What's the best treatment for hypertension?

Hypertension Treatment

First-Line Pharmacological Therapy

For most adults with confirmed hypertension, initiate combination therapy with two drugs from the start: a RAS blocker (ACE inhibitor or ARB) combined with either a dihydropyridine calcium channel blocker or a thiazide/thiazide-like diuretic, preferably as a single-pill combination. 1, 2, 3

Preferred Initial Combinations:

• ACE inhibitor or ARB + calcium channel blocker (e.g., lisinopril + amlodipine) 1, 2
• ACE inhibitor or ARB + thiazide diuretic (e.g., losartan + hydrochlorothiazide) 1, 2
• Calcium channel blocker + thiazide diuretic (particularly for Black patients) 4, 2

The evidence strongly supports starting with dual therapy rather than monotherapy for confirmed hypertension (BP ≥140/90 mmHg), as this achieves target blood pressure faster and improves adherence when using fixed-dose combinations. 3, 5

Special Population Considerations:

• Black patients: Initiate with a dihydropyridine calcium channel blocker or thiazide diuretic, either alone or combined with a RAS blocker 4, 2
• Patients with diabetes or chronic kidney disease: Prioritize RAS blockers (ACE inhibitor or ARB) due to superior renal protection 1, 2
• Patients with heart failure: Add SGLT2 inhibitors for symptomatic HFpEF 2

Blood Pressure Targets

Target systolic BP of 120-129 mmHg for most adults if treatment is well tolerated, with a minimum acceptable target of <140/90 mmHg. 1, 2

• Diastolic target: <80 mmHg for all patients 1
• Older adults (≥65 years): Target systolic BP 130-139 mmHg 1
• Patients ≥85 years or with symptomatic orthostatic hypotension: Consider more lenient targets (e.g., <140 mmHg) 1
• High-risk patients (diabetes, CKD, established CVD): Target <130/80 mmHg 2, 5

Treatment Escalation Algorithm

If BP Uncontrolled on Two Drugs:

Add a third agent to create triple therapy: RAS blocker + calcium channel blocker + thiazide diuretic. 1, 4, 2

This combination targets three complementary mechanisms—renin-angiotensin system blockade, vasodilation, and volume reduction—and represents the guideline-recommended approach for uncontrolled hypertension. 1, 4

• Preferred thiazide-like diuretics: chlorthalidone 12.5-25mg daily (superior to hydrochlorothiazide due to longer half-life and better cardiovascular outcomes) or indapamide 1.25-2.5mg daily 1, 4
• Monitor serum potassium and creatinine 2-4 weeks after adding diuretic 4, 3

If BP Uncontrolled on Triple Therapy (Resistant Hypertension):

Add spironolactone 25-50mg daily as the preferred fourth-line agent. 1, 4

Before adding a fourth medication: 4

• Verify medication adherence (most common cause of apparent resistance)
• Rule out interfering substances: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, excessive alcohol (>2 drinks/day for men, >1 for women)
• Screen for secondary hypertension: primary aldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma
• Reinforce lifestyle modifications: sodium restriction to <2g/day, weight loss if BMI >25 kg/m²

Alternative fourth-line agents if spironolactone contraindicated: eplerenone, beta-blocker (if not already prescribed), centrally acting agent (clonidine), alpha-blocker (doxazosin), or hydralazine. 1

Lifestyle Modifications (Essential for All Patients)

These interventions provide additive BP reductions of 10-20 mmHg and should be implemented concurrently with pharmacological therapy: 1, 2, 5

• Weight reduction: Target BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) 1, 2
• Sodium restriction: <2g/day (approximately <5g salt/day) 1, 2, 3
• DASH diet: High consumption of vegetables, fruits, fish, nuts, unsaturated fatty acids; low consumption of red meat 1, 2
• Regular aerobic exercise: ≥150 minutes/week of moderate intensity or 75 minutes/week of vigorous intensity, plus resistance training 2-3 times/week 1, 2
• Alcohol limitation: <14 units/week for men, <8 units/week for women (preferably <100g/week of pure alcohol) 1, 2
• Tobacco cessation: Complete elimination with referral to cessation programs 2

Monitoring and Follow-Up

• Achieve target BP within 3 months of treatment initiation or modification 4, 2, 3
• Reassess BP within 2-4 weeks after any medication change 4, 3
• Monitor renal function and potassium at least annually when using ACE inhibitor, ARB, or diuretic 2
• Confirm diagnosis with out-of-office measurements: home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg 3

Critical Pitfalls to Avoid

• Never start with monotherapy for confirmed hypertension (BP ≥140/90 mmHg)—combination therapy is recommended from the outset 3
• Never combine two RAS blockers (ACE inhibitor + ARB)—this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1, 4
• Do not add beta-blockers as second or third agent unless compelling indications exist (angina, post-MI, heart failure with reduced ejection fraction, heart rate control needed) 1, 4
• Do not delay treatment intensification in patients with stage 2 hypertension (≥160/100 mmHg)—prompt action reduces cardiovascular risk 4
• Do not use non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with left ventricular dysfunction or heart failure 4