What is the difference between hydralazine and amlodipine for hypertension management?

Hydralazine vs Amlodipine for Hypertension Management

Amlodipine is superior to hydralazine for first-line management of hypertension due to its once-daily dosing, proven cardiovascular outcomes benefits, and better side effect profile. 1

Mechanism of Action and Classification

• Amlodipine is a dihydropyridine calcium channel blocker (CCB) that works by blocking calcium influx into vascular smooth muscle cells, causing vasodilation 1
• Hydralazine is a direct-acting vasodilator that works primarily on arterial smooth muscle through an unknown mechanism, with minimal effects on venous circulation 2

Efficacy in Blood Pressure Control

• Amlodipine provides smooth 24-hour blood pressure control with once-daily dosing (5-10mg), without orthostatic hypotension 3
• Hydralazine requires multiple daily doses (typically 3-4 times daily) for effective blood pressure control, making adherence more challenging 2
• Amlodipine demonstrates dose-dependent antihypertensive effects starting at 2.5mg with optimal effects at 5-10mg daily 1

Clinical Outcomes and Evidence Base

• Amlodipine has robust evidence from large randomized controlled trials (like ALLHAT) showing it is equally effective as thiazide diuretics in preventing coronary heart disease mortality and morbidity 4, 1
• Amlodipine-based therapy reduces the incidence of fatal and non-fatal strokes by 25% compared to atenolol-based therapy in diabetic patients 1
• Hydralazine lacks sufficient evidence from randomized controlled trials comparing it to placebo for mortality and morbidity outcomes in hypertension 2

Place in Treatment Guidelines

• Amlodipine is recommended as a first-line agent for hypertension by major guidelines including AHA/ACC and WHO 5
• Hydralazine is primarily recommended as a later-line option for resistant hypertension when first-line therapies fail 4
• In the 2024 ESC guidelines, hydralazine is positioned as a consideration only after spironolactone, eplerenone, beta-blockers, and alpha-blockers have been tried in resistant hypertension 4

Side Effect Profiles

• Amlodipine's most common side effect is peripheral edema (dose-dependent), but it generally has a favorable tolerability profile 1, 6
• Hydralazine has more significant adverse effects including:
  • Reflex tachycardia (requiring combination with beta-blockers) 2
  • Drug-induced lupus-like syndrome with long-term use 2
  • Hemolytic anemia, vasculitis, and glomerulonephritis in some cases 2

Special Populations

• Amlodipine is particularly effective in black patients for preventing heart failure and stroke compared to ACE inhibitors 5
• Amlodipine can be used in heart failure patients with persistent hypertension as a step 3 agent (unlike non-dihydropyridine CCBs like diltiazem and verapamil which are contraindicated in HFrEF) 4, 1
• Hydralazine has a specific role in acute hypertensive emergencies (administered intravenously) and in pregnancy-related hypertension 4

Combination Therapy

• Amlodipine works well in combination with ACE inhibitors, ARBs, beta-blockers, or thiazide diuretics, producing additional antihypertensive effects 7, 8
• Fixed-dose combinations with amlodipine (e.g., amlodipine/valsartan) are available and improve adherence 8
• Hydralazine is typically used in combination with beta-blockers to counteract reflex tachycardia 2

Cost and Accessibility

• Hydralazine is generally less expensive than amlodipine, which may be relevant in resource-limited settings 2
• Both medications are available as generic formulations, but amlodipine is more widely used globally 1, 2

In conclusion, amlodipine offers significant advantages over hydralazine for hypertension management including once-daily dosing, proven cardiovascular outcome benefits, better tolerability, and strong guideline recommendations as a first-line agent. Hydralazine should be reserved for specific situations such as resistant hypertension, acute hypertensive emergencies, or when cost is a major limiting factor.