What first‑line antihypertensive regimen should be started in an African‑American adult with stage 2 hypertension (blood pressure 150/100 mmHg)?

First-Line Antihypertensive Therapy for African Americans with Stage 2 Hypertension (BP 150/100 mmHg)

Start immediately with a two-drug combination of chlorthalidone 12.5–25 mg daily plus amlodipine 5–10 mg daily, preferably as a single-pill formulation, to achieve a target blood pressure <130/80 mmHg. 1, 2, 3

Why Combination Therapy Is Mandatory at This Blood Pressure Level

• Your patient has stage 2 hypertension (≥140/90 mmHg) and is >20/10 mmHg above the <130/80 mmHg target, which mandates starting with two drugs from different first-line classes rather than monotherapy. 1, 2, 3

• 50–60% of African American patients fail to achieve BP <130/80 mmHg with monotherapy alone, making early combination therapy the evidence-based standard rather than sequential monotherapy. 1, 2

• Single-pill combinations dramatically improve medication adherence and persistence compared with separate pills, which is critical for long-term cardiovascular protection. 1, 3

Why Chlorthalidone + Amlodipine Is the Optimal Regimen

Chlorthalidone as the Preferred Thiazide

• Chlorthalidone 12.5–25 mg daily is the single best-evidenced first-line agent for African Americans, providing superior cardiovascular outcomes in the ALLHAT trial of >50,000 participants—including substantial Black representation—where it reduced heart failure by 38% versus amlodipine and stroke by 15% versus lisinopril. 1, 2, 4

• Chlorthalidone has a 40–60 hour half-life that delivers true 24-hour BP control, unlike hydrochlorothiazide, and has the most robust cardiovascular risk-reduction data of any antihypertensive class. 1, 2, 4

• The 2010 International Society on Hypertension in Blacks consensus statement—which proved prescient—designated chlorthalidone as the preferred thiazide diuretic years before other guidelines followed suit. 4

Amlodipine as the Preferred Calcium-Channel Blocker

• Amlodipine 5–10 mg daily achieves BP lowering and cardiovascular protection comparable to chlorthalidone in African Americans and is more effective than ACE inhibitors for stroke prevention in this population. 1, 2

• Amlodipine is weight-neutral and does not worsen lipid or glucose profiles, avoiding the metabolic adverse effects (dyslipidemia, insulin resistance) that thiazides can cause—an important consideration if your patient has obesity or metabolic syndrome. 1

• The combination of a thiazide diuretic plus a calcium-channel blocker produces BP reductions in Black patients that are comparable to those in other racial groups, making this the most effective two-drug regimen. 1, 2

Why ACE Inhibitors and ARBs Should NOT Be Used as Initial Therapy

• ACE inhibitors and ARBs are 30–36% less effective than thiazides or calcium-channel blockers for stroke prevention and BP reduction in African Americans because of lower renin activity in this population. 1, 2, 4

• In the ALLHAT trial, lisinopril was significantly inferior to chlorthalidone for preventing stroke and heart failure in Black patients. 1, 2

• Black patients have a 3–4 times higher risk of ACE-inhibitor-induced angioedema compared with other racial groups, making these agents less safe as well as less effective. 1, 2

• Reserve ACE inhibitors or ARBs for compelling indications only (diabetes with nephropathy, chronic kidney disease with proteinuria, heart failure with reduced ejection fraction) or add them as a third agent if BP remains uncontrolled on thiazide + CCB. 1, 2, 4

Target Blood Pressure and Monitoring Schedule

• Target BP is <130/80 mmHg for all African American adults with hypertension, regardless of age or comorbidities, based on ACC/AHA 2017 guidelines. 1, 2, 3

• The 2010 International Society on Hypertension in Blacks recommended even lower targets (<135/85 mmHg for primary prevention, <130/80 mmHg for secondary prevention), which were considered aggressive at the time but are now standard. 4, 5

• Follow up monthly after initiating therapy until the BP target is achieved, then every 3–5 months for maintenance. 1, 3

• Obtain baseline labs (creatinine, eGFR, potassium, sodium, fasting glucose, lipids) before starting therapy, then repeat creatinine, eGFR, and potassium within 1–2 weeks to detect hypokalemia or changes in renal function. 1, 3

When to Escalate to Triple Therapy

• If BP remains ≥130/80 mmHg after 4 weeks on chlorthalidone 25 mg + amlodipine 10 mg, add an ACE inhibitor or ARB as the third agent (e.g., lisinopril 10–40 mg daily or losartan 50–100 mg daily). 1, 2, 3

• The triple combination of thiazide + CCB + ACE inhibitor/ARB addresses three distinct pathophysiologic mechanisms (volume reduction, peripheral vasodilation, RAS inhibition) and is the standard escalation pathway. 1, 3

• If BP remains uncontrolled on triple therapy, add spironolactone 25–50 mg daily as the fourth agent for resistant hypertension. 1, 3

Critical Pitfalls to Avoid

• Do not start with ACE-inhibitor or ARB monotherapy in African Americans without a compelling indication (diabetes with nephropathy, CKD with proteinuria, heart failure); this is the single most common prescribing error and results in inferior stroke and heart-failure prevention. 1, 2, 4

• Do not use hydrochlorothiazide at doses <25 mg daily; lower doses lack proven outcome benefit and are less effective than chlorthalidone. 1, 2

• Do not delay combination therapy by starting with monotherapy and "stepping up" over months; your patient is already 20/10 mmHg above target and requires immediate two-drug therapy to reduce cardiovascular risk. 1, 3

• Do not use beta-blockers as first-line therapy unless there is a compelling indication (prior MI, heart failure with reduced ejection fraction); beta-blockers are approximately 36% less effective than CCBs and 30% less effective than thiazides for stroke prevention. 1, 2, 3

• Do not combine an ACE inhibitor with an ARB; dual RAS blockade increases hyperkalemia and acute kidney injury without added cardiovascular benefit. 1, 3

Lifestyle Modifications (Mandatory Adjunctive Therapy)

• Initiate comprehensive lifestyle changes immediately alongside pharmacologic therapy: sodium restriction to <2.3 g/day, increased dietary potassium (3,500–5,000 mg/day), weight management if overweight (target BMI <25 kg/m²), regular aerobic exercise (90–150 minutes/week), and limited alcohol intake (≤2 drinks/day for men, ≤1 drink/day for women). 1, 3

• These non-pharmacologic measures are particularly effective in African Americans and provide additive benefits to antihypertensive medications, potentially allowing dose reduction once BP is controlled. 1, 4