What treatment options are available for a patient with hypertension?

Treatment Options for Hypertension

Start with combination therapy using a thiazide-like diuretic (chlorthalidone or indapamide) plus either an ACE inhibitor/ARB or a calcium channel blocker, targeting blood pressure <130/80 mmHg for most adults under 65 years. 1, 2

Initial Pharmacologic Approach

First-Line Combination Therapy

• Begin with dual therapy immediately rather than monotherapy, combining a thiazide-like diuretic with either a renin-angiotensin system (RAS) blocker (ACE inhibitor like lisinopril or ARB like losartan) or a dihydropyridine calcium channel blocker (CCB) like amlodipine 1, 2, 3
• Prefer chlorthalidone 12.5-25 mg or indapamide 1.5 mg over hydrochlorothiazide, as thiazide-like diuretics provide superior blood pressure control 4
• Use once-daily dosing and single-pill combinations to maximize adherence 2

Target Blood Pressure Goals

• For adults <65 years: aim for <130/80 mmHg 1, 2
• For adults ≥65 years: aim for systolic <130 mmHg 1
• For elderly patients with frailty or multiple comorbidities, a less aggressive target of <140/90 mmHg is acceptable 2
• Home blood pressure monitoring target should be <135/85 mmHg 2

Medication Titration Algorithm

Step 1: Optimize Initial Dual Therapy

• Start with low doses and titrate to maximum tolerated doses over 4-12 weeks 2
• Check blood pressure within 4 weeks of any medication adjustment 2
• Achieve target blood pressure within 3 months 2

Step 2: Add Third Agent if Uncontrolled

• If using ACE inhibitor/ARB + CCB, add a thiazide-like diuretic 1, 2
• If using ACE inhibitor/ARB + thiazide-like diuretic, add a CCB 1, 2
• Ensure all three medications are at optimal doses before proceeding 4

Step 3: Resistant Hypertension Management

If blood pressure remains uncontrolled on three optimized medications:

• First, verify true treatment resistance by confirming medication adherence (pill counts, pharmacy refills), proper blood pressure measurement technique with validated device and appropriate cuff size, and obtain out-of-office monitoring to exclude white coat hypertension 4
• Intensify lifestyle modifications: sodium restriction to <2 g/day, weight loss of 5-10% if overweight, regular aerobic exercise, and limit alcohol 1, 4
• Add spironolactone 25 mg once daily as the fourth agent, provided serum potassium is <4.6 mmol/L 1, 4
• Monitor serum potassium, sodium, and creatinine within 1 month of starting spironolactone 4

Alternative Fourth-Line Agents

If spironolactone is not tolerated or contraindicated:

• Eplerenone (alternative mineralocorticoid receptor antagonist) 1
• Amiloride (potassium-sparing diuretic) 1, 4
• Bisoprolol (beta-blocker) 1
• Doxazosin (alpha-blocker) 1, 4
• Higher-dose thiazide-like diuretic or loop diuretic 1

Lifestyle Modifications (Essential for All Patients)

• Dietary sodium restriction: reduce intake to <2 g/day 1, 4, 3
• Weight loss: even 5-10% reduction in body weight significantly lowers blood pressure 4, 3
• DASH dietary pattern: emphasize fruits, vegetables, whole grains, low-fat dairy, and limit saturated fats 3
• Potassium supplementation: increase dietary potassium intake 3
• Regular physical activity: aerobic exercise most days of the week 4, 3, 5
• Alcohol moderation or elimination: limit or cease alcohol consumption 1, 3

Special Populations and Considerations

Race-Based Considerations

• For Black patients: combination therapy with a CCB plus either a thiazide-like diuretic or RAS blocker is particularly effective 1
• ACE inhibitors and ARBs have smaller blood pressure effects as monotherapy in Black patients, making combination therapy especially important 6, 3

Patients with Comorbidities

• Heart failure: ACE inhibitors (lisinopril) or ARBs are indicated to reduce signs, symptoms, and mortality 6
• Post-myocardial infarction: ACE inhibitors reduce mortality when started within 24 hours in hemodynamically stable patients 6
• Chronic kidney disease: RAS blockers are preferred 2
• Diabetes: target <130/80 mmHg with RAS blocker-based therapy 2

Monitoring Strategy

• Initial phase: check blood pressure within 4 weeks of starting or adjusting medications 2
• Maintenance phase: monitor every 3-6 months once at goal 2
• Use validated automated upper arm cuff devices with appropriate cuff size 2, 4
• Implement home blood pressure monitoring to guide therapy and detect white coat hypertension 2, 4
• For patients on spironolactone: monitor electrolytes and renal function within 1 month and periodically thereafter 4

Critical Pitfalls to Avoid

• Never use monotherapy in high-risk patients with established cardiovascular disease, diabetes, or chronic kidney disease 2
• Do not use immediate-release nifedipine for hypertensive crises due to unpredictable blood pressure drops 7, 8
• Avoid sodium nitroprusside when possible due to significant toxicity 7, 8
• Do not use hydralazine as first-line for acute severe hypertension 1, 7, 8
• Replace hydrochlorothiazide with chlorthalidone or indapamide for superior efficacy 4

When to Refer to Specialist

Refer to a hypertension specialist if:

• Blood pressure remains uncontrolled despite adherence to four-drug regimen at optimal doses 4
• Suspected secondary hypertension requiring further evaluation 5
• Consideration for renal denervation in resistant hypertension at medium-to-high volume centers 1