What is the initial treatment approach for hypertension?

Initial Treatment Approach for Hypertension

For most patients with confirmed hypertension (BP ≥140/90 mmHg), initiate combination therapy with two antihypertensive medications from different classes—specifically an ACE inhibitor or ARB plus either a dihydropyridine calcium channel blocker or thiazide-like diuretic—alongside lifestyle modifications. 1, 2

Confirming the Diagnosis

Before initiating treatment, confirm hypertension using proper measurement technique:

• Use a validated automated upper arm cuff device with appropriate cuff size 3, 1
• Measure BP in both arms at first visit and use the arm with higher readings 3, 1
• Confirm office BP ≥140/90 mmHg with either home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) 3, 1

Lifestyle Modifications (Start Immediately for All Patients)

Implement the following evidence-based lifestyle interventions concurrently with pharmacological therapy:

• Dietary pattern: Follow DASH or Mediterranean diet with reduced sodium intake (<2g/day sodium), increased potassium intake, and consumption of low-fat dairy products 3, 2, 4
• Physical activity: At least 150 minutes of moderate-intensity aerobic exercise per week plus resistance training 2-3 times weekly 2
• Weight management: Target BMI 20-25 kg/m² if overweight or obese 3, 2, 4
• Alcohol moderation: Limit to <100g/week of pure alcohol, or preferably complete avoidance 2
• Smoking cessation: Complete cessation with appropriate supportive care 2

These lifestyle modifications can reduce BP by approximately 5-10 mmHg and enhance the efficacy of pharmacological therapy. 5, 4

Pharmacological Therapy Algorithm

Initial Drug Selection Based on BP Level and Risk

For BP ≥160/100 mmHg or BP ≥140/90 mmHg with high cardiovascular risk (established CVD, CKD, diabetes, target organ damage, or age 50-80 years):

• Start two-drug combination therapy immediately alongside lifestyle modifications 3, 2
• Preferably use single-pill combinations to improve medication adherence 3

For BP 140-159/90-99 mmHg in low-moderate risk patients:

• May start with single-drug therapy, though two-drug combination is increasingly preferred 3
• If starting with monotherapy, escalate to combination therapy if target not achieved within 3 months 3, 2

Specific Drug Combinations by Patient Population

For non-Black patients without specific comorbidities:

1. First-line: ACE inhibitor or ARB + dihydropyridine calcium channel blocker OR ACE inhibitor or ARB + thiazide-like diuretic 3, 1, 2
2. If inadequate response: Increase to full doses 3
3. If still inadequate: Add third agent (thiazide-like diuretic if not already included) to create triple therapy 3, 2

For Black patients:

1. First-line: ARB + dihydropyridine calcium channel blocker OR dihydropyridine calcium channel blocker + thiazide-like diuretic 3, 2
   • Note: ACE inhibitors and ARBs are less effective as monotherapy in Black patients, but combination therapy overcomes this limitation 3

For patients with diabetes:

• First-line: ACE inhibitor or ARB (at maximum tolerated dose) as part of initial combination therapy 3
• Add dihydropyridine calcium channel blocker or thiazide-like diuretic as second agent 3
• For those with albuminuria (UACR ≥30 mg/g), ACE inhibitor or ARB is mandatory to reduce progressive kidney disease 3

For patients with established coronary artery disease:

• First-line: ACE inhibitor or ARB as part of combination therapy 3

For patients with chronic kidney disease:

• First-line: ACE inhibitor or ARB as part of initial therapy 1, 2

Specific Drug Classes and Dosing

The four first-line antihypertensive classes demonstrated to reduce cardiovascular events are:

• ACE inhibitors (e.g., lisinopril 10-40 mg daily, enalapril 5-40 mg daily) 3, 6, 7, 4
• ARBs (angiotensin receptor blockers) 3, 4
• Thiazide-like diuretics (e.g., chlorthalidone preferred over hydrochlorothiazide) 3, 4
• Dihydropyridine calcium channel blockers (e.g., amlodipine) 3, 4

Critical caveat: Never combine ACE inhibitors with ARBs, or combine either with direct renin inhibitors—these combinations increase harm without additional benefit. 3, 2

Special Considerations for Monotherapy

Consider starting with single-drug therapy only in:

• Low-risk patients with grade 1 hypertension (140-159/90-99 mmHg) 3, 2
• Patients >80 years of age 3, 2
• Frail patients 3, 2

For these patients, start with low-dose ACE inhibitor or ARB and titrate as needed. 3

Blood Pressure Targets

• Adults <65 years: Target BP <130/80 mmHg 1, 2
• Adults 65-85 years: Target systolic BP 120-129 mmHg if well tolerated 1, 2
• Adults >85 years: Target systolic BP 130-139 mmHg if well tolerated, individualized based on frailty 2
• Patients with diabetes: Target BP <130/80 mmHg 3
• Patients with CKD (eGFR >30 mL/min/1.73m²): Target systolic BP 120-129 mmHg 1

Monitoring and Titration

• Achieve target BP within 3 months of initiating therapy 3, 1, 2
• Schedule monthly visits until BP target is achieved 2
• Check serum creatinine and potassium 7-14 days after initiating or changing doses of ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1, 2
• Monitor at least annually thereafter for patients on these agents 3
• Consider home BP monitoring to guide medication adjustments 2

Resistant Hypertension (If BP Not Controlled on Three Drugs)

If BP remains ≥140/90 mmHg despite appropriate lifestyle management plus three antihypertensive drugs (including a diuretic) at adequate doses:

1. Exclude: Medication non-adherence, white coat hypertension, secondary hypertension 3
2. Add: Mineralocorticoid receptor antagonist (spironolactone) as fourth-line agent 3
3. Alternatives if spironolactone not tolerated: Amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 3

Common Pitfalls to Avoid

• Do not use beta-blockers as first-line therapy unless patient has prior MI, active angina, or heart failure with reduced ejection fraction—they have not been shown to reduce mortality as BP-lowering agents alone 3
• Do not preferentially dose antihypertensives at bedtime—this practice is not supported by recent evidence 3
• Do not delay treatment in high-risk patients waiting for lifestyle modifications alone to work—start pharmacotherapy immediately 3, 2
• Do not undertitrate medications—use adequate doses and combinations to achieve target BP within 3 months 3, 2