What is the recommended initial antihypertensive treatment for an adult outpatient with hypertension, without severe hypertension or compelling indications?

Initial Antihypertensive Outpatient Treatment

For adults with uncomplicated hypertension, initiate treatment with a thiazide-type diuretic (preferably chlorthalidone 12.5-25 mg daily) as first-line monotherapy for Stage 1 hypertension, or combination therapy with two agents from different classes for Stage 2 hypertension. 1, 2

Treatment Initiation Based on Blood Pressure Stage

Stage 1 Hypertension (130-139/80-89 mm Hg)

• Start with single-agent therapy and titrate dosage before adding sequential agents 1, 2
• Initiate pharmacotherapy if the patient has established cardiovascular disease, diabetes, chronic kidney disease, or 10-year ASCVD risk ≥10% 2
• For patients without these risk factors, lifestyle modifications alone may be attempted for 3-6 months before initiating medication 1, 3

Stage 2 Hypertension (≥140/90 mm Hg)

• Initiate combination therapy with two first-line agents from different classes, preferably as a single-pill combination 1, 2
• This approach is particularly important when BP is >20/10 mm Hg above target 1
• However, use caution in older patients due to risk of hypotension or orthostatic hypotension; monitor BP carefully 1

First-Line Medication Selection

Preferred Initial Agent: Thiazide-Type Diuretics

Chlorthalidone 12.5-25 mg once daily is the optimal first-choice agent based on the strongest evidence from randomized controlled trials, particularly the ALLHAT trial 1, 2

• Thiazide diuretics have superior outcomes compared to other classes for stroke prevention and heart failure prevention 1, 2
• Chlorthalidone is preferred over hydrochlorothiazide due to longer half-life and more cardiovascular outcome data 2, 4
• In network meta-analyses, diuretics were significantly more effective than beta blockers for stroke and cardiovascular events, and better than calcium channel blockers for heart failure prevention 1

Alternative First-Line Options

Calcium Channel Blockers (CCBs):

• Amlodipine 5-10 mg once daily is equally effective as thiazides for all cardiovascular events except heart failure 2
• Consider as first-line if thiazide diuretics are not tolerated 2

ACE Inhibitors:

• Lisinopril 10-40 mg once daily is effective first-line therapy 2, 5
• Particularly appropriate for patients with albuminuria or established coronary artery disease 2

Angiotensin Receptor Blockers (ARBs):

• Losartan 50-100 mg once daily is equally effective to ACE inhibitors 2, 6
• Useful alternative if ACE inhibitors cause cough 2

Beta Blockers: Not Recommended as First-Line

• Beta blockers were significantly less effective than diuretics for prevention of stroke and cardiovascular events in systematic reviews 1
• Should be reserved for specific cardiac indications (post-MI, heart failure, coronary disease) rather than uncomplicated hypertension 1

Special Population Considerations

Black Patients Without Heart Failure or CKD

Initial treatment should include a thiazide diuretic or calcium channel blocker 1, 2, 4

• Avoid ACE inhibitors or ARBs as monotherapy in this population, as they are less effective 4
• Most Black patients will require combination therapy to achieve BP control 4
• Chlorthalidone 12.5-25 mg daily or amlodipine 5-10 mg daily are preferred initial agents 4

Patients with Diabetes

• All four first-line classes (thiazides, CCBs, ACE inhibitors, ARBs) are equally effective 2
• Consider ACE inhibitor or ARB if albuminuria is present 2

Patients with Chronic Kidney Disease or Albuminuria

ACE inhibitor or ARB is mandatory first-line therapy to reduce progressive kidney disease 2

Combination Therapy Strategy

When two agents are needed, preferred combinations include: 1, 2

• ACE inhibitor or ARB + CCB
• ACE inhibitor or ARB + thiazide diuretic
• CCB + thiazide diuretic

Never combine ACE inhibitors with ARBs due to increased risk of adverse events without additional benefit 1

Single-pill combinations improve adherence but may contain suboptimal doses of the thiazide component; verify adequate diuretic dosing 1

Blood Pressure Targets

• General target: <130/80 mm Hg for most adults with hypertension 1, 2
• Minimum acceptable control (audit standard): <150/90 mm Hg 1
• For adults ≥65 years: SBP <130 mm Hg 7

Lifestyle Modifications

All patients should receive lifestyle counseling regardless of medication initiation: 1, 3, 7

• Weight reduction to ideal body weight (most effective intervention) 3, 8
• DASH diet (dietary approaches to stop hypertension) - considered most effective dietary intervention 3
• Sodium restriction to <2.3 g/day; ideally <1.5 g/day 3, 7
• Potassium supplementation (unless contraindicated) 7
• Physical activity: 150 minutes/week of moderate-intensity aerobic exercise 3, 7
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 3, 7
• Smoking cessation 8

Lifestyle modifications enhance the efficacy of pharmacologic therapy and may reduce the number or dose of medications required 3, 8

Follow-Up and Monitoring

• Reassess monthly after medication initiation or changes until target BP is achieved 2
• Once BP is controlled, follow-up every 3-5 months 2
• Monitor electrolytes and renal function within 7-14 days when starting ACE inhibitors, ARBs, or diuretics, then at least annually 2
• Check standing BP in elderly patients to assess for orthostatic hypotension 2

Common Pitfalls to Avoid

• Do not use beta blockers as first-line therapy in uncomplicated hypertension due to inferior stroke prevention 1
• Avoid rapid BP reduction in hypertensive urgencies (asymptomatic severe hypertension); oral agents are appropriate, not IV medications 1, 9
• Do not use short-acting nifedipine for hypertensive urgencies due to unpredictable BP drops and adverse outcomes 9
• Monitor for orthostatic hypotension when initiating combination therapy in older adults 1
• Approximately 25-50% of patients will require treatment adjustments beyond initial therapy; anticipate this and maintain close follow-up 1