What medication should be started for a patient newly diagnosed with primary hypertension?

Initial Medication Selection for Primary Hypertension

For a patient newly diagnosed with primary hypertension, a thiazide-like diuretic such as chlorthalidone (12.5-25 mg daily) should be the first-line medication choice due to its proven efficacy in reducing cardiovascular morbidity and mortality. 1, 2, 3

Treatment Algorithm Based on Hypertension Severity

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

• If 10-year ASCVD risk <10%: Begin with lifestyle modifications; reassess in 3-6 months
• If 10-year ASCVD risk ≥10%: Start chlorthalidone 12.5 mg daily plus lifestyle modifications; reassess in 1 month

Stage 2 Hypertension (≥140/90 mmHg)

• Start combination therapy with 2 agents from different classes:
  • Chlorthalidone 12.5 mg daily (first agent)
  • Add either an ACE inhibitor or ARB (second agent)
  • Reassess in 1 month

Very High BP (≥180/110 mmHg)

• Immediate evaluation and prompt treatment with combination therapy
• Chlorthalidone plus ACE inhibitor or ARB
• Consider early referral if not controlled quickly

Rationale for Thiazide Diuretic as First Choice

Chlorthalidone is preferred over other antihypertensives based on:

• Proven reduction in all-cause mortality compared to placebo 2
• Superior efficacy in preventing stroke compared to ACE inhibitors 3
• Superior efficacy in preventing heart failure compared to calcium channel blockers 3
• Longer half-life and more consistent 24-hour blood pressure control than hydrochlorothiazide 1
• Cost-effectiveness as first-line therapy 3

The landmark ALLHAT trial demonstrated that chlorthalidone was as effective as amlodipine (calcium channel blocker) and lisinopril (ACE inhibitor) in preventing the primary outcome of fatal CHD or nonfatal myocardial infarction, while being superior in preventing heart failure and stroke 3.

Special Population Considerations

• Patients with diabetes or albuminuria: Consider ACE inhibitor or ARB as first-line 1, 4
• Black patients: Diuretic or calcium channel blocker may be more effective initially 1, 4
• Elderly patients (>80 years): Start with lower doses (chlorthalidone 12.5 mg) and titrate slowly 4
• Patients with possible intravascular depletion: Use caution with diuretics; consider starting with lower doses 5

Monitoring After Initiation

• Check electrolytes and renal function 2-4 weeks after starting therapy 1
• Monitor for hyponatremia, hypokalemia, elevated uric acid and calcium levels with thiazide diuretics 1
• Assess for orthostatic hypotension, especially in elderly patients 4
• Schedule follow-up based on hypertension severity and initial response

Common Pitfalls to Avoid

• Inadequate dosing: Starting with too low a dose may delay achieving blood pressure control
• Failure to assess for secondary causes: Consider secondary hypertension if onset before age 30, resistant hypertension, or acute rise in previously stable BP 6
• Inappropriate combinations: Avoid combining ACE inhibitors with ARBs or direct renin inhibitors 1
• Medication inertia: Failure to titrate or add medications when BP remains uncontrolled
• Ignoring adherence issues: Single daily dosing regimens improve compliance

Remember that while initial medication choice is important, achieving target blood pressure is the ultimate goal. If the first medication is ineffective or poorly tolerated, prompt adjustment of therapy is essential to reduce cardiovascular risk.