressure Control By Randomized Drug Group In ALLHAT William C. Cushman, Charles E. Ford, Paula T. Einhorn, Jackson T. Wright, Jr., Richard A. Preston, Barry R. Davis, and Jan N. Basile for the ALLHAT Collaborative Research Group ALLHAT

Disclosure Information William C. Cushman, MD The following relationships exist that may be related to this presentation: Research/grant support: Astra-Zeneca, Kos, Aventis Pharma, King Pharmaceuticals, Boehringer-Ingelheim, Sanofi, BMS, Biovail, Abbott Consultant and/or lectures: Sanofi, Novartis, Pfizer, Sankyo, Forest, Biovail, Abbott, Reddy, First Horizon Others (stock, etc): None

The Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Sponsored by the National Heart, Lung, and Blood Institute (NHLBI) in Collaboration with the Department of Veterans Affairs (VA)

90% previously treated 10% untreated 42,418 high-risk hypertensive patients Chlorthalidone mg Amlodipine mg Lisinopril mg Doxazosin 1-8 mg N=15,255 N=9,048 N=9,054 N=9,061 Atenolol 28.0% Clonidine 10.6% Reserpine 4.3% Hydralazine 10.9% Hypertension Trial ALLHAT STEP 2 AND 3 AGENTS STEP 1 AGENTS (Double-blind)

90% previously treated 10% untreated 42,418 high-risk hypertensive patients Chlorthalidone mg Amlodipine mg Lisinopril mg Doxazosin 1-8 mg N=15,255 N=9,048 N=9,054 N=9,061 STEP 2 AND 3 AGENTS Atenolol 28.0% Clonidine 10.6% Reserpine 4.3% Hydralazine 10.9% Hypertension Trial ALLHAT STEP 1 AGENTS (Double-blind)

Inclusion Criteria Men and women aged > 55 years Men and women aged > 55 years Seated blood pressure (2 categories): Seated blood pressure (2 categories): 1) Treated least 2 months: BP <160/100 mm Hg 2) Not on drugs or on drugs < 2 months: SBP mm Hg or DBP mm Hg Additional risk factor or target organ damage. Additional risk factor or target organ damage. ALLHAT

Baseline Characteristics CALAll Sample Size 15,2559,0489,05433,357 Mean SBP/DBP 145 / 83 Mean age, years Black, % Women, % Current smoking % ASCVD, % Type II diabetes, % LVH by ECG, % 3333 Mean BMI, kg/m ALLHAT

Mean Systolic and Diastolic BP by Treatment Group Over Time Months of Follow-up mm Hg ALLHAT ~~~~ Systolic BP Diastolic BP Chlorthalidone Amlodipine Lisinopril

Percentage of Participants Receiving Blinded Study Drug or Same Class ALLHAT Chlorthalidone Amlodipine Lisinopril

Number of Antihypertensive Drugs Used and BP Control (<140/90 mm Hg) ALLHAT Chlorthalidone Amlodipine Lisinopril

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

Number of Antihypertensive Drugs Prescribed Months of Follow-Up Percent ALLHAT C C C AA A L L L

Percent Controlled (BP < 140/90) at Five Years by Number of Drugs Prescribed ALLHAT Chlorthalidone Amlodipine Lisinopril

Cumulative Percent Controlled (BP < 140/90) at Five Years by Number of Drugs Prescribed ALLHAT Chlorthalidone Amlodipine Lisinopril

Number of Drugs Needed to Control BP (<140/90 mm Hg) in ALLHAT After 5 Years 26% of participants were controlled on 1 drug (another 2% were untreated):26% of participants were controlled on 1 drug (another 2% were untreated):  therefore, at least 72% received or needed ≥ 2 drugs. 49% were controlled on 1 or 2 drugs (12% more were uncontrolled on 1 drug or untreated):49% were controlled on 1 or 2 drugs (12% more were uncontrolled on 1 drug or untreated):  therefore, at least 39% received or would have needed ≥ 3 drugs to control BP. 60% were controlled on 3 or fewer drugs:60% were controlled on 3 or fewer drugs:  therefore, at least 16% received or needed ≥ 4 drugs to control BP. ALLHAT

Conclusions - 1 BP was well controlled in the majority of participants in ALLHAT. BP was well controlled in the majority of participants in ALLHAT. Average BP was well below 140/90 mm Hg for participants in each randomized group. Average BP was well below 140/90 mm Hg for participants in each randomized group. More participants were controlled with chlorthalidone than the other two agents as monotherapy. More participants were controlled with chlorthalidone than the other two agents as monotherapy. ALLHAT

