What is the recommended treatment approach for a patient with essential hypertension?

Essential Hypertension: Treatment Approach

Initial Pharmacological Therapy

For most adults with confirmed essential hypertension, initiate treatment with combination therapy using two first-line agents from different classes: a thiazide/thiazide-like diuretic, ACE inhibitor or ARB, or long-acting dihydropyridine calcium channel blocker, preferably as a single-pill combination to improve adherence. 1

First-Line Drug Classes (Strong Evidence)

The WHO and recent guidelines identify four equally effective first-line medication classes 1:

• Thiazide or thiazide-like diuretics (chlorthalidone 12.5-25mg daily preferred over hydrochlorothiazide 25-50mg due to longer duration of action) 1, 2
• ACE inhibitors (e.g., lisinopril 10-40mg daily, enalapril) 1, 3
• Angiotensin receptor blockers (ARBs) (e.g., losartan 50-100mg daily, candesartan, valsartan) 1, 3
• Long-acting dihydropyridine calcium channel blockers (e.g., amlodipine 5-10mg daily) 1, 3

Preferred Initial Combinations

Start with a two-drug combination rather than monotherapy for most patients, as combination therapy achieves target blood pressure faster and more effectively 1, 4:

• RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker 1, 4
• RAS blocker + thiazide/thiazide-like diuretic 1, 4
• Calcium channel blocker + thiazide diuretic (particularly effective in Black patients) 2, 4

Blood Pressure Targets

General Population

Target blood pressure <140/90 mmHg for all hypertensive patients without comorbidities (minimum acceptable target) 1:

• For patients <65 years: aim for <130/80 mmHg 1, 3
• For patients ≥65 years: aim for systolic <130 mmHg 1, 3
• Optimal target if well-tolerated: 120-129/70-79 mmHg 4

High-Risk Patients

For patients with known cardiovascular disease, target systolic blood pressure <130 mmHg (strong recommendation) 1:

• Patients with diabetes mellitus: <130/80 mmHg 1, 5
• Patients with chronic kidney disease: <130/80 mmHg 1, 5
• Patients with high cardiovascular risk (≥10% 10-year ASCVD risk): <130/80 mmHg 1

Critical Caveat on Diastolic Pressure

Avoid lowering diastolic blood pressure below 60 mmHg, particularly in patients >60 years with diabetes or coronary artery disease, as this increases cardiovascular risk 1:

• Optimal diastolic target: 70-80 mmHg in high-risk patients 1

Treatment Initiation Strategy by Blood Pressure Stage

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

For patients with stage 1 hypertension and 10-year ASCVD risk <10%, initiate lifestyle modifications alone and reassess in 3-6 months 1:

• For patients with stage 1 hypertension and 10-year ASCVD risk ≥10%, existing CVD, diabetes, or chronic kidney disease: initiate both lifestyle modifications AND pharmacological therapy immediately 1

Stage 2 Hypertension (≥140/90 mmHg)

For all patients with stage 2 hypertension, initiate combination pharmacological therapy with two agents from different classes immediately, along with lifestyle modifications 1:

• For blood pressure ≥160/100 mmHg: start two-drug combination therapy, monitor closely, and uptitrate rapidly to achieve control 1

Race-Specific Considerations

Black Patients

For Black patients, initial therapy should prioritize a dihydropyridine calcium channel blocker or thiazide diuretic, either alone or in combination 2, 4:

• The combination of calcium channel blocker + thiazide diuretic is more effective than calcium channel blocker + ACE inhibitor/ARB in Black patients 2, 4
• ACE inhibitors and ARBs are less effective as monotherapy in Black patients 6, 7

Non-Black Patients

For non-Black patients, any first-line agent or combination is appropriate, with ACE inhibitors or ARBs preferred when diabetes or chronic kidney disease is present 1, 4, 7

Escalation to Triple Therapy

If blood pressure remains uncontrolled on two-drug therapy at optimal doses, add a third agent to create the guideline-recommended triple therapy: RAS blocker + calcium channel blocker + thiazide diuretic 1, 2, 4:

• This combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 2
• Reassess blood pressure within 2-4 weeks after adding the third agent 1, 4

