What is the first-line pharmacotherapy for newly diagnosed hypertension?

First-Line Pharmacotherapy for Newly Diagnosed Hypertension

For newly diagnosed hypertension, initiate treatment with any of the following four drug classes: thiazide or thiazide-like diuretics (chlorthalidone or hydrochlorothiazide), ACE inhibitors, angiotensin receptor blockers (ARBs), or long-acting dihydropyridine calcium channel blockers (CCBs). 1

Evidence-Based Drug Class Selection

The 2022 WHO guidelines provide strong evidence (high quality) that all four major drug classes are equally acceptable as first-line agents 1. However, specific clinical contexts should guide your choice:

Thiazide Diuretics: The Default First Choice

Thiazide-type diuretics, particularly chlorthalidone, have the strongest evidence base for preventing cardiovascular mortality and should be your default first-line agent for uncomplicated hypertension. 2, 3

• Chlorthalidone demonstrated superior outcomes compared to ACE inhibitors (lisinopril) in preventing stroke and superior to CCBs (amlodipine) in preventing heart failure in the landmark ALLHAT trial involving over 33,000 patients 3
• Only thiazide diuretics and ACE inhibitors have been proven to reduce all-cause mortality compared to placebo, preventing approximately 2-3 deaths per 100 patients treated over 4-5 years 2
• Long-acting agents like chlorthalidone and indapamide are preferred over hydrochlorothiazide due to better cardiovascular outcomes 4

Population-Specific First-Line Choices

For Black patients: Start with either a thiazide diuretic or CCB, as these are more effective than ACE inhibitors in this population 4, 5, 6

For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g): ACE inhibitors or ARBs are mandatory first-line therapy 4, 5

For patients with established coronary artery disease: ACE inhibitors or ARBs should be your initial choice 4, 5

For patients aged 55 or older: CCBs or diuretics are generally more effective 4

For patients younger than 55 and white: ACE inhibitors or ARBs may be more effective initially 4

Monotherapy vs. Combination Therapy Algorithm

Stage 1 Hypertension (130-139/80-89 mmHg):

• Start with single-agent therapy 4, 5
• Titrate to maximum dose over 4 weeks if target not achieved 6

Stage 2 Hypertension (≥140/90 mmHg):

• Initiate combination therapy with two drugs from different classes, preferably as a single-pill combination 1, 4, 5
• Combination therapy improves adherence and achieves blood pressure control more rapidly 1, 5

Severe Hypertension (≥160/100 mmHg):

• Mandatory to start with two-drug combination therapy 4, 5
• Choose from: thiazide/thiazide-like diuretics + ACE inhibitor/ARB + long-acting dihydropyridine CCB 1

Critical Pitfalls to Avoid

Never combine ACE inhibitors with ARBs — this dual RAS blockade increases adverse effects without additional benefit 4, 5

Avoid beta-blockers as first-line therapy unless specific indications exist (prior MI, active angina, heart failure with reduced ejection fraction) 4, 5

Do not use alpha-blockers as first-line due to inferior cardiovascular protection 4

Beware of thiazide-induced hyperglycemia and diabetes — however, this does not reduce their efficacy in preventing cardiovascular events 2

Target Blood Pressure Goals

• Standard target: <140/90 mmHg for all patients without comorbidities 1
• Intensive target: <130/80 mmHg for patients with known CVD (strong recommendation) 1
• Consider <130 mmHg systolic for high-risk patients with diabetes, chronic kidney disease, or high CVD risk 1

Follow-Up Schedule

• Monthly reassessment after initiation or medication changes until target BP achieved 1
• Every 3-5 months once blood pressure is controlled 1