However, <30% of participants could be controlled on any of the drugs as a single agent. However, <30% of participants could be controlled on any of the drugs as a single agent. At least 2 medications were required for most participants to achieve BP control. At least 2 medications were required for most participants to achieve BP control. These ALLHAT data support the recommendations of JNC 7 promoting multidrug regimens and the initial selection of thiazide-type diuretics for most patients to improve BP control rates. These ALLHAT data support the recommendations of JNC 7 promoting multidrug regimens and the initial selection of thiazide-type diuretics for most patients to improve BP control rates. Conclusions - 2 ALLHAT

BMI ≥ 30 kg/m 2 Factors Related to Blood Pressure Control at 36 Months of Follow-up Chlorthalidone Amlodipine ALLHAT Prior BP Treatment Smoker Type II Diabetic nonBlack Age Per Decade ↑ Baseline SBP (10 mm Hg ↑) Cr ≥ 1.5 mg/dL Male BP Control BP Control BP Control BP Control Worse Better Worse Better (0.78, 0.83) 0.93 (0.88, 0.98) 1.10 (1.02, 1.20) 1.28 (1.17, 1.39) 0.88 (0.81, 0.96) 1.03 (0.93, 1.14) 0.87 (0.80, 0.95) 0.69 (0.60, 0.80) 0.79 (0.67, 0.94) BP Control BP Control BP Control BP Control Worse Better Worse Better (0.78, 0.84) 0.91 (0.84, 0.98) 0.98 (0.88, 1.09) 1.56 (1.39, 1.74) 0.83 (0.74, 0.92) 0.96 (0.84, 1.09) 0.88 (0.79, 0.98) 0.66 (0.55, 0.81) 0.83 (0.65, 1.07)

Prior BP Treatment BMI ≥ 30 kg/m 2 Smoker Type II Diabetic nonBlack Age Per Decade ↑ Factors Related to Blood Pressure Control at 36 Months of Follow-up Chlorthalidone Lisinopril ALLHAT Baseline SBP (10 mm Hg ↑) Cr ≥ 1.5 mg/dL Male BP Control BP Control BP Control BP Control Worse Better Worse Better (0.78, 0.83) 0.93 (0.88, 0.98) 1.10 (1.02, 1.20) 1.28 (1.17, 1.39) 0.88 (0.81, 0.96) 1.03 (0.93, 1.14) 0.87 (0.80, 0.95) 0.69 (0.60, 0.80) 0.79 (0.67, 0.94) BP Control BP Control BP Control BP Control Worse Better Worse Better (0.75, 0.81) 0.89 (0.83, 0.96) 1.19 (1.07, 1.33) 1.56 (1.39, 1.75) 0.89 (0.80, 1.00) 0.93 (0.81, 1.06) 0.91 (0.81, 1.01) 0.62 (0.51, 0.75) 0.91 (0.72, 1.15)

Multiple Logistic Regression Analysis: Relative Odds (95% CI) of BP Control at 36 Months ALLHAT BP Control Better Age (10 year ↑)  Baseline SBP (10 mmHg ↑) * Male * Black  Type 2 Diabetic Smoker  ASCVD * BMI ≥ 30 kg/m 2 * Prior Rx * Cr ≥ 1.5 mg/dL * ECG LVH * Clinic Research Exp. * BP Control Worse More ( * ) or less (  ) likely to be on 2+ drugs Cushman, et al. J Clinical Hypertens 2002; 4:

Logistic Regression Analysis of Relative Odds (95% CI) of Being On 2+ Drugs at 36 Months ALLHAT Age (10 year ↑) Black Smoker Prior Rx More Likely To Be On 2+ Drugs Baseline SBP (10 mmHg ↑) Male Type 2 Diabetic ASCVD BMI ≥ 30 kg/m2 Cr ≥ 1.5 mg/dL ECG LVH Clinic Research Exp. Less Likely To Be On 2+ Drugs Cushman, et al. J Clinical Hypertens 2002; 4:

BP Control (<140/90 mm Hg) by Randomized Group and Race Black Non-Black

Number of Drugs Needed to Control BP (<140/90 mm Hg) in ALLHAT After 5 Years ALLHAT No. of Drugs Chlorthalidone N = 5670 Amlodipine N = 3400 Lisinopril N = 3191 ALL N = 12,261 <140/90≥140/90<140/90≥140/90<140/90≥140/90<140/90≥140/ or Total