What is the best medication for managing high diastolic blood pressure?

Best Medication for Diastolic Blood Pressure

For elevated diastolic blood pressure, ACE inhibitors (such as lisinopril), ARBs, dihydropyridine calcium channel blockers (such as amlodipine), and thiazide/thiazide-like diuretics are equally recommended as first-line agents, with combination therapy preferred for most patients with confirmed hypertension (BP ≥140/90 mmHg). 1, 2

First-Line Medication Classes

The following four drug classes have demonstrated the most effective reduction in both blood pressure and cardiovascular events for diastolic hypertension:

• ACE inhibitors (e.g., lisinopril, enalapril) effectively lower diastolic blood pressure and are particularly superior to hydrochlorothiazide in reducing both systolic and diastolic BP 1, 3
• ARBs (e.g., candesartan, losartan) provide similar benefits to ACE inhibitors but with fewer side effects like cough 1, 2
• Dihydropyridine calcium channel blockers (e.g., amlodipine) lower diastolic BP through arterial vasodilation 1, 2, 4
• Thiazide and thiazide-like diuretics (e.g., chlorthalidone, indapamide, hydrochlorothiazide) are particularly effective for diastolic hypertension 1

Treatment Algorithm

Initial Therapy Selection

For most patients with confirmed hypertension (BP ≥140/90 mmHg):

• Start with combination therapy using two drugs from different classes 1, 2
• Preferred combinations: RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker OR RAS blocker + thiazide/thiazide-like diuretic 1, 2
• Use single-pill combinations to improve adherence 1, 2

Exceptions requiring monotherapy initiation:

• Patients aged ≥85 years 1
• Symptomatic orthostatic hypotension 1
• Moderate-to-severe frailty 1, 2
• Elevated BP (systolic 120-139 mmHg or diastolic 70-89 mmHg) with concomitant indication for treatment 1

Dose Escalation Strategy

If BP not controlled with two-drug combination:

• Escalate to three-drug combination: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic 1, 2
• Preferably use single-pill combination 1

If BP not controlled with three-drug combination:

• Add spironolactone as fourth agent 1
• If spironolactone not effective or tolerated: consider eplerenone, beta-blocker (if not already indicated), centrally acting agent, alpha-blocker, hydralazine, or potassium-sparing diuretic 1

Blood Pressure Targets

• Primary target: <130/80 mmHg for most patients 1, 5
• Diastolic-specific target: <80 mmHg for all hypertensive patients 1, 2
• Minimum acceptable: <140/90 mmHg in all patients 1
• Achieve target within 3 months to ensure adherence and reduce cardiovascular risk 1

Special Considerations and Common Pitfalls

Beta-Blockers

• Not recommended as first-line for uncomplicated hypertension 1
• Reserve for compelling indications: angina, post-myocardial infarction, heart failure with reduced ejection fraction, or heart rate control 1

Critical Contraindications

• Never combine two RAS blockers (ACE inhibitor + ARB) - this increases adverse effects without additional benefit 1, 2

Race-Based Considerations

• In Black patients, thiazide diuretics and calcium channel blockers are more effective than beta-blockers and RAS inhibitors as monotherapy 1
• However, combination therapy remains preferred regardless of race 1

Monitoring Requirements

• Monitor for orthostatic hypotension, especially in older patients 2
• Monthly evaluation of adherence and therapeutic response until control achieved 1
• Consider home blood pressure monitoring to improve control 1

Metabolic Effects

• ACE inhibitors do not cause hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia 6
• Hydrochlorothiazide may increase plasma glucose and decrease serum potassium 7

Evidence Quality Note

The 2024 European Society of Cardiology guidelines 1 represent the most recent high-quality evidence, supported by the 2017 ACC/AHA guidelines 1. Both emphasize that blood pressure reduction itself—rather than the specific drug class—is primarily responsible for cardiovascular benefit, though the four first-line classes have the strongest evidence base for reducing morbidity and mortality 1, 5.