What is the recommended initial antihypertensive medication for a patient with hypertension?

Initial Antihypertensive Medication Selection

For most adults with hypertension, initial therapy should be a thiazide-type diuretic (preferably chlorthalidone 12.5-25 mg daily), an ACE inhibitor/ARB, or a long-acting calcium channel blocker, with specific selection based on patient race, comorbidities, and blood pressure severity. 1, 2

Blood Pressure Thresholds for Starting Medication

• Initiate pharmacotherapy immediately when confirmed blood pressure is ≥140/90 mm Hg 2
• For high-risk patients (existing cardiovascular disease, diabetes, chronic kidney disease, or target organ damage), start treatment at 130-139/80-89 mm Hg 2
• Begin with two medications if blood pressure is ≥150/90 mm Hg or stage 2 hypertension is present 2, 3

First-Line Medication Classes by Patient Population

General Adult Population (No Specific Comorbidities)

Choose from three equally effective first-line options: 1, 2, 4

• Thiazide-type diuretic: Chlorthalidone 12.5-25 mg daily (preferred over hydrochlorothiazide due to superior 24-hour blood pressure control and cardiovascular outcomes) 5, 6, 7
• ACE inhibitor or ARB: Lisinopril 10 mg daily (can titrate to 20-40 mg) or equivalent 8, 4
• Long-acting dihydropyridine calcium channel blocker: Amlodipine 5-10 mg daily 1, 4

Critical distinction on thiazide selection: Chlorthalidone demonstrates significantly greater 24-hour ambulatory blood pressure reduction compared to hydrochlorothiazide, particularly during nighttime hours (13.5 mm Hg vs 6.4 mm Hg systolic reduction), and has superior cardiovascular outcomes data from landmark trials. 5, 6, 7 Hydrochlorothiazide 12.5 mg monotherapy may convert sustained hypertension into masked hypertension due to its short duration of action. 7

Black Adults Without Heart Failure or Chronic Kidney Disease

Start with either: 1, 2

• Thiazide-type diuretic (chlorthalidone 12.5-25 mg or hydrochlorothiazide 25-50 mg daily) 1
• Calcium channel blocker (amlodipine 5-10 mg daily) 1

Rationale: These classes are more effective as monotherapy in black patients and superior for preventing clinical outcomes including stroke. 1 ACE inhibitors and ARBs are less effective as monotherapy in this population and carry higher risk of angioedema. 1 However, most black patients require two or more medications to achieve blood pressure targets <130/80 mm Hg. 1

Patients With Diabetes

Preferred initial agents: 1, 2

• ACE inhibitor or ARB if albuminuria present (UACR ≥30 mg/g) 1
• Any of the four first-line classes (thiazide diuretic, ACE inhibitor, ARB, or calcium channel blocker) if no albuminuria 1
• Avoid beta-blockers as first-line unless specific cardiac indication (prior MI, active angina, heart failure with reduced ejection fraction) 1

Patients With Chronic Kidney Disease or Albuminuria

Use ACE inhibitor or ARB as first-line therapy to slow progression of kidney disease 2

Patients With Coronary Artery Disease

ACE inhibitor or ARB recommended as first-line for established coronary disease 1

Patients With Thoracic Aortic Disease

Beta-blockers are the preferred antihypertensive agents in this specific population 1

Monotherapy vs. Combination Therapy Algorithm

Start With Single Agent If:

• Blood pressure 130-149/80-89 mm Hg 2, 3
• No high-risk features present 2

Start With Two Agents If:

• Blood pressure ≥150/90 mm Hg 2, 3
• Stage 2 hypertension present 2
• Use single-pill combination when possible to improve medication adherence 2, 3

Preferred two-drug combinations: 1, 3

• Thiazide diuretic + ACE inhibitor or ARB
• Calcium channel blocker + ACE inhibitor or ARB
• Calcium channel blocker + thiazide diuretic

Avoid combining: Beta-blockers with thiazide diuretics as initial therapy due to increased adverse metabolic effects (dyslipidemia, glucose intolerance, weight gain difficulty) 1, 3

Dosing Strategy

Start at appropriate initial dose, then titrate upward: 2

• Lisinopril: Start 10 mg daily, titrate to 20-40 mg (maximum 80 mg, though doses above 40 mg show minimal additional benefit) 8
• Chlorthalidone: Start 12.5 mg daily, titrate to 25 mg 1, 5
• Hydrochlorothiazide: Start 25 mg daily, titrate to 50 mg (if chlorthalidone unavailable) 1
• Amlodipine: Start 5 mg daily, titrate to 10 mg 1

Titrate to maximum tolerated dose before adding a second agent to avoid underdosing, which is a common pitfall 2

Blood Pressure Targets

• Adults <65 years: <130/80 mm Hg 2
• Adults ≥65 years: Systolic <130 mm Hg if tolerated 2
• Home blood pressure monitoring target: <135/85 mm Hg 2

Monitoring Schedule

• Follow-up monthly after initiation or medication changes until blood pressure target achieved 2
• Check potassium and creatinine within 7-14 days when starting or changing dose of ACE inhibitor or ARB 2
• Reassess every 2-4 weeks during titration phase 1

Critical Pitfalls to Avoid

1. Using hydrochlorothiazide 12.5 mg as monotherapy: This dose provides inadequate 24-hour blood pressure control and may create masked hypertension 7
2. Underdosing medications: Titrate to maximum tolerated dose before adding additional agents 2
3. Using beta-blockers as first-line without specific cardiac indication (prior MI, angina, heart failure), as they are less effective for stroke prevention 1, 2
4. Failing to monitor electrolytes: Check potassium within 7-14 days when using ACE inhibitors, ARBs, or diuretics 2
5. Not addressing medication adherence barriers: Cost and side effects are common reasons for treatment failure in resistant hypertension 1