What is the recommended treatment for hypertension?

Hypertension Treatment

For most adults with confirmed hypertension, initiate combination therapy immediately with two first-line agents—specifically a RAS blocker (ACE inhibitor or ARB) combined with either a calcium channel blocker or thiazide/thiazide-like diuretic—preferably as a single-pill combination to improve adherence and achieve target blood pressure. 1, 2

Blood Pressure Targets

• Target systolic BP 120-129 mmHg and diastolic BP <80 mmHg for adults <65 years if well tolerated 1, 2
• Target systolic BP 130-139 mmHg for adults ≥65 years 1
• Target <130/80 mmHg for high-risk patients with diabetes, chronic kidney disease, or established cardiovascular disease 3, 1

The 2020 International Society of Hypertension guidelines specify BP should be lowered if ≥140/90 mmHg, with targets <130/80 mmHg (<140/80 in elderly patients) across most comorbid conditions. 3 However, the most recent 2025 guidelines from the European Society of Cardiology recommend more aggressive targets of 120-129 mmHg systolic for most adults if tolerated, representing an evolution toward tighter control based on cardiovascular outcome data. 1, 2

Pharmacological Treatment Algorithm

Step 1: Initial Dual Therapy

• Start with two-drug combination at low doses: RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker OR a thiazide/thiazide-like diuretic 1, 2
• Prescribe as a single-pill fixed-dose combination whenever possible to enhance adherence 1, 2
• For example, lisinopril 10 mg once daily can be initiated, with consideration for adding hydrochlorothiazide 12.5 mg if BP remains uncontrolled 4

Step 2: Triple Therapy Escalation

• If BP remains uncontrolled after 4 weeks, escalate to triple therapy: RAS blocker + calcium channel blocker + thiazide/thiazide-like diuretic, preferably as a single-pill combination 1, 2
• The usual dosage range for ACE inhibitors like lisinopril is 20-40 mg per day, with doses up to 80 mg studied but not providing greater effect 4

Step 3: Resistant Hypertension

• Add a mineralocorticoid receptor antagonist (spironolactone) as the fourth agent for resistant hypertension 3

Special Population Considerations

Black Patients

• Initial therapy should include a thiazide-like diuretic plus calcium channel blocker, or calcium channel blocker plus ARB 1, 2
• This recommendation differs from the general population due to evidence showing smaller BP effects with RAS blocker monotherapy in Black patients 5

Coronary Artery Disease

• Target BP <130/80 mmHg (<140/80 in elderly) 3
• Use RAS blockers and beta-blockers as first-line agents, with or without calcium channel blockers 3, 1
• Add lipid-lowering treatment targeting LDL-C <55 mg/dL (1.4 mmol/L) 3
• Antiplatelet therapy with aspirin is routinely recommended 3

Heart Failure

• For HFrEF: Use RAS blockers, beta-blockers, and mineralocorticoid receptor antagonists; consider ARNI (sacubitril-valsartan) as alternative to ACE inhibitor/ARB 3, 1
• For HFpEF: Consider SGLT2 inhibitors for symptomatic patients 2
• Target BP <130/80 mmHg but >120/70 mmHg 3
• Lisinopril starting dose is 5 mg once daily when used with diuretics and digitalis, with 2.5 mg for patients with hyponatremia (serum sodium <130 mEq/L) 4

Previous Stroke/TIA

• Target systolic BP 120-130 mmHg 1
• Use RAS blockers, calcium channel blockers, and diuretics as first-line agents 3, 1
• Add lipid-lowering treatment targeting LDL-C <70 mg/dL (1.8 mmol/L) for ischemic stroke 3
• Antiplatelet therapy is recommended for ischemic stroke but not hemorrhagic stroke 3

Chronic Kidney Disease

• Include RAS blocker when albuminuria/proteinuria is present due to superior albuminuria reduction 3, 1, 2
• Target systolic BP 120-129 mmHg for eGFR >30 mL/min/1.73m² 1
• Add calcium channel blockers and diuretics (loop diuretics if eGFR <30 mL/min/1.73m²) 3
• Monitor eGFR, microalbuminuria, and blood electrolytes at least annually 3, 2

Diabetes

• Initiate treatment at BP ≥140/90 mmHg and target <130/80 mmHg 3, 1, 2
• Use RAS inhibitor combined with calcium channel blocker and/or thiazide-like diuretic 3
• Add statin in primary prevention if LDL-C >70 mg/dL (1.8 mmol/L) with target organ damage or >100 mg/dL (2.6 mmol/L) for uncomplicated diabetes 3

Acute Myocardial Infarction

• In hemodynamically stable patients within 24 hours of symptom onset: Give lisinopril 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg once daily for at least 6 weeks 4
• Initiate with 2.5 mg in patients with low systolic BP (≤120 mmHg and >100 mmHg) during first 3 days 4
• If hypotension occurs (systolic BP ≤100 mmHg), maintain 5 mg daily with temporary reductions to 2.5 mg if needed 4

Pediatric Patients (≥6 years)

• Starting dose: 0.07 mg/kg once daily (up to 5 mg total) for glomerular filtration rate >30 mL/min/1.73m² 4
• Adjust according to BP response up to maximum 0.61 mg/kg (up to 40 mg) once daily 4
• Not recommended in children <6 years or with GFR <30 mL/min/1.73m² 4

Lifestyle Modifications

These interventions are foundational and should be implemented for all patients:

• Weight reduction: Target BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women) 1, 5
• Sodium restriction: <2,300 mg/day 2, 5
• Dietary pattern: 8-10 servings of fruits/vegetables daily and 2-3 servings of low-fat dairy products 2
• Physical activity: Minimum 150 minutes/week of moderate-intensity aerobic activity or 75 minutes/week of vigorous activity, plus resistance training 2-3 times weekly 1, 5
• Alcohol limitation: ≤2 drinks/day for men and ≤1 drink/day for women 2, 5
• Complete tobacco cessation with referral to smoking cessation programs 2
• Elimination of sugar-sweetened beverages and restriction of free sugar to maximum 10% of energy intake 2

The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. 5 An SBP reduction of 10 mmHg through any means decreases risk of cardiovascular events by approximately 20-30%. 5

Critical Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB) due to increased adverse effects without additional benefit 1
• Do not delay initiation of combination therapy in favor of monotherapy—this approach is outdated and delays BP control 1, 2
• Avoid prescribing multiple separate pills when single-pill combinations are available, as this significantly reduces adherence 1, 2
• Do not use beta-blockers as first-line therapy except in specific conditions (CAD, heart failure, post-MI) 3

Monitoring and Follow-Up

• Achieve target BP within 3 months of treatment initiation 2
• Use both office and home BP readings for regular monitoring 1
• Monitor renal function and potassium at least annually when using ACE inhibitor, ARB, or diuretic 2
• Continue lifelong BP-lowering treatment if well tolerated, even beyond age 85 1, 2
• Employ multidisciplinary team approaches involving pharmacists to enhance adherence 1