What is the initial treatment for a newly diagnosed adult with primary hypertension and no compelling contraindications?

Initial Treatment for Hypertension

For a newly diagnosed adult with primary hypertension and no compelling contraindications, initiate pharmacologic therapy with a single first-line antihypertensive agent—either a thiazide-like diuretic (chlorthalidone preferred), an ACE inhibitor, an ARB, or a dihydropyridine calcium channel blocker—combined simultaneously with comprehensive lifestyle modifications. 1

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Confirming the Diagnosis Before Treatment

• Verify elevated office readings with out-of-office measurements (home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg) to exclude white-coat hypertension before starting therapy. 1
• Obtain at least two readings on each of three separate occasions using proper technique (seated, back supported, feet flat, arm at heart level, appropriate cuff size, after 5 minutes of rest). 1

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Blood Pressure Thresholds and Treatment Intensity

Stage 1 Hypertension (130–139/80–89 mmHg)

• Low cardiovascular risk (<10% 10-year ASCVD risk): Begin with lifestyle modifications alone; reassess in 3–6 months and start medication only if BP remains elevated. 1
• High cardiovascular risk (≥10% 10-year ASCVD risk): Initiate single-agent pharmacotherapy immediately alongside lifestyle changes; reassess in 1 month. 1

Stage 2 Hypertension (≥140/90 mmHg)

• Start dual-agent combination therapy from two different classes at the same visit, preferably as a single-pill combination, to achieve faster control and improve adherence. 2, 1
• For BP ≥160/100 mmHg, consider initiating two agents at full doses immediately. 1

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First-Line Medication Selection

Non-Black Patients Without Specific Comorbidities

• Preferred initial agents: ACE inhibitor, ARB, thiazide-like diuretic (chlorthalidone preferred over hydrochlorothiazide), or dihydropyridine calcium channel blocker—all have comparable efficacy for cardiovascular outcomes. 2, 1
• For dual therapy in stage 2 hypertension, combine any two of these classes (e.g., ACE inhibitor + calcium channel blocker, ACE inhibitor + thiazide, or calcium channel blocker + thiazide). 2, 1

Black Patients Without Specific Comorbidities

• Preferred regimen: Calcium channel blocker + thiazide-like diuretic, which provides superior BP reduction compared with ACE inhibitor/ARB monotherapy due to lower renin activity in this population. 2, 1
• ACE inhibitors or ARBs may be added when combined with other agents. 1

Comorbidity-Specific Choices

• Chronic kidney disease or albuminuria (≥30 mg/g): ACE inhibitor or ARB is mandatory as initial therapy to slow kidney disease progression. 2, 1
• Coronary artery disease: ACE inhibitor or ARB preferred; add a beta-blocker if prior MI or angina. 2, 1
• Heart failure with reduced ejection fraction: Use guideline-directed medical therapy beta-blockers (carvedilol, metoprolol succinate, or bisoprolol), ACE inhibitors/ARBs, and mineralocorticoid receptor antagonists. 2
• Diabetes mellitus: ACE inhibitor or ARB preferred. 1

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Specific Dosing Recommendations

Thiazide-Like Diuretics

• Chlorthalidone 12.5–25 mg once daily is preferred over hydrochlorothiazide due to longer duration of action (24–72 hours vs. 6–12 hours) and superior cardiovascular outcome data from ALLHAT. 2, 3
• Hydrochlorothiazide 25 mg daily may be used if chlorthalidone is unavailable, but it is less effective. 2
• Check serum potassium and creatinine 2–4 weeks after initiation to detect hypokalemia or renal function changes. 2, 1

ACE Inhibitors

• Lisinopril 10 mg once daily is an appropriate starting dose; titrate to 20–40 mg daily if needed. 1
• Monitor serum potassium and creatinine 7–14 days after initiation, especially when combined with other renally active agents. 1

Calcium Channel Blockers

• Amlodipine 5 mg once daily, titrating to 10 mg if needed after 2–4 weeks. 2, 1

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Blood Pressure Targets

• Primary target for most adults <65 years: <130/80 mmHg. 1
• For adults ≥65 years: Systolic <130 mmHg if tolerated. 1
• Minimum acceptable target for all patients: <140/90 mmHg. 2, 1
• High-risk groups (diabetes, CKD, established CVD): Aim for <130/80 mmHg. 1

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Lifestyle Modifications (Essential for All Patients)

Intervention	Expected BP Reduction	Key Details
Sodium restriction	5–10 mmHg systolic	Limit to <2 g/day (≈5 g salt); enhances efficacy of all antihypertensive classes, especially diuretics and ACE inhibitors/ARBs [1,4]
DASH diet	~11/5.5 mmHg	8–10 servings fruits/vegetables, 2–3 servings low-fat dairy, whole grains, reduced saturated fat [1,4]
Weight loss	~6/5 mmHg per 10 kg	Target BMI 20–25 kg/m² [1,4]
Regular exercise	~4/3 mmHg	≥150 minutes/week moderate-intensity aerobic activity [1,4]
Alcohol moderation	2–4 mmHg	≤2 drinks/day for men, ≤1 drink/day for women [1,4]
Smoking cessation	Variable	Mandatory for all patients; reduces overall cardiovascular risk [1,5]

• Combination of two or more lifestyle modifications may have additive benefit, potentially reducing the need for medications or allowing lower doses. 6, 4, 7

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Titration and Escalation Strategy

1. Goal is to reach target BP within 3 months. 1
2. If BP not at goal on a single agent after 4 weeks, add a second agent from a different class (e.g., ACE inhibitor + calcium channel blocker or ACE inhibitor + thiazide). 2, 1
3. If still uncontrolled on two agents, add a third agent to form the standard triple regimen (ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic). 2, 1
4. For apparent resistant hypertension (uncontrolled on three drugs including a diuretic), first verify adherence, then switch to chlorthalidone if not already used and add spironolactone 25–50 mg daily (expected additional reduction ≈20/10 mmHg). 2, 1

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Monitoring After Medication Initiation

• Re-measure office BP 2–4 weeks after any medication change. 2, 1
• Check serum creatinine/eGFR and electrolytes 7–14 days after starting an ACE inhibitor, ARB, or diuretic. 1
• Follow up every 1–3 months until BP is controlled, then every 3–6 months. 1

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Critical Pitfalls to Avoid

• Do not postpone pharmacotherapy in patients with BP ≥140/90 mmHg; start medications concurrently with lifestyle changes rather than waiting 3–6 months for lifestyle modification alone. 1
• Avoid monotherapy for stage 2 hypertension (≥140/90 mmHg); dual therapy is required for faster control. 2, 1
• Do not combine an ACE inhibitor with an ARB due to increased risk of hyperkalemia and acute kidney injury without added cardiovascular benefit. 2, 1
• Reserve beta-blockers for compelling indications (post-MI, heart failure with reduced ejection fraction, angina, atrial fibrillation requiring rate control); they are less effective than other first-line classes for stroke prevention in uncomplicated hypertension. 2, 1
• Confirm medication adherence before labeling treatment as failure; non-adherence is the most common cause of apparent treatment resistance. 2, 1
• Exclude white-coat hypertension with out-of-office monitoring before initiating therapy in low-risk patients. 1
• Prefer chlorthalidone over hydrochlorothiazide when available for superior 24-hour BP control and cardiovascular outcomes. 2, 3
• Do not delay treatment intensification when BP remains ≥140/90 mmHg after 4 weeks; prompt action within 2–4 weeks is required to reduce cardiovascular risk. 2, 1