What are the initial treatment recommendations for patients with hypertension?

Initial Treatment Recommendations for Hypertension

For most patients with hypertension, initiate treatment with a thiazide-type diuretic (preferably chlorthalidone 12.5-25 mg daily), an ACE inhibitor/ARB, or a long-acting dihydropyridine calcium channel blocker, with combination therapy recommended for those with BP ≥150/90 mmHg or stage 2 hypertension. 1, 2

Blood Pressure Thresholds for Initiating Pharmacotherapy

• Start pharmacological treatment immediately for patients with confirmed BP ≥140/90 mmHg 1
• Start treatment at BP 130-139/80-89 mmHg in high-risk patients with existing cardiovascular disease, diabetes, chronic kidney disease, or target organ damage 1, 2
• Combine with lifestyle modifications in all patients regardless of BP level 2, 3

First-Line Medication Classes

The following four drug classes have proven efficacy in reducing cardiovascular morbidity and mortality 1:

• Thiazide/thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide) 1, 4
• ACE inhibitors or ARBs (not both simultaneously) 1
• Long-acting dihydropyridine calcium channel blockers 1
• Beta-blockers are no longer first-line except for specific cardiac indications, as they are less effective for stroke prevention 1

Why Chlorthalidone Over Hydrochlorothiazide

Chlorthalidone is superior to hydrochlorothiazide for BP reduction, particularly for 24-hour ambulatory BP control. 4 At recommended doses, chlorthalidone 25 mg reduces systolic BP by approximately 5 mm Hg more than hydrochlorothiazide 50 mg, especially during nighttime hours. 4 Chlorthalidone was the diuretic used in landmark trials (ALLHAT, SHEP) that demonstrated cardiovascular event reduction. 1, 5

Monotherapy vs. Combination Therapy Algorithm

Start with Combination Therapy if:

• BP ≥150/90 mmHg (≥20/10 mm Hg above target) 1, 2
• Stage 2 hypertension 1, 2
• Use two first-line agents from different classes, preferably as single-pill combination 1, 6

Start with Monotherapy if:

• Stage 1 hypertension (BP 130-149/80-89 mmHg) with BP goal <130/80 mmHg 1, 2
• Begin with lower doses and titrate up before adding second agent 2

Preferred Combination Strategies

The most effective two-drug combinations include 1, 6:

• ACE inhibitor or ARB + dihydropyridine calcium channel blocker
• ACE inhibitor or ARB + thiazide/thiazide-like diuretic
• Calcium channel blocker + thiazide/thiazide-like diuretic

Never combine ACE inhibitor with ARB due to increased adverse effects without additional benefit 1

Population-Specific Recommendations

Black Patients

• Initial therapy should include thiazide-type diuretic or calcium channel blocker, either alone or combined with each other 1, 2
• ACE inhibitors/ARBs are less effective as monotherapy in Black patients but can be added as second agents 1

Patients with Chronic Kidney Disease or Albuminuria

• Use ACE inhibitor or ARB as first-line therapy, particularly with UACR ≥30 mg/g 2
• These agents provide renal protection beyond BP lowering 2

Patients with Coronary Artery Disease

• ACE inhibitor or ARB recommended as first-line therapy 2
• Thiazide diuretics remain appropriate and effective in this population 5

Elderly Patients (>80 years) or Frail Patients

• Consider starting with monotherapy at lower doses 2
• Target systolic BP 130-139 mmHg rather than <130 mmHg 1, 6

Specific Dosing Recommendations

Thiazide Diuretics

• Chlorthalidone: Start 12.5-25 mg once daily, maximum 50 mg daily 7, 4
• Hydrochlorothiazide: 12.5-25 mg once daily if chlorthalidone unavailable 1, 8

ACE Inhibitors

• Lisinopril: Start 10 mg once daily, usual range 20-40 mg daily 9
• Reduce to 5 mg once daily if starting with concurrent diuretic 9

Spironolactone (for Resistant Hypertension)

• Start 25 mg once daily as fourth-line agent 10, 6
• Monitor potassium and renal function within 1-2 weeks 6, 10

Blood Pressure Targets

• General target: <130/80 mmHg for most adults <65 years 1, 2
• For adults ≥65 years: Systolic <130 mmHg if tolerated 1, 3
• Achieve target within 3 months of treatment initiation 2

Critical Pitfalls to Avoid

• Underdosing medications before adding additional agents - titrate to maximum tolerated dose first 2, 11
• Using hydrochlorothiazide instead of chlorthalidone when diuretic is indicated - chlorthalidone provides superior 24-hour BP control 4
• Starting monotherapy in patients with BP >20/10 mm Hg above target - these patients require combination therapy from the start 1, 2
• Not monitoring potassium when using ACE inhibitors/ARBs - check within 7-14 days of initiation or dose change 2
• Failing to assess medication adherence before escalating therapy - nonadherence affects 10-80% of patients 6
• Allowing diastolic BP to drop below 60 mm Hg in high-risk patients with treated systolic BP <130 mm Hg, as this may increase cardiovascular events 1

Monitoring Schedule

• Monthly follow-up after initiation or medication changes until BP target achieved 1, 2
• Every 3-5 months once BP is controlled 1
• Home BP monitoring recommended with target <135/85 mmHg 2, 6