What is the recommended treatment plan for an otherwise healthy adult with hypertension (blood pressure ≥130/80 mm Hg)?

Treatment of High Blood Pressure in Otherwise Healthy Adults

For an otherwise healthy adult with hypertension (BP ≥130/80 mmHg), begin with intensive lifestyle modification for up to 3 months if BP is 130-139/80-89 mmHg and 10-year ASCVD risk is <10%; if BP remains elevated or if BP is ≥140/90 mmHg at diagnosis, initiate pharmacologic therapy with a thiazide or thiazide-like diuretic, ACE inhibitor/ARB, or calcium channel blocker, targeting <130/80 mmHg. 1, 2

Blood Pressure Classification and Treatment Thresholds

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

• Initiate lifestyle modifications immediately for all patients with BP ≥130/80 mmHg 1
• Start pharmacologic therapy at BP ≥130/80 mmHg if 10-year ASCVD risk is ≥10% 1
• Start pharmacologic therapy at BP ≥140/90 mmHg regardless of ASCVD risk after maximum 3 months of lifestyle intervention 1, 3

Stage 2 Hypertension (≥160/100 mmHg)

• Initiate two antihypertensive agents immediately (or a single-pill combination) when BP is ≥160/100 mmHg or >20/10 mmHg above target 1, 4
• Treat promptly with careful monitoring and adjust regimen monthly until control is achieved 1

First-Line Pharmacologic Therapy

Preferred Initial Agents (Choose One)

The three first-line drug classes have equivalent efficacy for reducing cardiovascular events and mortality: 2, 3

1. Thiazide or thiazide-like diuretics 2, 3

   • Chlorthalidone 12.5-25 mg once daily (preferred due to longer half-life and superior cardiovascular outcomes) 4, 5, 6
   • Hydrochlorothiazide 25 mg once daily (acceptable alternative) 4, 7
   • Indapamide 1.25-2.5 mg once daily (acceptable thiazide-like alternative) 5

2. ACE inhibitors or ARBs 2, 3

   • Lisinopril 10 mg once daily (titrate to 20-40 mg) 7
   • Enalapril, ramipril, or other ACE inhibitors 2
   • Losartan, valsartan, candesartan, or other ARBs 2, 3

3. Calcium channel blockers 2, 3

   • Amlodipine 5-10 mg once daily 4, 2
   • Other long-acting dihydropyridines 8

Special Population Considerations

• For Black patients: Initiate with calcium channel blocker or thiazide diuretic rather than ACE inhibitor/ARB as monotherapy 4, 3
• Beta-blockers are NOT first-line unless compelling indications exist (heart failure, post-MI, angina, atrial fibrillation) 4, 5, 3

Combination Therapy Algorithm

When to Add a Second Agent

Add a second drug if BP remains ≥130/80 mmHg after 4 weeks of monotherapy at optimal dose (or immediately if stage 2 hypertension) 1, 4

Preferred Two-Drug Combinations

1. ACE inhibitor/ARB + calcium channel blocker 4, 2
2. ACE inhibitor/ARB + thiazide diuretic 4, 2
3. Calcium channel blocker + thiazide diuretic 4, 2

Single-pill combinations are strongly preferred to improve adherence 1, 4

Triple Therapy (Third Agent)

Add a third agent if BP remains ≥130/80 mmHg on two-drug therapy: 1, 4

• Standard triple therapy: ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic 1, 4
• This combination targets three complementary mechanisms: renin-angiotensin blockade, vasodilation, and volume reduction 4

Resistant Hypertension (Fourth Agent)

If BP remains ≥140/90 mmHg despite optimized triple therapy: 1, 4

• Add spironolactone 25-50 mg daily as the preferred fourth-line agent 1, 4
• Provides additional BP reduction of approximately 20-25/10-12 mmHg 4
• Monitor potassium and creatinine 2-4 weeks after initiation 4

Blood Pressure Targets

General Adult Population

• Primary target: <130/80 mmHg for most adults <65 years 1, 2
• Minimum acceptable: <140/90 mmHg 1, 8, 3

Older Adults (≥65 years)

• Target: <130 mmHg systolic if well tolerated 1
• For adults ≥80 years: Target systolic 130-139 mmHg, individualized based on frailty 1, 5
• Minimum acceptable: <150/90 mmHg for very elderly or frail 9, 3

Special Populations

• Diabetes mellitus: <130/80 mmHg 1
• Chronic kidney disease: 120-129 mmHg systolic if eGFR >30 mL/min/1.73m² 1
• Post-stroke/TIA: 120-129 mmHg systolic 1

Lifestyle Modifications (Essential for All Patients)

Comprehensive lifestyle changes can reduce BP by 10-20 mmHg and enhance medication efficacy: 1, 4, 2

• Sodium restriction to <2 g/day: Reduces systolic BP by 5-10 mmHg 1, 4, 2
• DASH dietary pattern: Reduces BP by 11.4/5.5 mmHg 4, 2
• Weight loss (if overweight): 10 kg loss reduces BP by approximately 6/4.6 mmHg 4, 2
• Regular aerobic exercise: ≥30 minutes most days reduces BP by 4/3 mmHg 4, 2
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 4, 2
• Smoking cessation 8

Monitoring and Follow-Up

Initial Monitoring

• Reassess BP 2-4 weeks after initiating or adjusting therapy 1, 4
• Monthly follow-up until BP is controlled 1
• Goal: Achieve target BP within 3 months of treatment initiation or modification 1, 4

Laboratory Monitoring

• Check serum potassium and creatinine 2-4 weeks after starting ACE inhibitor/ARB or diuretic 4
• Screen for orthostatic hypotension in older adults (measure BP after 1 and 3 minutes of standing) 1

Confirmation of Diagnosis

• Confirm elevated office readings with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) before initiating therapy 1, 4, 8

Critical Pitfalls to Avoid

• Never combine ACE inhibitor with ARB (dual RAS blockade increases hyperkalemia and acute kidney injury without cardiovascular benefit) 1, 4
• Do not use beta-blockers as first-line in uncomplicated hypertension (less effective for stroke prevention) 4, 5
• Do not delay treatment intensification in stage 2 hypertension (≥160/100 mmHg requires prompt action) 1, 4
• Always verify medication adherence before escalating therapy (non-adherence is the most common cause of apparent treatment resistance) 4
• Screen for secondary hypertension if BP remains severely elevated (≥180/110 mmHg) or resistant to triple therapy 4
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure 4

Evidence for Benefit

A 10 mmHg reduction in systolic BP decreases cardiovascular events by 20-30% and significantly reduces risk of stroke, myocardial infarction, heart failure, and death 2, 8