1. Success and Predictors of Blood Pressure Control in Diverse North American Settings: The Antihypertensive and Lipid- lowering Treatment to Prevent Heart Attack Trial (ALLHAT) William C Cushman, MD, Charles E Ford, PhD, Jeffrey A Cutler, MD, Karen L Margolis, MD, MPH, Barry R Davis, MD, PhD, et al, for the ALLHAT Collaborative Research Group J Clinical Hypertens 2002; 4:393-404 ALLHAT

3. NHANES III: NHANES III:  27% for adults with hypertension.  Among those on treatment in NHANES III: 30 to 45% in older adults from various sex- race/ethnicity groups. In treated patients in Olmstead County, MN: In treated patients in Olmstead County, MN:  33% among persons 45 years and older. At a group of New England Veterans Affairs Medical Centers: At a group of New England Veterans Affairs Medical Centers:  < 25% in older (mostly white) males Blood Pressure Control (<140/90 mm Hg) Rates in The United States in the 1990s Burt, et al. Hypertension 1995;25:305-13. Meissner, et al. Hypertension 1999;34:466-71. Berlowitz, et alN Engl J Med 1998;339:1957-63.

4. 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

5. 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 for @ least 2 months. 2) Not on drugs or on drugs < 2 months. Additional risk factor or target organ damage. Additional risk factor or target organ damage. ALLHAT

6. ALLHAT BP Eligibility Criteria ALLHAT

7. Baseline Characteristics Sample Size 33,357 Mean SBP/DBP 145 / 83 Mean age, years 67 Black, % 35 Women, % 47 Current smoking % 22 ASCVD, % 47 Type II diabetes, % 36 LVH by ECG, % 3 Mean BMI, kg/m 2 30 ALLHAT

8. Baseline Characteristics Serum Creatinine, mg/dL 1.02 Fasting Glucose, mg/dL 125 Total Cholesterol, mg/dL 216 LDL-Cholesterol, mg/dL 136 HDL-Cholesterol, mg/dL 47 Triglycerides, mg/dL 172 ALLHAT

9. Antihypertensive Treatment Regimen Step 1 Dose 1 Dose 2 Dose 3 Chlorthalidone 12.5 mg 25 mg Amlodipine 2.5 mg 5 mg 10 mg Lisinopril 20 mg 40 mg Step 2 Reserpine 0.05 mg qd 0.1 mg qd 0.2 mg qd Clonidine 0.1 mg bid 0.2 mg bid 0.3 mg bid Atenolol 25 mg qd 50 mg qd 100 mg qd Step 3 Hydralazine 25 mg bid 50 mg bid 100 mg bid ALLHAT

10. Mean Systolic and Diastolic Blood Pressure Months of Follow-up mm Hg ALLHAT 70 75 80 85 90 135 140 145 150 ~~~~ Systolic BP Diastolic BP Cushman, et al. J Clinical Hypertens 2002; 4:393-404

11. BP Results by Treatment Group Compared to chlorthalidone: SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg). Compared to chlorthalidone: DBP significantly lower in the amlodipine group (~1 mm Hg). ALLHAT JAMA 2002;288:2981-2997 BL6M1Y3Y5YC146.2138.2136.6134.6134.1 A146.2140.0138.3135.4134.9 L146.4141.4139.7136.4136.1 BL6M1Y3Y5YC84.080.179.277.175.4 A83.979.778.576.174.5 L84.180.879.777.275.4

12. SBP Distribution at Baseline and 36 Months of Follow-up Baseline: 31% < 140 mm Hg 14%  160 mm Hg 36 Months: 64% < 140 mm Hg 8%  160 mm Hg 8%  160 mm Hg SBP (mm Hg) Percent ALLHAT Cushman, et al. J Clinical Hypertens 2002; 4:393-404

