Medical Education Library

MODULE 3: Using Thiazide-Type Diuretics in African Americans with Hypertension

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Dr Wright is a paid consultant to The Medical Letter, Inc, and Takeda Pharmaceuticals International, Inc. He is on an advisory board of Medtronic, Inc.


Hypertension and hypertensive target organ damage are more prevalent and more severe in certain minority populations, especially African Americans. Hypertension is more common, more severe, develops at an earlier age, and leads to greater morbidity and mortality in African Americans than in age-matched non-Hispanic whites.1 African Americans have among the highest rates of hypertension in the world (41% overall, 44% among black women) and develop the condition an average of 5 years earlier than whites.1

A recent report found that although treatment rates between whites and African Americans overall are similar, a smaller percentage of African Americans with hypertension are controlled to <140/90 mm Hg compared with whites.2 This may at least partly explain the 4 to 5 times higher hypertension-related mortality, 2 to 4 times increased risk of left ventricular hypertrophy (LVH), coronary heart disease (CHD), congestive heart failure, and stroke, and the 4 times higher rate of end-stage renal disease (ESRD) in African Americans compared with whites.1,3 The higher prevalence of diabetes mellitus, cigarette smoking, obesity, lipid disorders, and LVH in blacks exacerbates the existing risk posed by hypertension, making the need for aggressive blood pressure (BP) control even more critical.1

Antihypertensive treatment in African Americans

Lifestyle modification is recommended for all hypertensive patients but is especially important for African Americans. This population has a greater prevalence of obesity than whites, so weight loss is critical.4 Further, African Americans tend to have a greater sensitivity to salt because of a combination of obesity, abnormalities in renal salt handling, and a tendency to consume a high salt/low potassium diet.3 African Americans have been shown to benefit at least as much as other subgroups with hypertension from reductions in dietary salt and improvements in diet quality, such as the Dietary Approaches to Stop Hypertension (DASH) diet.5-7

Several studies have documented the efficacy of diuretics in lowering BP in African Americans.3,8-10 In the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial (ALLHAT), treatment initiated with the thiazide-type diuretic (THZD) chlorthalidone (CTD) reduced systolic BP (SBP) by 4 mm Hg more than treatment based on the angiotensin-converting enzyme inhibitor (ACEI) lisinopril or the alpha-blocker doxazosin in black ALLHAT participants who were receiving similar background antihypertensive drug treatment.9,10 The greater BP lowering in the THZD arm was associated with a significantly reduced rate in 1 or more cardiovascular disease (CVD) outcomes. Other inhibitors of the renin-angiotensin system (eg, angiotensin-receptor blockers [ARBs], direct renin inhibitors, and beta-blockers) are similarly less effective in lowering BP in African Americans.3 In contrast, when the calcium channel blocker (CCB) amlodipine was compared with CTD in blacks or when CTD was compared with lisinopril or doxazosin in nonblacks, SBP reductions were only ~1 mm Hg.8,10

As a class, diuretics have been shown to decrease hypertension-related morbidity and mortality in both African Americans and whites.10-15 In fact, much of the evidence for the benefits of antihypertensive therapy in preventing hypertension-related morbidity and mortality was conducted with THZDs, with several of the relevant trials containing significant numbers of African American participants (TABLE).8,10,13-16


Outcomes of major clinical trials of diuretics in African Americans

Clinical trialRelative risk reduction (RRR) or hazard ratio (HR) by endpoint
VA Cooperative: HCTZ + RES + HYD vs placebo (RRR)13 0.46
HDFP: stepped therapy with CTD vs usual care (HR)140.76a
SHEP: CTD + atenolol vs placebo (HR)15 0.68a
ALLHAT: All African Americans (RRR)8,10
  AML vs CTD0.971.061.030.931.46a1.15
  DOX vs CTDN/A1.28a1.111.38a1.84a0.99
  LIS vs CTD1.061.19a1.15a1.40a1.30a1.29
ALLHAT: African Americans with diabetes and metabolic syndrome (RRR)16
  AML vs CTD1.021.14a1.091.011.501.50
  DOX vs CTD1.181.37a1.151.49a1.88a1.17
  LIS vs CTD0.961.24a1.19a1.37a1.49a1.70a
ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; AML, amlodipine; CHD, coronary heart disease; CTD, chlorthalidone; CVD, cardiovascular disease; DOX, doxazosin; ESRD, end-stage renal disease; HCTZ, hydrochlorothiazide; HDFP, Hypertension Detection and Follow-up Program; HF, heart failure; HYD, hydralazine; LIS, lisinopril; RES, reserpine; SHEP, Systolic Hypertension in the Elderly Program; VA, Veterans Administration
aP ≤0.05

In the Veterans Administration (VA) Cooperative Trial, African American men comprised 42% of participants, all of whom were randomized to a combination of hydrochlorothiazide, reserpine, and hydralazine, or to placebo.13 In the Hypertension Detection and Follow-Up Program (HDFP) trial, 44% of participants were African American. All participants were randomized to stepped therapy with CTD, reserpine, methyldopa, and hydralazine, or to usual community care.14 Both of these pioneering trials documented the benefit of a THZD-based regimen in lowering BP and improving clinical outcomes in African Americans with hypertension. The Systolic Hypertension in the Elderly Program (SHEP) trial, in which 14% of participants were African American, extended earlier results from the VA Cooperative and HDFP trials by demonstrating that, compared with placebo, active treatment with CTD and the beta-blocker atenolol produced clinical outcome reductions in African Americans and whites with isolated systolic hypertension as well as in those with elevated diastolic BP.15

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