What is the first-line medication for hypertension (HTN)?

First-Line Medication for Hypertension

Thiazide diuretics are the recommended first-line medication for hypertension treatment based on the strongest evidence for preventing cardiovascular disease outcomes. 1

Initial Medication Selection

• Thiazide or thiazide-like diuretics (especially chlorthalidone) have the strongest evidence for prevention of cardiovascular events and are particularly effective for preventing heart failure 1, 2
• The ALLHAT study demonstrated that diuretics were equally effective in primary outcomes or, in some instances, superior in comparison with secondary end points versus calcium antagonists, ACE inhibitors, and α-blockers 3
• Other first-line options include:
  • Calcium Channel Blockers (CCBs) - effective alternatives when thiazides cannot be used 1, 2
  • ACE Inhibitors or ARBs - effective for BP reduction, particularly beneficial in specific comorbidities 1, 2

Population-Specific Considerations

• For Black patients, thiazide diuretics or CCBs are preferred first-line agents due to greater efficacy 1, 2
• For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), ACE inhibitors or ARBs are recommended as first-line therapy 1, 2
• For patients with established coronary artery disease, ACE inhibitors or ARBs are recommended first-line 1
• For patients aged 55 or older, calcium channel blockers or diuretics are generally more effective first-line agents 1
• For patients younger than 55 and white, ACE inhibitors or ARBs may be more effective as initial treatment 1

Monotherapy vs. Combination Therapy

• For Stage 1 hypertension (130-139/80-89 mmHg), single-agent therapy is reasonable 1, 4
• For Stage 2 hypertension (≥140/90 mmHg), initial treatment with two antihypertensive medications is recommended 1, 2
• For BP ≥160/100 mmHg or >20/10 mmHg above target, start with two-drug combination 1, 5
• Single-pill combinations may improve medication adherence 1, 2

Evidence Supporting Thiazide Diuretics as First-Line

• The ALLHAT study showed that diuretics were more effective than calcium antagonists and ACE inhibitors in preventing heart failure 3
• Low-dose diuretics have been shown to be more effective as first-line treatment for preventing heart failure compared to ACE inhibitors, beta-blockers, or calcium channel blockers 1
• Diuretics have demonstrated effectiveness across diverse patient populations, including elderly, young, men, women, Black, non-Black, diabetic, and non-diabetic patients 3

Common Pitfalls and Caveats

• Beta-blockers are not recommended as first-line therapy unless there are specific indications (prior MI, active angina, heart failure with reduced ejection fraction) 1, 2
• Alpha-blockers should not be used as first-line therapy due to inferior cardiovascular protection compared to other agents 3, 1
• The combination of two RAS blockers (ACE inhibitors and ARBs) is not recommended due to increased risk of adverse effects without additional benefit 1, 2
• For resistant hypertension, spironolactone should be considered as a fourth agent 2

Medication Efficacy Considerations

• Calcium channel blockers like amlodipine are effective for hypertension treatment and have been shown to reduce the risk of fatal and nonfatal cardiovascular events 6
• ACE inhibitors like lisinopril are indicated for hypertension treatment and have demonstrated effectiveness in lowering blood pressure 7
• Recent evidence suggests that a combination of amlodipine and an ACE inhibitor/ARB can achieve superior blood pressure control compared to monotherapy in patients with stage 2 hypertension 5