What class of medication is most appropriate for initial antihypertensive therapy in an African-American woman with hypertension?

Initial Antihypertensive Therapy for African-American Women

For an African-American woman with hypertension, initial antihypertensive therapy should be either a thiazide-type diuretic (chlorthalidone 12.5-25 mg/day or hydrochlorothiazide 25-50 mg/day) or a calcium channel blocker (such as amlodipine), as these agents are more effective than renin-angiotensin system inhibitors or beta-blockers in lowering blood pressure and reducing cardiovascular events in this population. 1, 2

Evidence-Based First-Line Recommendations

Thiazide-Type Diuretics

• Thiazide-type diuretics are more effective in African Americans than ACE inhibitors or ARBs for both blood pressure reduction and cardiovascular disease event prevention 1, 2
• Chlorthalidone is the preferred thiazide diuretic due to more cardiovascular disease risk reduction data and a longer therapeutic half-life compared to hydrochlorothiazide 2
• The recommended dose is chlorthalidone 12.5-25 mg/day or hydrochlorothiazide 25-50 mg/day 2
• In the ALLHAT trial with over 15,000 Black patients, thiazide diuretics were superior to ACE inhibitors, with the ACE inhibitor group showing 40% greater risk of stroke, 32% greater risk of heart failure, and 19% greater risk of cardiovascular disease 1

Calcium Channel Blockers

• Calcium channel blockers are equally effective as thiazide diuretics in African Americans and more effective than ACE inhibitors 1, 2
• Amlodipine is as effective as chlorthalidone and more effective than lisinopril in reducing blood pressure, cardiovascular disease, and stroke events in African Americans 2
• CCBs reduce blood pressure across all patient groups regardless of race, sex, or age 3
• CCBs are particularly effective in Black patients, who typically have lower renin levels 4

When to Use Combination Therapy

Initial Combination Therapy Indications

• Most African-American patients will require two or more antihypertensive medications to achieve blood pressure control below 130/80 mm Hg 1, 2
• Start with combination therapy if blood pressure is >15/10 mm Hg above goal 2, 5
• A single-tablet combination including either a diuretic or CCB is particularly effective in achieving blood pressure control in African Americans 1, 2

Recommended Combinations

• For initial dual therapy: thiazide diuretic + CCB, or CCB + ARB (not ACE inhibitor due to angioedema risk) 1, 2
• If blood pressure remains uncontrolled, progress to triple therapy with CCB + thiazide diuretic + ARB/ACE inhibitor 2, 5
• The combination of an ACE inhibitor or ARB with a CCB or thiazide diuretic produces similar blood pressure lowering in African Americans as in other racial groups 1

Special Clinical Scenarios

Chronic Kidney Disease with Proteinuria

• ACE inhibitors or ARBs should be included as components of multidrug regimens in African Americans with CKD and proteinuria 1, 2
• However, these agents need not be the initial therapy unless blood pressure control is achieved with a single agent 1

Heart Failure

• Add beta-blockers to the regimen for African Americans with heart failure 1, 2

Coronary Heart Disease Post-MI

• Beta-blockers are recommended for patients who have had a myocardial infarction 1, 2

Critical Safety Considerations

ACE Inhibitor Caution

• African Americans have a 3- to 4-fold higher risk of angioedema with ACE inhibitors compared to other racial groups 1, 2
• African Americans also experience more cough attributed to ACE inhibitors 1
• This makes ARBs preferable over ACE inhibitors when renin-angiotensin system blockade is needed 5

Avoid Monotherapy with RAS Inhibitors

• ACE inhibitors and ARBs are less effective in lowering blood pressure in African Americans when used as monotherapy 1
• The racial differences in blood pressure lowering with these drugs are abolished when combined with a diuretic 1

Treatment Algorithm

1. Assess blood pressure elevation:

   • If <15/10 mm Hg above goal: Start with monotherapy (thiazide diuretic OR CCB) 2, 5
   • If ≥15/10 mm Hg above goal: Start with dual combination therapy 2, 5

2. Initial monotherapy choice:

   • Chlorthalidone 12.5-25 mg/day (preferred thiazide) OR
   • Amlodipine 5-10 mg/day 2

3. Initial dual therapy choice:

   • CCB + thiazide diuretic OR
   • CCB + ARB (preferred over ACE inhibitor) 2, 5

4. If blood pressure remains uncontrolled after 3 months:

   • Increase to full doses 5
   • Add third agent: CCB + thiazide diuretic + ARB 2, 5

5. For resistant hypertension (uncontrolled on triple therapy):

   • Add spironolactone or other agents (eplerenone, amiloride, doxazosin, or beta-blocker) 2
   • Consider referral to hypertension specialist 5

Target Blood Pressure

• Goal blood pressure is <130/80 mm Hg for most African-American women 5, 6
• Aim to achieve target within 3 months of initiating therapy 5