What are the treatment options for hypertension?

Hypertension Treatment Options

For most adults with confirmed hypertension, initiate combination therapy with two first-line agents—specifically a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic—preferably as a single-pill combination, targeting a blood pressure of <130/80 mmHg for adults under 65 years. 1, 2

Initial Assessment and Diagnosis

• Confirm hypertension diagnosis with office blood pressure measurements (average of 2-3 readings) and validate with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) 1
• Measure blood pressure in both arms simultaneously at the first visit; use the arm with consistently higher readings for subsequent measurements 1
• Check for orthostatic hypotension to assess for autonomic neuropathy, particularly in diabetic patients 1

Lifestyle Modifications (Foundation for All Patients)

All patients with hypertension or high-normal blood pressure should implement lifestyle changes regardless of whether pharmacotherapy is initiated. 1, 2, 3

• Weight reduction: Achieve body mass index of 18.5-24.9 kg/m² and waist circumference <102 cm in men, <88 cm in women 4, 5
• Sodium restriction: Limit intake to 65-100 mmol/day (<2,300 mg/day) 1, 4, 5
• DASH dietary pattern: Consume 8-10 servings of fruits/vegetables daily, 2-3 servings of low-fat dairy products, emphasize whole grains and plant-based protein 4, 6
• Physical activity: Perform 30-60 minutes of aerobic exercise 4-7 days per week 4, 5
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 4, 5
• Tobacco cessation: Complete elimination with referral to cessation programs 4
• Sugar restriction: Eliminate sugar-sweetened beverages and limit free sugar to maximum 10% of energy intake 4

The DASH diet combined with sodium restriction appears to be the most effective lifestyle intervention for blood pressure reduction. 3

Pharmacological Treatment Algorithm

Step 1: Initial Dual Therapy

For most non-Black patients:

• Start with low-dose ACE inhibitor or ARB plus either a dihydropyridine calcium channel blocker OR a thiazide/thiazide-like diuretic 1, 2, 6
• Use single-pill combinations whenever possible to improve adherence 2, 4
• Prescribe once-daily dosing regimens 1

For Black patients:

• Start with a diuretic or calcium channel blocker, either alone or in combination with a RAS blocker 1, 2
• For Black patients from Sub-Saharan Africa, use a calcium channel blocker combined with either a thiazide diuretic or RAS blocker 1

Exception—Monotherapy consideration:

• Low-risk grade 1 hypertension (140-159/90-99 mmHg without high-risk features) 1
• Patients aged >80 years or frail individuals 1

Step 2: Dose Optimization

• Increase to full doses of the initial two-drug combination before adding a third agent 1, 2
• Reassess blood pressure within 3 months to ensure target achievement 1, 4

Step 3: Triple Therapy

• Add the third drug class to create the core triple combination: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic 1, 2, 4
• Continue using single-pill combinations when available 2

Step 4: Resistant Hypertension Management

Resistant hypertension is defined as uncontrolled blood pressure despite three drugs including a diuretic. 1, 2

• First-line addition: Low-dose spironolactone (25-50 mg daily) 1, 2
• If spironolactone not tolerated or contraindicated: Consider eplerenone, amiloride, higher-dose thiazide/thiazide-like diuretic, or loop diuretic 1
• Additional options: Bisoprolol, doxazosin, clonidine, or hydralazine 1
• Reinforce lifestyle measures: Especially sodium restriction 1
• Consider referral: To hypertension specialist if blood pressure remains uncontrolled 1
• Catheter-based renal denervation: May be considered at medium-to-high volume centers after shared decision-making and multidisciplinary assessment 1

Blood Pressure Targets

• Adults <65 years: <130/80 mmHg 1, 2, 6
• Adults ≥65 years: Systolic 120-130 mmHg if tolerated 1, 2
• Patients with diabetes: <130/80 mmHg 1, 4
• Patients with chronic kidney disease (eGFR >30 mL/min/1.73 m²): Systolic 120-129 mmHg if tolerated 1, 4
• Patients with history of stroke or TIA: Systolic 120-130 mmHg 1