13. DBP Distribution at Baseline and 36 Months of Follow-up Baseline 68% < 90 mm Hg 4% ≥ 100 mm Hg 4% ≥ 100 mm Hg 36 Months 90% < 90 mm Hg 2% ≥ 100 mm Hg 2% ≥ 100 mm Hg DBP (mm Hg) Percent ALLHAT Cushman, et al. J Clinical Hypertens 2002; 4:393-404

14. Blood Pressure Control ALLHAT Cushman, et al. J Clinical Hypertens 2002; 4:393-404 Blood Pressure Control

15. SBP Distribution at 36 Months of Follow-up 64% < 140 mm Hg 36%  140 mm Hg 8%  160 mm Hg 8%  160 mm Hg Of those  140 mm Hg: 53% 140-149 mm Hg 24% 150-159 mm Hg (77% 140-159 mm Hg) SBP (mm Hg) Percent ALLHAT Cushman, et al. J Clinical Hypertens 2002; 4:393-404

16. BP Control (<140/90 mm Hg) at 5 Years by Randomized Group JAMA 2002;288:2981-2997

17. Blood Pressure Control ALLHAT 1.4 1.6 1.7 1.8 2.0 1.6 = mean number of drugs Cushman, et al. J Clinical Hypertens 2002; 4:393-404

18. Use of Blinded (Step 1) Drug and Number of Antihypertensive Drugs Prescribed Months of Follow-Up Percent ALLHAT On Step 1 Drug On 1 Drug On 2 Drugs On 3 Drugs On 4+ Drugs @ 5 years:62% were on >2 drugs, 30% were on 1 drug with BP 2 drugs, 30% were on 1 drug with BP <140/90 mm Hg Cushman, et al. J Clinical Hypertens 2002; 4:393-404

19. Proportion of Uncontrolled ALLHAT Participants Not Stepped Up at Annual Visits Cushman, et al. J Clinical Hypertens 2002; 4:393-404

20. Multiple Logistic Regression Analysis: Relative Odds (95% CI) of BP Control at 36 Months ALLHAT BP Control Better 0.50.60.70.80.911.11.2 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; 4:393-404

21. Logistic Regression Analysis of Relative Odds (95% CI) of Being On 2+ Drugs at 36 Months ALLHAT Age (10 year ↑) Black Smoker Prior Rx 0.70.91.11.31.51.71.92.12.3 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; 4:393-404

22. Relative Odds (95% CI) of BP Control or Being On 2+ Drugs at 36 Months of Follow-Up, by Geographic Region (Compared with West) ALLHAT 0.20.40.60.811.21.41.61.82 More Likely To Be On 2+ Drugs Midwest East South Canada Puerto Rico/VI East South Canada PuertoRico/VI Midwest Less Likely To Be On 2+ Drugs BP Control Better BP Control Worse Cushman, et al. J Clinical Hypertens 2002; 4:393-404

23. Other Large Trials and BP Control LIFE (4.8 years of f/u): LIFE (4.8 years of f/u):  46%: atenolol arm  49%: losartan arm CONVINCE (30 and 36 months of f/u): CONVINCE (30 and 36 months of f/u):  67% overall and similar in verapamil HS and standard therapy arms

24. Conclusions - 1 The ALLHAT trial provides compelling evidence that BP control rates can be markedly increased to at least 2/3 of the treated hypertensive population. The ALLHAT trial provides compelling evidence that BP control rates can be markedly increased to at least 2/3 of the treated hypertensive population. These control rates were achieved in a multiethnic hypertensive population in diverse practice settings. These control rates were achieved in a multiethnic hypertensive population in diverse practice settings. Most of the participants who did not achieve goal had persistent elevation of SBP. Most of the participants who did not achieve goal had persistent elevation of SBP. ALLHAT

