What is the first-line treatment for an adult patient with primary hypertension?

First-Line Treatment for Primary Hypertension in Adults

For most adults with primary hypertension, initiate treatment with a thiazide or thiazide-like diuretic (particularly chlorthalidone 12.5-25 mg daily), as this drug class demonstrates the strongest evidence for reducing cardiovascular mortality, stroke, and heart failure compared to other first-line agents. 1, 2, 3

Treatment Initiation Strategy Based on Blood Pressure Stage

Stage 1 Hypertension (130-139/80-89 mmHg)

• Start with single-agent monotherapy and titrate the dosage upward before adding a second agent 4, 1, 2
• Patients with 10-year ASCVD risk ≥10% should receive pharmacotherapy immediately combined with lifestyle modifications 4
• Patients with 10-year ASCVD risk <10% should attempt lifestyle modifications alone for 3-6 months before initiating pharmacotherapy 4

Stage 2 Hypertension (≥140/90 mmHg)

• Initiate with two-drug combination therapy from different first-line classes, preferably as a single-pill combination to improve adherence 4, 1, 2
• Effective combinations include: ACE inhibitor/ARB + calcium channel blocker, ACE inhibitor/ARB + thiazide diuretic, or calcium channel blocker + thiazide diuretic 2, 5

First-Line Drug Class Options

The four evidence-based first-line classes are thiazide/thiazide-like diuretics, ACE inhibitors, ARBs, and long-acting dihydropyridine calcium channel blockers 1, 6, 7. However, thiazide diuretics, particularly chlorthalidone, provide optimal first-step therapy based on the strongest evidence from meta-analyses and large randomized controlled trials 1, 2, 3.

Why Chlorthalidone is Preferred

• The ALLHAT trial demonstrated chlorthalidone's superiority over ACE inhibitors for stroke prevention and superiority over calcium channel blockers for heart failure prevention 2, 8
• Chlorthalidone has been evaluated in over 50,000 patients across three major comparative trials versus placebo, ACE inhibitors, and calcium channel blockers 8
• When chlorthalidone is unavailable, hydrochlorothiazide (possibly combined with amiloride or triamterene) is a reasonable alternative 8

Alternative First-Line Agents

• Long-acting dihydropyridine calcium channel blockers (amlodipine 5-10 mg daily) are equally effective as thiazides for all cardiovascular events except heart failure 2
• ACE inhibitors (lisinopril 10-40 mg daily) or ARBs (losartan 50-100 mg daily) are equally effective alternatives, particularly for patients with albuminuria or established coronary artery disease 1, 2, 9

Special Population Considerations

Black Patients Without Heart Failure or CKD

• Start with a thiazide diuretic or calcium channel blocker 1, 2, 5
• Avoid ACE inhibitors or ARBs as monotherapy, as these have smaller blood pressure effects in Black patients 2, 9

Patients with Diabetes

• All four first-line classes are equally effective 2, 5
• If microalbuminuria or proteinuria is present, prefer ACE inhibitor or ARB as first-line therapy 4, 1, 2, 5
• Target blood pressure is <130/80 mmHg 4

Patients with Chronic Kidney Disease or Proteinuria

• ACE inhibitor or ARB is mandatory first-line therapy to reduce progressive kidney disease 1, 2, 5
• Add a thiazide diuretic or calcium channel blocker as second agent 2, 5

Patients with Heart Failure with Reduced Ejection Fraction

• Do not use standard hypertension first-line approach; instead, initiate with a beta blocker plus ACE inhibitor or ARB, followed by mineralocorticoid receptor antagonist and diuretic based on volume status 4, 5

Blood Pressure Targets

• General population: <140/90 mmHg (strong recommendation) 1, 2
• Adults <65 years: <130/80 mmHg 1, 2
• Patients with known CVD or 10-year ASCVD risk ≥10%: <130/80 mmHg (strong recommendation) 4, 1, 2, 6
• Adults ≥65 years: SBP <130 mmHg 6

Critical Contraindications and Pitfalls

• Never combine ACE inhibitor + ARB + renin inhibitor simultaneously, as this is potentially harmful without additional benefit 4, 3
• Beta-blockers are not recommended as first-line unless the patient has ischemic heart disease or heart failure 3
• Alpha-blockers are less effective than thiazide diuretics for cardiovascular disease prevention 3
• Nondihydropyridine calcium channel blockers (verapamil, diltiazem) are not recommended in patients with heart failure with reduced ejection fraction due to myocardial depressant activity 4

Monitoring Schedule

• Monthly follow-up after initiating or changing medications until target blood pressure is achieved 1, 2, 3
• Every 3-5 months once blood pressure is controlled 1, 2, 3
• Monitor renal function and potassium within 7-14 days when starting ACE inhibitors, ARBs, or diuretics, then at least annually 2
• Check standing blood pressure in elderly patients to assess for orthostatic hypotension 2

Practical Dosing Recommendations

• Chlorthalidone: 12.5-25 mg once daily 2, 8
• Amlodipine: 5-10 mg once daily 2
• Lisinopril: 10-40 mg once daily 2, 9
• Losartan: 50-100 mg once daily 2, 10