What is the best initial medication for hypertension (high blood pressure)?

First-Line Medication for Hypertension

The best initial medication for hypertension is a thiazide or thiazide-like diuretic, which should be used as first-line therapy for most patients with uncomplicated hypertension, either alone or in combination with other agents. 1

Initial Medication Selection Algorithm

First-line options (any of these classes can be used initially):

• Thiazide or thiazide-like diuretics (preferred for most patients) 1
• ACE inhibitors (angiotensin-converting enzyme inhibitors) 1
• ARBs (angiotensin receptor blockers) 1
• Dihydropyridine calcium channel blockers 1

Patient-specific considerations:

1. For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g):

   • Initial treatment should include an ACE inhibitor or ARB 1

2. For patients with established coronary artery disease:

   • ACE inhibitors or ARBs are recommended first-line 1

3. For patients with severe hypertension (≥160/100 mmHg):

   • Begin with two-drug combination therapy (usually including a thiazide diuretic) 1

4. For Black patients:

   • Thiazide diuretics or calcium channel blockers are more effective than ACE inhibitors 1

Evidence Supporting Thiazide Diuretics as First-Line

Thiazide diuretics have consistently demonstrated effectiveness in reducing cardiovascular events in hypertensive patients 1. In the largest head-to-head comparison of first-step drug therapy, the thiazide-like diuretic chlorthalidone was superior to both calcium channel blockers and ACE inhibitors in preventing heart failure 1.

Key advantages of thiazide diuretics include:

• Proven efficacy in reducing cardiovascular events 1
• Enhanced antihypertensive efficacy when combined with other medications 1
• More affordable than many other antihypertensive agents 1
• Particularly effective in Black patients 1

Combination Therapy Considerations

• For patients with BP between 130/80 mmHg and 160/100 mmHg, starting with a single agent is reasonable 1
• For patients with BP ≥160/100 mmHg, initial treatment with two antihypertensive medications is recommended 1
• Single-pill combinations may improve medication adherence 1

Common Pitfalls and Caveats

• Beta-blockers are not recommended as first-line therapy unless there are specific indications such as prior myocardial infarction, active angina, or heart failure with reduced ejection fraction 1
• Alpha-blockers are not recommended as first-line agents as they are less effective for prevention of cardiovascular disease than other first-step agents 1
• Bedtime dosing of antihypertensive medications is not specifically recommended over morning dosing 1
• Monitoring for side effects is essential, particularly:
  • Electrolyte abnormalities with diuretics 1
  • Hyperkalemia with ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists 1
  • Cough with ACE inhibitors (ARBs may be better tolerated) 1

Dosing Considerations

• ACE inhibitors (e.g., lisinopril): Usually start at 10 mg once daily, with typical dosage range of 20-40 mg per day 2
• ARBs (e.g., losartan): Usually start at 50 mg once daily, can be increased to maximum of 100 mg once daily as needed 3
• Lower starting doses should be considered for patients who are elderly, volume depleted, or on diuretic therapy 2, 3

Lifestyle Modifications

While pharmacotherapy is important, all patients with hypertension should implement lifestyle modifications including:

• Weight loss if indicated 1
• DASH (Dietary Approaches to Stop Hypertension) eating pattern 1
• Sodium reduction and potassium supplementation 4
• Physical activity 1
• Limited alcohol consumption 1, 4