What is the best initial treatment approach for a typical adult patient with hypertension?

Initial Treatment of Hypertension in Adults

For a typical adult with newly diagnosed hypertension, begin with upfront combination therapy using two medications—specifically an ACE inhibitor (or ARB) plus either a calcium channel blocker or thiazide-like diuretic—preferably as a single-pill combination, targeting a blood pressure goal of <130/80 mmHg. 1, 2

Confirming the Diagnosis

• Confirm hypertension using out-of-office measurements before initiating treatment: home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory BP monitoring (≥130/80 mmHg) 1, 2
• Measure blood pressure at every routine visit to establish the diagnosis 1

Initial Pharmacological Strategy

For Blood Pressure ≥140/90 mmHg (Stage 2 Hypertension)

Start with two-drug combination therapy immediately alongside lifestyle modifications 1, 2:

• Preferred combination: ACE inhibitor (lisinopril 10 mg daily) + thiazide-like diuretic (chlorthalidone 12.5-25 mg daily) 1, 2, 3
• Alternative combination: ACE inhibitor or ARB + dihydropyridine calcium channel blocker (amlodipine 5 mg daily) 1, 2
• Single-pill combinations are strongly preferred to improve adherence and achieve faster BP control 1

The 2024 ESC guidelines represent the most current evidence and explicitly recommend against delaying pharmacotherapy for lifestyle modification trials when BP is ≥140/90 mmHg 1, 2. This differs from older approaches that suggested waiting 3-6 months.

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

• Initiate both lifestyle modifications AND single-agent pharmacotherapy simultaneously 1, 2
• First-line agent: ACE inhibitor (lisinopril 10 mg daily) or ARB 2, 3
• Do not delay treatment for 3-6 months as older guidelines suggested 2

Drug Class Selection

The four major first-line drug classes are equally acceptable 1:

• ACE inhibitors or ARBs (RAS blockers)
• Dihydropyridine calcium channel blockers
• Thiazide or thiazide-like diuretics
• Chlorthalidone is preferred over hydrochlorothiazide due to longer half-life and superior cardiovascular outcomes data 1, 2

Special Population Considerations

Black Patients

• Initial therapy should include a thiazide-like diuretic + calcium channel blocker, or calcium channel blocker + ARB 1, 2
• Avoid ACE inhibitor monotherapy due to reduced response 2

Patients with Diabetes

• ACE inhibitors or ARBs are preferred first-line agents 1, 4
• Target BP <130/80 mmHg 4
• Multiple drugs are typically required to achieve target 1, 4

Women of Childbearing Potential

• Absolutely avoid: ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors due to fetal injury and death risk 2, 4
• Use calcium channel blockers or methyldopa instead 2

Blood Pressure Targets

• General target: <130/80 mmHg for most adults under 65 years 1, 5
• Adults ≥65 years: Systolic BP <130 mmHg if tolerated 1
• Optimal target when tolerated: 120-129 mmHg systolic for most adults 1, 2, 4

Lifestyle Modifications (Concurrent with Medications)

Implement these evidence-based interventions simultaneously with pharmacotherapy 2, 5:

• DASH dietary pattern: 8-10 servings of fruits/vegetables daily, 2-3 servings of low-fat dairy 2
• Sodium restriction: <2,300 mg/day 2
• Weight loss if overweight (BMI >25 kg/m²) 2
• Physical activity: ≥150 minutes of moderate-intensity aerobic activity per week 2, 4
• Alcohol moderation: ≤2 drinks/day for men, ≤1 drink/day for women 2
• Smoking cessation 2

Monitoring and Follow-Up

Initial Laboratory Assessment

• Obtain baseline serum creatinine/eGFR, potassium, and sodium before starting ACE inhibitors, ARBs, or diuretics 2, 4
• Recheck laboratory values 7-14 days after initiation to assess for hyperkalemia or acute kidney injury 2, 4

Follow-Up Schedule

• Recheck BP in 1 month after initiating therapy 1, 2
• Continue follow-up every 1-3 months until BP is controlled 2
• Once controlled, monitor at least annually 4

Titration Strategy

If BP Not Controlled on Two Drugs

• Escalate to triple-combination therapy: ACE inhibitor/ARB + calcium channel blocker + thiazide-like diuretic 1, 2
• Preferably use single-pill combination for the triple therapy 1
• Achieve BP control within 3 months of treatment initiation 2

Resistant Hypertension (BP Uncontrolled on Three Drugs)

• Add spironolactone 25 mg daily as fourth-line agent 1, 2
• If spironolactone not tolerated, consider eplerenone, beta-blockers, or other agents 1
• Refer to hypertension specialist 1

Critical Pitfalls to Avoid

• Never combine ACE inhibitors with ARBs—this increases adverse events without cardiovascular benefit 2, 4
• Never delay pharmacotherapy for lifestyle modification trial when BP ≥140/90 mmHg 2
• Avoid hydrochlorothiazide when chlorthalidone or indapamide are available 2
• Do not use beta-blockers as initial therapy unless specific indication exists (heart failure, coronary disease, post-MI) 1, 2
• Failure to monitor renal function and potassium when using RAS blockers can lead to dangerous hyperkalemia 2, 4
• Assess medication adherence before escalating therapy or diagnosing resistant hypertension 1
• Rule out white coat hypertension with home or ambulatory BP monitoring before intensifying treatment 1