Classes of Antihypertensive Drugs
The five major classes of antihypertensive drugs proven to reduce cardiovascular events are: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, dihydropyridine calcium channel blockers, and beta-blockers. 1
Primary Drug Classes with Cardiovascular Outcome Evidence
First-Line Agents
ACE Inhibitors (e.g., lisinopril, ramipril, captopril) block the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion 1, 2
Angiotensin Receptor Blockers (ARBs) (e.g., losartan, valsartan) directly block angiotensin II receptors, providing similar benefits to ACE inhibitors with potentially fewer side effects like cough 1, 2
Thiazide-like Diuretics (e.g., chlorthalidone, indapamide) and thiazide diuretics (e.g., hydrochlorothiazide) reduce blood volume and have direct vascular effects; chlorthalidone has the strongest evidence base from large trials 1, 3, 4
Dihydropyridine Calcium Channel Blockers (e.g., amlodipine, nifedipine) block L-type calcium channels in vascular smooth muscle, causing vasodilation 1, 2
Beta-Blockers
- Beta-Blockers (e.g., metoprolol, atenolol, carvedilol) reduce heart rate and cardiac output by blocking beta-adrenergic receptors 1, 2
- These are indicated specifically for patients with prior myocardial infarction, active angina, or heart failure with reduced ejection fraction, but have not shown mortality reduction as blood pressure-lowering agents alone in the absence of these conditions 1
- Beta-blockers are less effective than other first-line agents for stroke prevention, particularly in older adults 1
Additional Drug Classes
Mineralocorticoid Receptor Antagonists
- Aldosterone Antagonists (e.g., spironolactone) are recommended for resistant hypertension when blood pressure remains ≥140/90 mmHg despite three other antihypertensive medications including a diuretic 1, 3
Alpha-Blockers
- Alpha-1 Adrenergic Blockers (e.g., doxazosin) are not recommended as first-line therapy because they are less effective for cardiovascular disease prevention than thiazide diuretics, showing increased risk of stroke and heart failure in head-to-head trials 1
Centrally Acting Agents
- Central Alpha-2 Agonists (e.g., clonidine, methyldopa) and Imidazoline Receptor Modulators reduce sympathetic outflow from the central nervous system 1, 2
- Methyldopa is specifically recommended for use in pregnancy 1, 3
Direct Vasodilators
- Direct-Acting Vasodilators (e.g., hydralazine) are typically reserved as third-step agents in resistant hypertension 1, 2
Non-Dihydropyridine Calcium Channel Blockers
- Non-Dihydropyridine Calcium Channel Blockers (e.g., verapamil, diltiazem) have rate-controlling properties and are useful for atrial fibrillation but are contraindicated in second- or third-degree AV block 1
Key Clinical Considerations
Important caveats when selecting drug classes:
- For patients with coronary artery disease, ACE inhibitors or ARBs are recommended as first-line therapy 1, 3
- For patients with albuminuria (UACR ≥30 mg/g), initial treatment should include an ACE inhibitor or ARB 1, 3
- For Black patients, thiazide diuretics or calcium channel blockers are preferred over ACE inhibitors as monotherapy due to reduced efficacy of ACE inhibitors in this population 1, 3
- ACE inhibitors and ARBs are absolutely contraindicated in pregnancy or women planning pregnancy 1, 3
- Thiazide diuretics can increase the risk of new-onset diabetes, particularly when combined with beta-blockers, requiring caution in high-risk patients 5
The evidence consistently demonstrates that blood pressure reduction itself, rather than a specific drug class, accounts for most cardiovascular benefit, though certain classes offer additional advantages in specific clinical scenarios. 1