25. At least 2 antihypertensive medications are required for most patients to achieve BP control. At least 2 antihypertensive medications are required for most patients to achieve BP control. Various factors that are associated with lower BP control rates were identified. Various factors that are associated with lower BP control rates were identified. It is likely that the majority of people with hypertension could achieve BP < 140/90 mm Hg with the antihypertensive medications available today. It is likely that the majority of people with hypertension could achieve BP < 140/90 mm Hg with the antihypertensive medications available today. ALLHAT Conclusions - 2

26. 26 BP Inadequately Controlled † in Nearly 75% of Adult Hypertensives * in the US 68%54%27% †SBP <140 mm Hg and DBP <90 mm Hg. NHANES = National Health and Nutrition Examination Surveys. Age 18 to 74 years with SBP 140 mm Hg or DBP 90 mm Hg or taking antihypertensive medication.Age 18 to 74 years with SBP 140 mm Hg or DBP 90 mm Hg or taking antihypertensive medication. JNC VI. Arch Intern Med. 1997;157:2413-46. NHANES III (Phase 2) 1991-1994 NHANES III (Phase 1) 1988-1991 73%55%29% NHANES II 1976-1980 51%31%10%AwareTreated Controlled †

27. Participants were randomized to chlorthalidone (15,255), amlodipine (9,048), lisinopril (9,054), or doxazosin (9,061) between 2/94-1/98. [Sponsored by NHLBI]Participants were randomized to chlorthalidone (15,255), amlodipine (9,048), lisinopril (9,054), or doxazosin (9,061) between 2/94-1/98. [Sponsored by NHLBI] Over 15,000 (>3000/drug group) of ALLHAT participants had DM at baseline and a similar # were African Americans.Over 15,000 (>3000/drug group) of ALLHAT participants had DM at baseline and a similar # were African Americans. The doxazosin arm was stopped in January 2000 due to higher CV events and virtually no chance to show a difference in CHD.The doxazosin arm was stopped in January 2000 due to higher CV events and virtually no chance to show a difference in CHD. The remaining 3 arms continued to scheduled completion and were reported in December 2002.The remaining 3 arms continued to scheduled completion and were reported in December 2002. ALLHAT n=42,418 ALLHAT

28. Inclusion Criteria - 2 At least one of the following: Myocardial infarction or stroke: age-indeterminate or at least 6 months old Myocardial infarction or stroke: age-indeterminate or at least 6 months old History of revascularization procedure History of revascularization procedure Other documented ASCVD Other documented ASCVD Major ST segment depression or T-wave inversion Major ST segment depression or T-wave inversion Type II diabetes mellitus Type II diabetes mellitus HDL cholesterol < 35 mg/dl on any 2 or more determinations in past 5 years HDL cholesterol < 35 mg/dl on any 2 or more determinations in past 5 years Left ventricular hypertrophy (past 2 years) on ECG or echo Left ventricular hypertrophy (past 2 years) on ECG or echo Current cigarette smoking Current cigarette smoking ALLHAT

29. Exclusion Criteria for Antihypertensive Trial Angina pectoris or recent MI or Stroke (within past 6 months) Angina pectoris or recent MI or Stroke (within past 6 months) Heart failure and/or LVEF < 35%, if known Heart failure and/or LVEF < 35%, if known Renal insufficiency (serum creatinine > 2.0 mg/dL) Renal insufficiency (serum creatinine > 2.0 mg/dL) Requiring diuretics, calcium channel blockers, ACE inhibitors, or alpha adrenergic blockers for reasons other than high blood pressure Requiring diuretics, calcium channel blockers, ACE inhibitors, or alpha adrenergic blockers for reasons other than high blood pressure Requiring more than two antihypertensive agents to achieve blood pressure control Requiring more than two antihypertensive agents to achieve blood pressure control Factors suggesting inability to comply with protocol Factors suggesting inability to comply with protocol ALLHAT

30. Number of Antihypertensive Drugs Used and BP Control (<140/90 mm Hg) ALLHAT 66% 27% 50% 55% 58% 62% 65% Cushman, et al. J Clinical Hypertens 2002; 4:393-404