Blood Pressure Control in Hispanics in the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Karen L. Margolis, Linda B. Piller, Charles E. Ford, Mario Henriquez, William C. Cushman, Paula T. Einhorn, Pedro J. Colon, Sr., Donald G. Vidt, Rudell Christian, Nathan D. Wong, Jackson T. Wright, Jr., David C. Goff, Jr., for the ALLHAT Collaborative Research Group Hypertension. 2007;50: ALLHAT

Population With Hypertension (%) From Bernard Cheung Ong, et al, Hypertension 2007 Prevalence of Hypertension in U.S. by Race/Ethnicity:

Hypertension Awareness, Treatment and Control White Non- Hispanic Mexican American NHANES II NHANES III Hisp HANES NHANES III Aware Treat Control

Changes in Hypertension Awareness, Treatment, and Control NHANES – some improvement among Mexican-Americans, but disparities remain BP Control Total Among Treated Hypertensives Mexican American27%57% Non-Hispanic Black29%52% Non-Hispanic White35%68%

Reasons for Racial and Ethnic Differences in BP Control? Lack of access to health care Inability to afford medication Other socioeconomic factors Beliefs about hypertension Language barriers Poor MD-patient communication Family influences Diet Metabolic risk factors Other biological factors  insufficient treatment or resistance to treatment

6 Antihypertensive Trial Design Randomized, double-blind, concurrently controlled practice-based clinical trial in 42,418 participants with hypertension comparing 4 commonly-used antihypertensive drugs. ALLHAT investigated whether there was a difference in fatal CHD & nonfatal MI (primary endpoint) among patients randomized to CCB, ACEI, or alpha-blocker compared to a thiazide-type diuretic. Step-up medications as needed for BP control. ALLHAT

Secondary Outcomes All-cause mortality Stroke Combined CHD – nonfatal MI, CHD death, coronary revascularization, hospitalized angina Combined CVD – combined CHD, stroke, lower extremity revascularization, other treated angina, treated HF Other – renal (reciprocal serum creatinine, ESRD, estimated GFR), diabetes, and cancer ALLHAT

Inclusion Criteria Men and women aged > 55 years Seated blood pressure (2 categories): 1) Treated least 2 months (1-2 drugs). 2) Not on drugs or on drugs <2 months. Additional risk factor or target organ damage. ALLHAT

BP Eligibility Criteria ALLHAT

10 Doxazosin Arm Terminated Early Statistically significant 25% higher rate of major secondary endpoint, combined CVD outcomes (2-fold higher rate of heart failure and 20% higher risk of stroke) Futility of finding a significant difference for primary CHD outcome ALLHAT JAMA. 2000; & Hypertension. 2003;42:

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

42,418 participants randomized (Feb through Jan. 1998) After excluding doxazosin arm – 33,357 – – 3% Black Hispanic (BH) – – 16% White Hispanic (WH) – – 33% Black nonHispanic (BNH) – – 48% White nonHispanic (WNH) 73% of Hispanics were from Puerto Rico Study Population ALLHAT

Treatment Access to high-quality hypertension care Study medications at no cost Required dosage titration and additional medications if SBP  140 or DBP  90 mmHg. ALLHAT

Antihypertensive Treatment Regimen Step 1Dose 1Dose 2Dose 3 Chlorthalidone12.5 mg 25 mg Amlodipine2.5 mg5 mg10 mg Lisinopril10 mg20 mg40 mg Step 2 Reserpine0.05 mg qd0.1 mg qd0.2 mg qd Clonidine0.1 mg bid0.2 mg bid0.3 mg bid Atenolol25 mg qd50 mg qd100 mg qd Step 3 Hydralazine25 mg bid50 mg bid100 mg bid ALLHAT

Baseline Characteristics-1 ALLHAT BHWHBNHWNH Sample Size 1,0905,23910,60815,705 Mean SBP/DBP 147/87146/85145/84145/82 Previous HT treatment, % Mean age, years Women, % Current smoking, % History of type II diabetes, % ASCVD, % LVH by baseline ECG, % 3262

Baseline Characteristics-2 ALLHAT BHWHBNHWNH Sample Size 1,0905,23910,60815,705 Puerto Rican or USVI, % Education, years Mean BMI, kg/m S. Creatinine, mg/dL F. Glucose, mg/dL

Mean Systolic Blood Pressure by Race and Ethnicity ALLHAT

Mean Diastolic Blood Pressure by Race and Ethnicity ALLHAT

Blood Pressure Control ALLHAT

Number of Antihypertensive Medications ALLHAT

Participants with Uncontrolled BP on 1 Medication – Percentage Stepped Up ALLHAT

Participants with Uncontrolled BP on 2 Medications – Percentage Stepped Up ALLHAT

Relative Odds of BP Control at Year 2 UnadjustedAdjusted* OR†95% CIOR†95% CI Total Black Hisp – – 1.25 White Hisp – – 1.31 Black nonHisp – – 0.78 Excluding PR/VI Black Hisp – – 1.52 White Hisp – – 1.22 Black nonHisp – – 0.78 * Adjusted for age, sex, race-ethnicity, history of diabetes, current smoking, history of ASCVD, BMI  30 kg/m 2, antihypertensive treatment prior to enrollment, baseline SBP, creatinine  1.5 mg/dL, LVH on ECG, treatment assignment. † Compared with White non-Hispanic ALLHAT

Summary - 1 U.S. population 14.1% Hispanic/Latino in 2004 Hispanic ALLHAT participants had equivalent or superior BP control compared with non- Hispanics – – Equal access to care – – No-cost medications Also reported in INVEST Hispanic Blacks had slightly lower levels of BP control compared with Hispanic whites, similar BP control to non-Hispanic whites, and better BP control than non-Hispanic Blacks. ALLHAT

Summary - 2 Compared with non-Hispanic whites, Hispanics less likely to have health insurance or regular source of care, less likely to receive preventive services – – Linked to lower rates of BP screening and treatment in Hispanics Primary care clinics in Boston – Hispanic participants less likely to have meds intensified, but if intensified, equally likely to achieve BP control THUS: Hispanic patients likely to face barriers to hypertension screening, initiation of therapy, and appropriate intensification of therapy. ALLHAT

Conclusions Low rate of BP control in US Hispanics not due to biological factors. – – Controlled in  2/3 of Hispanic ALLHAT participants – – Commonly-available medications, including thiazide-type diuretics Focus on improving: – – Hypertension knowledge and awareness – – Doctor-patient communication – – Access to medical care – – Affordable medications BP control in Hispanic patients is an achievable goal and should therefore be declared a public health priority ALLHAT

Reserve Slide

Summary - 3 Other explanations for better BP control among Hispanic participants? Adherence to med may have been lower among Hispanics prior to randomization (slightly higher BP levels) – more Hispanics essentially “untreated”? Systematic bias in BP measurements – – 0 terminal digit preference associated with underestimates of BP, undertreatment of hypertension – – Relatively high frequency (24% for SBP at 1 year) – 42% in Hispanics vs 21% in non-Hispanics) – especially high in PR and USVI – – No evidence for systematic effort to inflate BP control rates ALLHAT

Clinical Inertia Failure to advance therapy despite suboptimal BP control Reinforces need for effective methods to improve BP control through comprehensive programs – – Patients – – Providers – – Health care systems ALLHAT