What is the recommended treatment approach for hypertension?

Hypertension Treatment

For most adults with confirmed hypertension, initiate treatment with combination therapy using two first-line agents—preferably a renin-angiotensin system (RAS) blocker (ACE inhibitor or ARB) combined with either a calcium channel blocker (CCB) or a thiazide/thiazide-like diuretic—as a single-pill combination to maximize adherence and achieve blood pressure targets of <130/80 mmHg for adults under 65 years. 1, 2

Initial Treatment Strategy

First-Line Drug Classes

The four major drug classes proven to reduce cardiovascular morbidity and mortality are: 1, 3

• ACE inhibitors (e.g., lisinopril, enalapril)
• Angiotensin receptor blockers (ARBs) (e.g., candesartan)
• Dihydropyridine calcium channel blockers (e.g., amlodipine)
• Thiazide or thiazide-like diuretics (e.g., hydrochlorothiazide, chlorthalidone)

Combination Therapy Approach

Start with two-drug combination therapy for most patients rather than monotherapy, as most hypertensive patients require multiple agents for adequate control. 2, 1 The preferred initial combinations are: 1

• RAS blocker + dihydropyridine CCB, OR
• RAS blocker + thiazide/thiazide-like diuretic

Use single-pill combinations whenever possible to improve adherence and allow once-daily dosing. 2, 1

When to Start with Monotherapy

The traditional stepped-care approach (single agent followed by sequential titration) is reasonable for: 2

• Older adults at risk for hypotension
• Patients with history of orthostatic hypotension
• Those with previous drug-associated side effects
• Patients requiring careful BP monitoring

When to Start with Two Agents

Initiate therapy with two agents immediately when BP is >20/10 mmHg above target, as these patients are at greater cardiovascular risk and require more rapid titration. 2

Blood Pressure Targets

• Adults <65 years: <130/80 mmHg 1
• Adults ≥65 years: Systolic 120-130 mmHg if tolerated 1
• Patients with diabetes or CKD: <130/80 mmHg 2, 1
• Minimal audit standard for all patients: <150/90 mmHg 2

Special Population Considerations

Black Patients

Initial treatment should include a diuretic or CCB, either alone or in combination with a RAS blocker. 1

Patients with Diabetes or CKD with Proteinuria

A RAS blocker must be included in the regimen. 1

Elderly Patients

Treatment may need more gradual initiation with consideration of frailty and comorbidities; monitor carefully for hypotension and orthostatic symptoms. 2, 1

Treatment Escalation Algorithm

Step 1: Start with two-drug combination (RAS blocker + CCB or diuretic) at low doses 1

Step 2: If BP remains uncontrolled after 2-4 weeks, uptitrate doses of the initial two agents 2

Step 3: If BP still uncontrolled, advance to triple therapy with RAS blocker + CCB + thiazide/thiazide-like diuretic, preferably as a single-pill combination 1

Step 4: For resistant hypertension (uncontrolled on three drugs including a diuretic), add low-dose spironolactone and consider specialist referral 2, 1

Specific Dosing Example (Lisinopril)

For hypertension in adults: 4

• Initial dose: 10 mg once daily
• Usual range: 20-40 mg once daily
• Maximum: 80 mg once daily (though doses above 40 mg show minimal additional benefit)
• If on diuretic: Start with 5 mg once daily

Essential Lifestyle Modifications

All patients should receive counseling on: 2, 1, 3

• Weight loss: 10 kg reduction yields approximately 6/4.6 mmHg BP reduction 2
• Dietary sodium restriction: <100 mEq/24 hours (ideally <2.3 g/day), which can lower BP by 5-10/2-6 mmHg 2
• DASH dietary pattern: High in fruits, vegetables, low-fat dairy, and potassium 3
• Physical activity: Regular aerobic exercise
• Alcohol moderation: ≤2 drinks per day for men, ≤1 for women 2
• Smoking cessation 1

Management of Resistant Hypertension

Resistant hypertension is defined as BP uncontrolled despite three or more drugs including a diuretic. 2, 1 Key steps include:

1. Verify true resistance: Rule out white coat hypertension with ambulatory or home BP monitoring 2
2. Assess adherence: Simplified regimens and home BP monitoring improve compliance 2, 1
3. Identify interfering substances: NSAIDs, decongestants, excessive alcohol, illicit drugs 2
4. Screen for secondary causes: Particularly in young patients, sudden onset/worsening, or those with hypokalemia 2
5. Evaluate for sleep apnea: Treat if present 2
6. Add spironolactone: Low-dose aldosterone antagonist is highly effective 1
7. Consider specialist referral for refractory cases 1

Critical Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB)—this increases adverse effects without additional benefit 1
• Avoid delayed intensification when BP remains uncontrolled; reassess and adjust therapy within 2-4 weeks 2, 1
• Do not overlook medication adherence before adding new agents—use pill counts, pharmacy refill data, or directly observed therapy if needed 2
• Monitor for orthostatic hypotension when initiating two-drug therapy in elderly patients 2
• Ensure adequate diuretic dosing in resistant hypertension—many patients are undertreated with suboptimal diuretic doses 2

Monitoring and Follow-Up

• Initial follow-up: 2-4 weeks after starting or adjusting therapy 2
• Once controlled: Monitor every 3-6 months 2
• Home BP monitoring: Improves adherence and provides more accurate assessment than office readings alone 2, 1
• Team-based care: Involving nurse case managers, pharmacists, and nutritionists improves outcomes in difficult-to-control patients 2

Expected Treatment Response

• 25-50% of patients will achieve target BP with initial two-drug therapy 2
• Approximately 25% will require additional treatment adjustments 2
• A 10 mmHg systolic BP reduction decreases cardiovascular events by 20-30% 3
• Currently, only 44% of US adults with hypertension achieve control to <140/90 mmHg, highlighting the need for aggressive treatment strategies 3