The 2024 ESC guidelines represent a shift toward more aggressive blood pressure targets (120-129 mmHg systolic) compared to older guidelines, reflecting recent trial evidence showing cardiovascular benefit with lower targets. 1

Special Population Considerations

Heart Failure

Heart failure with reduced ejection fraction (HFrEF):

• ACE inhibitor or ARB (or ARNI), beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor 1

Heart failure with preserved ejection fraction (HFpEF):

• SGLT2 inhibitors are recommended for symptomatic patients 1, 4
• ARBs and/or mineralocorticoid receptor antagonists may be considered to reduce heart failure hospitalizations 1

Chronic Kidney Disease

• RAS blockers (ACE inhibitors for type 1 and type 2 diabetes; ARBs for type 2 diabetes) are first-line therapy in the presence of microalbuminuria or proteinuria 1, 4
• RAS blockers are more effective than other antihypertensives at reducing albuminuria 1
• Monitor renal function and serum potassium at least annually 1, 4

Diabetes Mellitus

• ACE inhibitors or ARBs are preferred first-line agents 1
• If ACE inhibitors are not tolerated, ARBs should be used 1
• Beta-blockers and diuretics are also supported by evidence for cardiovascular event reduction 1
• Calcium channel blockers are appropriate additions but should not replace ACE inhibitors or beta-blockers as initial therapy 1

Elderly and Frail Patients

• Lower blood pressure gradually to avoid complications 1
• Consider frailty when setting targets; more conservative targets may be appropriate 1
• Maintain treatment lifelong, even beyond age 85, if well tolerated 4

Monitoring and Follow-Up

• Achieve target blood pressure within 3 months of treatment initiation 1, 4
• Home blood pressure monitoring: Provides feedback to patients and improves adherence 2
• Medication adherence assessment: Before adding new medications or increasing doses 2
• Renal function and electrolytes: Monitor at least annually when using ACE inhibitors, ARBs, or diuretics 4
• Blood pressure measurement: At every routine visit 1

Common Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB): This increases adverse effects without additional cardiovascular benefit 2
• Avoid delayed treatment intensification: If blood pressure remains uncontrolled after 3 months, escalate therapy promptly 2
• Do not use beta-blockers as first-line monotherapy in patients ≥60 years without compelling indications (e.g., heart failure, recent myocardial infarction, angina) 1, 5
• Assess adherence before assuming treatment failure: Poor adherence is a major cause of apparent resistant hypertension 2
• Do not neglect lifestyle modifications even when pharmacotherapy is required: Lifestyle changes enhance drug efficacy and may reduce medication requirements 3, 6

Drug Class-Specific Considerations

First-Line Agents

ACE Inhibitors (e.g., lisinopril, enalapril):

• Indicated for hypertension, heart failure, and post-myocardial infarction mortality reduction 7
• Monitor for cough (10-20% of patients), angioedema (rare but serious), hyperkalemia, and acute kidney injury 7

Thiazide/Thiazide-like Diuretics (e.g., chlorthalidone, hydrochlorothiazide):

• Chlorthalidone is preferred over hydrochlorothiazide due to longer duration of action and superior cardiovascular outcomes in trials 8, 6, 9
• Monitor for hypokalemia, hyponatremia, hyperuricemia, and hyperglycemia 8

Calcium Channel Blockers (dihydropyridines like amlodipine):

• Effective for isolated systolic hypertension 5
• Monitor for peripheral edema (common but benign) 6

Angiotensin Receptor Blockers (e.g., candesartan, losartan):

• Similar efficacy to ACE inhibitors with lower incidence of cough 6
• Use when ACE inhibitors are not tolerated 1, 4

The evidence strongly supports that achieving blood pressure control is more important than the specific drug sequence used, as long as first-line agents are employed. 1, 6 A 10 mmHg reduction in systolic blood pressure decreases cardiovascular events by approximately 20-30%. 6