Resistant Hypertension (Fourth-Line Therapy)

For patients with blood pressure remaining ≥140/90 mmHg despite adherence to optimal doses of three-drug therapy (including a diuretic), add spironolactone 25-50mg daily as the preferred fourth-line agent 2, 4:

• Before adding a fourth agent, confirm medication adherence (most common cause of apparent resistance) and rule out secondary hypertension 2, 4
• Monitor serum potassium and creatinine 1-2 weeks after initiating spironolactone, especially when combined with ACE inhibitors or ARBs 2, 5, 4
• Alternative fourth-line agents if spironolactone contraindicated: eplerenone, amiloride, doxazosin, or beta-blocker 2, 4

Lifestyle Modifications (Essential for All Patients)

Implement the following lifestyle interventions, which provide additive blood pressure reductions of 5-20 mmHg and enhance medication efficacy 1, 4, 3:

• Dietary sodium restriction to <2.3g (100 mmol) daily 4, 3, 7
• DASH diet: emphasize fruits, vegetables, whole grains, low-fat dairy, reduced saturated fat 4, 3
• Weight loss if overweight: target BMI 18.5-24.9 kg/m² and waist circumference <102cm (men) or <88cm (women) 4, 6, 7
• Aerobic exercise 150 minutes/week moderate-intensity or 75 minutes/week vigorous-intensity, plus resistance training 2-3 times/week 4, 3
• Alcohol limitation: <14 units/week (men) or <8 units/week (women), preferably none 4, 6, 7
• Smoking cessation 4

Monitoring Schedule

Follow-up monthly after initiating or changing antihypertensive medications until target blood pressure is achieved 1:

• Once blood pressure is controlled, reassess every 3-5 months 1
• Check electrolytes and renal function 2-4 weeks after initiating or uptitrating ACE inhibitors, ARBs, or diuretics 1, 2
• Encourage home blood pressure monitoring with target <135/85 mmHg 4

Medications to Avoid

Do not use the following agents or combinations 1:

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure with reduced ejection fraction 1
• Alpha-blockers (doxazosin) as first-line therapy due to increased heart failure risk 1
• Combination of ACE inhibitor + ARB (increases adverse events without benefit) 1, 5
• Beta-blockers as first-line therapy in uncomplicated hypertension (less effective than other first-line agents, particularly in patients ≥60 years) 4, 7

Special Populations

Heart Failure with Reduced Ejection Fraction

For patients with hypertension and heart failure, use evidence-based heart failure medications that also lower blood pressure: ACE inhibitors or ARBs, beta-blockers (carvedilol, metoprolol succinate, bisoprolol), aldosterone antagonists, and diuretics 1:

• Target blood pressure <130/80 mmHg, consider <120/80 mmHg if tolerated 1
• Avoid non-dihydropyridine calcium channel blockers and alpha-blockers 1

Diabetes Mellitus

For patients with diabetes and hypertension, initiate ACE inhibitor or ARB as first-line therapy, targeting blood pressure <130/80 mmHg 1, 5, 7:

• If albuminuria absent, thiazide diuretics or dihydropyridine calcium channel blockers are also appropriate first-line options 7

Chronic Kidney Disease

For patients with chronic kidney disease (with or without proteinuria), use ACE inhibitor or ARB as part of the treatment regimen, targeting blood pressure <130/80 mmHg 1, 4, 7

Critical Pitfalls to Avoid

• Do not delay treatment intensification in stage 2 hypertension or when blood pressure remains >20/10 mmHg above target—this increases cardiovascular risk 2, 4
• Do not uptitrate a single agent to maximum dose before adding a second drug class—combination therapy is more effective than monotherapy dose escalation 2, 4
• Do not assume treatment failure without confirming adherence (use pill counts, pharmacy refill data, or consider directly observed therapy) 2, 4
• Do not ignore white coat hypertension—confirm diagnosis with home blood pressure monitoring or 24-hour ambulatory monitoring before intensifying therapy 1, 2
• Do not overlook secondary causes of hypertension in young patients (<30 years), those with resistant hypertension, or those with sudden onset/worsening hypertension 1, 4