Pharmacologic Treatment of Hypertension in Adults

First-Line Pharmacologic Agents

The World Health Organization provides a strong recommendation (high-quality evidence) for using any of the four drug classes (thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or long-acting dihydropyridine calcium channel blockers) as initial treatment for adults with hypertension requiring pharmacologic treatment 1, 2, 3
The American College of Cardiology recommends that diuretics, particularly chlorthalidone, may provide optimal first-step therapy based on meta-analyses and large RCTs 4

For patients with stage 1 hypertension (BP 130-139/80-89 mmHg), start with single-agent monotherapy and titrate dosage and sequentially add agents as needed to reach target 4
For patients with stage 2 hypertension (BP ≥140/90 mmHg or >20/10 mmHg above goal), initiate with two-drug combination therapy from different first-line classes, preferably using single-pill combination products 1, 2, 4

When blood pressure remains uncontrolled on initial therapy, add a second agent from a different first-line class, ensuring complementary mechanisms of action 1, 2
Most patients require multiple agents for adequate BP control, with a typical effective combination being a diuretic + ACE inhibitor or ARB + calcium channel blocker 1, 2, 4

For black adults without heart failure or CKD, initial treatment should include a thiazide diuretic or calcium channel blocker 4
For patients with diabetes, CKD, or proteinuria, prefer ACE inhibitor or ARB as initial agent 5

The target blood pressure is <140/90 mmHg for all patients without comorbidities 1, 2, 3
The target blood pressure is <130/80 mmHg for adults <65 years 6
The target systolic blood pressure is <130 mmHg for patients with known CVD (strong recommendation) 2, 6

Monthly follow-up is recommended after initiating or changing medications until target BP is achieved 2, 3, 6
Every 3-5 months, patients at goal should be monitored 2, 3, 6
Monitor renal function and potassium within the first 3 months for patients on ACE inhibitors, ARBs, or diuretics 6

Thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, and long-acting calcium channel blockers all have comparable and favorable side effect profiles as first-line agents, with ARBs demonstrating the lowest discontinuation rates due to adverse effects in head-to-head comparisons, according to the American Heart Association 7
The American Geriatrics Society recommends thiazide diuretics, such as chlorthalidone, as a first-line agent due to their superior cardiovascular outcomes 8
Calcium channel blockers are well-tolerated with predictable side effects related to vasodilation, as stated by the American Heart Association 7

Beta-blockers are significantly less effective than diuretics for stroke prevention and cardiovascular events, and should not be first-line unless ischemic heart disease or heart failure is present, according to the American Geriatrics Society 8
Alpha-blockers and central alpha-agonists are likely to produce more adverse effects, particularly in older adults, and are not recommended as first-line therapy, as stated by the American Geriatrics Society 8

The American Heart Association endorses all four first-line classes (thiazides, ACE inhibitors, ARBs, CCBs) equally, with strong recommendations based on cardiovascular outcome data 7