First-Line Antihypertensive Medications
The recommended first-line antihypertensive medications include thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). 1, 2
First-Line Medication Options
- Thiazide and thiazide-like diuretics (e.g., chlorthalidone) are effective first-line agents with strong evidence for reducing cardiovascular events and heart failure 1, 3
- ACE inhibitors are recommended particularly for patients with diabetes, coronary artery disease, heart failure, or chronic kidney disease with albuminuria 1, 2
- ARBs provide similar benefits to ACE inhibitors and are excellent alternatives for patients who experience ACE inhibitor-induced cough 1, 4
- Long-acting dihydropyridine calcium channel blockers are effective first-line agents, especially for elderly patients and Black patients 1, 2
Population-Specific Recommendations
- For Black patients without heart failure or chronic kidney disease, thiazide diuretics or calcium channel blockers are preferred first-line agents due to greater efficacy 2, 1
- For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), ACE inhibitors or ARBs are recommended as initial therapy to reduce risk of progressive kidney disease 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 heart failure, ACE inhibitors, ARBs, or beta-blockers are preferred initial agents 1, 2
Comparative Effectiveness
- Thiazide diuretics have been shown to be superior to calcium channel blockers for prevention of heart failure 2, 3
- Thiazide diuretics are superior to alpha-blockers in preventing cardiovascular events (ARR 3.1%) and heart failure (ARR 2.6%) 3
- ACE inhibitors are less effective than thiazide diuretics and calcium channel blockers in Black patients for prevention of stroke and heart failure 2
- Beta-blockers are not recommended as first-line therapy for uncomplicated hypertension due to lower effectiveness, especially for stroke prevention in older adults 2
Initial Treatment Strategy
- For Stage 1 hypertension (130-139/80-89 mmHg), start with a single antihypertensive medication 2
- For Stage 2 hypertension (≥140/90 mmHg), consider initiating treatment with two first-line agents of different classes, either as separate agents or in a fixed-dose combination 1, 2
- Combination therapy is often necessary to achieve blood pressure targets, and fixed-dose combinations in a single pill can improve adherence 5
Important Monitoring Considerations
- When using ACE inhibitors, ARBs, or diuretics, monitor serum creatinine, eGFR, and potassium levels within 7-14 days after initiation and at least annually 2
- Avoid combining ACE inhibitors and ARBs due to increased risk of hyperkalemia and acute kidney injury without added benefit 1, 2
- For patients with severely reduced eGFRs (<30 mL/min/1.73 m²), medication selection requires special consideration, though thiazide-like diuretics may still be effective 1
Common Pitfalls to Avoid
- Alpha-blockers (e.g., doxazosin) are not recommended as first-line therapy due to inferior outcomes compared to thiazide diuretics, including doubled risk of heart failure 1, 2
- Simultaneous use of an ACE inhibitor, ARB, and/or renin inhibitor is potentially harmful and should be avoided 1
- Beta-blockers are not included as first-line agents for uncomplicated hypertension because they are less effective for cardiovascular disease prevention and stroke protection than diuretics or CCBs 1, 2
Dosing Considerations
- Losartan typically starts at 50 mg once daily, with possible increase to 100 mg daily as needed 4
- For patients with possible intravascular depletion (e.g., on diuretic therapy), a lower starting dose of 25 mg is recommended 4
- Chlorthalidone is often preferred over hydrochlorothiazide due to its longer duration of action and stronger evidence in clinical trials 1, 6