What are the initial medications for managing hypertension?

Initial Antihypertensive Medication Selection

For most adults with hypertension, initial pharmacological treatment should be a thiazide or thiazide-like diuretic (such as hydrochlorothiazide 12.5-25 mg daily or chlorthalidone), an ACE inhibitor (such as lisinopril 10 mg daily), an angiotensin receptor blocker (such as losartan 50 mg daily), or a long-acting dihydropyridine calcium channel blocker (such as amlodipine). 1, 2

Treatment Initiation Based on Blood Pressure Severity

For BP 140-159/90-99 mmHg:

• Start with a single antihypertensive agent from one of the four major drug classes 3, 2
• Select based on patient demographics and comorbidities 2

For BP ≥160/100 mmHg:

• Initiate treatment immediately with two antihypertensive medications, preferably as a single-pill combination 3, 4
• This approach achieves blood pressure control more rapidly and improves adherence 4

Medication Selection by Patient Demographics

Non-Black patients:

• First choice: ACE inhibitor (lisinopril 10 mg daily) or ARB (losartan 50 mg daily) 2, 5, 6

Black patients:

• First choice: Calcium channel blocker or thiazide-like diuretic 2, 4
• May combine with ACE inhibitor or ARB if needed 4

Medication Selection by Comorbidities

Diabetes with albuminuria or chronic kidney disease:

• Mandatory first-line: ACE inhibitor or ARB 3, 2, 4
• Target dose: lisinopril 20-40 mg daily or losartan 50-100 mg daily 2, 5, 6
• Add calcium channel blocker or thiazide-like diuretic if BP goal not achieved 2

Heart failure with reduced ejection fraction:

• ACE inhibitor (lisinopril starting at 5 mg daily) plus diuretic 2, 5
• Add beta-blocker for patients with prior myocardial infarction 2

Coronary artery disease:

• ACE inhibitor or ARB as first choice 2
• Consider adding beta-blocker if prior myocardial infarction 2

Resistant hypertension (BP uncontrolled on 3 drugs):

• Use triple therapy: ACE inhibitor/ARB + calcium channel blocker + thiazide-like diuretic 3, 2
• Add mineralocorticoid receptor antagonist (spironolactone) as fourth agent if necessary 3, 4

Effective Two-Drug Combinations

When combination therapy is needed, the following are well-tolerated and effective 1, 4:

• Thiazide diuretic + ACE inhibitor
• Thiazide diuretic + ARB
• Calcium channel blocker + ACE inhibitor
• Calcium channel blocker + ARB

Single-pill combinations improve medication adherence and should be preferred over separate pills 2, 4

Specific Dosing Guidance

Lisinopril (ACE inhibitor):

• Initial dose: 10 mg once daily 5
• Usual range: 20-40 mg daily 5
• If on diuretics: start with 5 mg daily 5

Losartan (ARB):

• Initial dose: 50 mg once daily 6
• Maximum: 100 mg daily 6
• If volume depleted: start with 25 mg daily 6

Hydrochlorothiazide (thiazide diuretic):

• Initial dose: 12.5-25 mg once daily 7
• Maximum: 50 mg daily (doses above this not recommended) 7

Critical Pitfalls to Avoid

Do NOT combine ACE inhibitors with ARBs - this increases adverse effects without additional benefit 2

Avoid beta-blockers as first-line therapy unless specifically indicated for coronary artery disease, prior MI, or heart failure 3, 2

Do NOT delay drug therapy in high-risk patients (diabetes, chronic kidney disease, cardiovascular disease) or those with BP ≥160/100 mmHg 2

Avoid thiazide + beta-blocker combination in patients with metabolic syndrome or high diabetes risk due to dysmetabolic effects 4

Treatment Targets and Monitoring

Target blood pressure:

• Most adults: <130/80 mmHg 1, 2
• Patients with known cardiovascular disease: <130 mmHg systolic 1
• Elderly patients (≥65 years): individualize based on frailty, aim for 130-139 mmHg systolic if tolerated 2

Monitoring schedule:

• Monthly visits until BP target achieved 4
• For patients on ACE inhibitors, ARBs, or diuretics: monitor serum creatinine/eGFR and potassium at least annually 3, 4
• Aim to achieve target BP within 3 months of initiating therapy 2

Dose Titration Strategy

• Start with one medication at a low dose 2
• Increase the dose or add a second agent if BP goal not achieved after 4 weeks 2
• If adding a diuretic to ACE inhibitor/ARB, may need to reduce initial ACE inhibitor/ARB dose 5