What are the first-line therapies for hypertension?

First-Line Therapy for Hypertension

Thiazide diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are the recommended first-line medications for hypertension management, with thiazide diuretics being the preferred initial choice for most patients. 1, 2, 3

Initial Medication Selection

• Thiazide or thiazide-like diuretics (especially chlorthalidone) are preferred first-line agents due to their proven efficacy in reducing cardiovascular morbidity and mortality 1, 4, 5
• Calcium channel blockers, ACE inhibitors, and ARBs are also effective first-line options with demonstrated cardiovascular benefits 1, 2
• For patients with blood pressure ≥160/100 mmHg, initiation with two antihypertensive medications from different classes is recommended 1, 2
• For patients with blood pressure between 130/80 mmHg and 160/100 mmHg, starting with a single agent may be appropriate 1

Patient-Specific Considerations

• In Black patients, thiazide diuretics and calcium channel blockers are more effective as first-line therapy compared to ACE inhibitors or ARBs 1, 2
• For patients with diabetes and established coronary artery disease, ACE inhibitors or ARBs are recommended as first-line therapy 1, 2
• For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), ACE inhibitors or ARBs should be used as first-line agents to reduce the risk of progressive kidney disease 1
• In elderly patients (≥60 years), thiazide diuretics, calcium channel blockers, ARBs, and ACE inhibitors are all appropriate first-line options 1

Combination Therapy Approach

• Most patients will require multiple drugs to achieve blood pressure control targets 1, 6
• Logical combinations include: (ACE inhibitor or ARB) + (thiazide diuretic or calcium channel blocker) 1, 7
• When three drugs are needed, the combination of an ACE inhibitor or ARB + calcium channel blocker + thiazide diuretic is recommended 1
• Avoid combining ACE inhibitors with ARBs due to increased risk of adverse effects without additional benefit 1

Evidence on Comparative Effectiveness

• The ALLHAT trial demonstrated that chlorthalidone (a thiazide diuretic) was as effective as amlodipine (a CCB) and lisinopril (an ACE inhibitor) in preventing the primary outcome of fatal CHD or nonfatal myocardial infarction 5
• Chlorthalidone was superior to amlodipine in preventing heart failure and superior to lisinopril in preventing stroke and heart failure 5
• Thiazide diuretics, particularly chlorthalidone at 25 mg, have been shown to be more potent than hydrochlorothiazide at 50 mg, especially for overnight blood pressure reduction 8

Management of Resistant Hypertension

• Resistant hypertension is defined as BP ≥140/90 mmHg despite treatment with three antihypertensive drugs including a diuretic 1, 2
• For resistant hypertension, adding a mineralocorticoid receptor antagonist (spironolactone) to the existing regimen is recommended 1, 9

Common Pitfalls and Considerations

• Thiazide diuretics can cause metabolic abnormalities including hyperglycemia, hypokalemia, and hyperuricemia, but these do not reduce their efficacy in preventing cardiovascular events 4, 8
• Beta-blockers are not recommended as first-line therapy for uncomplicated hypertension but are indicated in patients with prior MI, active angina, or heart failure with reduced ejection fraction 1
• Monitoring for adverse effects is essential, particularly electrolyte abnormalities with diuretics and cough with ACE inhibitors 8
• Single-pill combinations can improve medication adherence and should be considered when multiple drugs are needed 2, 7