What is the recommended initial treatment for an adult patient with primary hypertension, considering their individual characteristics and potential comorbidities such as diabetes, kidney disease, or heart failure?

Initial Antihypertensive Treatment for Primary Hypertension

For most adults with primary hypertension, initiate treatment with a thiazide-type diuretic (preferably chlorthalidone 12.5-25 mg daily), an ACE inhibitor, an ARB, or a long-acting dihydropyridine calcium channel blocker, with the specific choice guided by blood pressure severity, comorbidities, and race. 1, 2

Blood Pressure Thresholds for Starting Medication

• Start pharmacotherapy immediately for any patient with confirmed BP ≥140/90 mmHg 1, 2
• Start pharmacotherapy for BP 130-139/80-89 mmHg in patients with any of the following high-risk features: 1, 2
  • Existing cardiovascular disease (prior MI, stroke, heart failure)
  • 10-year ASCVD risk ≥10%
  • Diabetes mellitus
  • Chronic kidney disease
  • Age ≥65 years
• For BP 130-139/80-89 mmHg without these risk factors, attempt lifestyle modification for up to 3 months before adding medication 1

First-Line Medication Selection Algorithm

Step 1: Determine if Monotherapy or Combination Therapy

• Use combination therapy (two drugs from different classes) if: 1, 2

  • BP ≥150/90 mmHg or Stage 2 hypertension (≥140/90 mmHg)
  • Preferably use single-pill combinations to improve adherence 1, 2

• Use monotherapy if: 1, 2

  • BP 130-139/80-89 mmHg in high-risk patients
  • Stage 1 hypertension (130-139/80-89 mmHg)

Step 2: Select Drug Class Based on Patient Characteristics

For Black Adults Without Heart Failure or CKD:

• Start with thiazide-type diuretic OR calcium channel blocker 1, 2
• ACE inhibitors and ARBs are less effective as monotherapy in this population 2, 3

For Patients With Diabetes:

• If albuminuria present: ACE inhibitor or ARB as first-line 1, 2
• If no albuminuria: Any of the four first-line classes (thiazide diuretic, ACE inhibitor, ARB, or calcium channel blocker) 1, 2

For Patients With Chronic Kidney Disease:

• ACE inhibitor or ARB as first-line therapy 1, 2, 3
• Monitor serum creatinine and potassium 2-4 weeks after initiation 1

For Patients With Heart Failure:

• ACE inhibitor or ARB plus diuretic 1, 2
• Beta-blockers are indicated for specific cardiac conditions 1

For Patients With Thoracic Aortic Disease:

• Beta-blocker as preferred first-line agent 1

For All Other Patients (No Compelling Indications):

• Thiazide-type diuretic (chlorthalidone preferred), ACE inhibitor, ARB, or long-acting dihydropyridine calcium channel blocker 1, 2
• Chlorthalidone has the strongest evidence base from trials involving >50,000 patients 4

Step 3: Specific Drug Dosing

Thiazide Diuretics (Preferred First Choice for Most):

• Chlorthalidone 12.5-25 mg once daily (preferred due to longer half-life and proven CVD reduction) 1, 4
• Hydrochlorothiazide 25-50 mg once daily (if chlorthalidone unavailable) 1, 4
• Monitor for hypokalemia, hyponatremia, hyperuricemia, and hyperglycemia 1

ACE Inhibitors:

• Lisinopril 10 mg once daily initially, titrate to 20-40 mg daily 1, 5
• Start with 5 mg once daily if patient is on diuretic 5
• Monitor serum creatinine and potassium 2-4 weeks after initiation 1
• Do not combine with ARBs (increases adverse events without benefit) 1, 3

ARBs (Alternative to ACE Inhibitors):

• Losartan 50-100 mg once daily, Irbesartan 150-300 mg once daily, or equivalent 1
• Use if ACE inhibitor causes intolerable cough 3, 6
• ARBs have lower withdrawal rates due to adverse effects compared to ACE inhibitors 7, 6

Calcium Channel Blockers:

• Amlodipine 5-10 mg once daily 1
• Long-acting dihydropyridines preferred 1

Combination Therapy Strategies

Preferred two-drug combinations: 1, 2

• ACE inhibitor or ARB + thiazide diuretic
• ACE inhibitor or ARB + calcium channel blocker
• Calcium channel blocker + thiazide diuretic

If triple therapy needed: 1

• ACE inhibitor or ARB + calcium channel blocker + thiazide diuretic (preferably as single-pill combination)

If still uncontrolled on triple therapy: 1

• Add spironolactone, alpha-blocker, or beta-blocker
• Consider referral to hypertension specialist

Blood Pressure Targets

• General target: <130/80 mmHg for most adults <65 years 1, 2
• For adults ≥65 years: <130 mmHg systolic if tolerated and ambulatory 1
• For patients with existing CVD: <130 mmHg systolic 1, 2
• Initial target for all patients: <140/90 mmHg, then tighten to <130/80 mmHg if tolerated 1

Monitoring Schedule

• Reassess BP in 1 month after initiating pharmacotherapy or making dose changes 1, 2
• Check electrolytes and renal function 2-4 weeks after starting ACE inhibitor, ARB, or diuretic 1
• Once BP target achieved, follow-up every 3-6 months 1
• Aim to achieve BP control within 3 months of starting treatment 1

Critical Pitfalls to Avoid

• Never combine ACE inhibitor with ARB (increases hyperkalemia and acute kidney injury without cardiovascular benefit) 1, 3
• Do not use beta-blockers as first-line unless specific cardiac indication (less effective for stroke prevention) 1, 2
• Avoid underdosing medications before adding additional agents—titrate to maximum tolerated dose first 2
• Do not delay treatment for extensive laboratory testing in patients with BP ≥140/90 mmHg 1
• Monitor for orthostatic hypotension in older adults and those with diabetes 1
• Check potassium within 2-4 weeks when using ACE inhibitors or ARBs, especially in patients with CKD 1