What is the first drug of choice for initial management of hypertension?

First Drug of Choice for Hypertension

For uncomplicated hypertension in most adults, initiate treatment with a thiazide or thiazide-like diuretic, specifically chlorthalidone 12.5-25 mg once daily, which has the strongest evidence for reducing cardiovascular mortality, heart failure, and stroke compared to other drug classes. 1

Treatment Algorithm by Patient Characteristics

For Most Adults Without Comorbidities

• Start with chlorthalidone as the optimal thiazide diuretic based on superior cardiovascular outcomes data and longer duration of action, providing better 24-hour blood pressure control particularly overnight 1, 2
• Chlorthalidone demonstrated superiority over lisinopril in preventing stroke and over amlodipine in preventing heart failure in the landmark ALLHAT trial 1, 2
• An SBP reduction of 10 mmHg with thiazide therapy decreases cardiovascular events by approximately 20-30% 3
• If chlorthalidone is unavailable, hydrochlorothiazide 12.5-25 mg once daily is an acceptable alternative, though less potent 1

For Black Patients Without Comorbidities

• Initiate with either a thiazide diuretic or calcium channel blocker (amlodipine) as first-line therapy 1
• ACE inhibitors are notably less effective than calcium channel blockers and thiazides for stroke and heart failure prevention in Black patients 1
• Amlodipine is particularly effective in this population for preventing heart failure and stroke 4

For Patients With Diabetes

• ACE inhibitors are the reasonable first-line choice for most diabetic patients 5
• For diabetic patients with microalbuminuria (≥30 mg/g) or clinical nephropathy, ACE inhibitors (type 1 and type 2) or ARBs (type 2) are considered first-line therapy to prevent progression of kidney disease 5, 1
• For diabetic patients with established coronary artery disease, ACE inhibitors or ARBs are recommended as first-line therapy 4, 1
• However, diuretic and beta-blocker-based therapy are also supported by evidence in diabetic patients 5

For Patients With Albuminuria

• Start with an ACE inhibitor or ARB when urine albumin-to-creatinine ratio is ≥30 mg/g 4, 1
• Monitor serum creatinine/eGFR and potassium within 7-14 days after initiation and at least annually 1

Staging-Based Approach

Stage 1 Hypertension (SBP 130-139 or DBP 80-89 mmHg)

• Initiate with single-agent therapy and titrate dosage before adding sequential agents 1
• Target blood pressure <130/80 mmHg for adults <65 years 3

Stage 2 Hypertension (SBP ≥140 or DBP ≥90 mmHg)

• Initiate with two first-line agents of different classes, either as separate medications or fixed-dose combination 1, 3
• This applies when blood pressure is ≥20/10 mmHg above goal 1

Alternative First-Line Options

When Thiazides Cannot Be Used

• Amlodipine (long-acting dihydropyridine calcium channel blocker) is an appropriate alternative, offering effective 24-hour blood pressure control with once-daily dosing 4
• The ALLHAT study demonstrated amlodipine was equally effective as chlorthalidone in preventing coronary heart disease mortality and morbidity 4
• ACE inhibitors (captopril, lisinopril, or ramipril) are better choices than calcium channel blockers when diuretics cannot be used 2

Acceptable First-Line Classes

• Thiazide or thiazide-like diuretics (preferred) 1, 3
• ACE inhibitors 1, 3
• Angiotensin receptor blockers (ARBs) 1, 3
• Calcium channel blockers 1, 3

Medications to Avoid as First-Line

• Beta-blockers are not recommended for uncomplicated hypertension due to inferior efficacy, being 36% less effective than calcium channel blockers and 30% less effective than thiazides for stroke prevention 1
• Alpha-blockers are not used as first-line therapy due to inferior cardiovascular disease prevention compared to thiazides 1
• Based on ALLHAT data, doxazosin is no longer an acceptable initial pharmacological agent 6

Common Pitfalls and Monitoring

• Maintain potassium levels >3.5 mmol/L when using thiazide diuretics to avoid increased ventricular ectopy 1
• Monitor serum creatinine, eGFR, and potassium within 7-14 days after initiating ACE inhibitors, ARBs, or diuretics, then at least annually 1
• Avoid combining ACE inhibitors and ARBs due to lack of added benefit and increased adverse events 1
• In elderly hypertensive patients, lower blood pressure gradually to avoid complications 5
• Refer patients not achieving target blood pressure on three drugs (including a diuretic) to a specialist 5

Target Blood Pressure Goals

• For adults <65 years: <130/80 mmHg 3
• For adults ≥65 years: SBP <130 mmHg 3
• For diabetic patients: <130/80 mmHg 5