What is the best medication to lower elevated diastolic blood pressure in a patient with hypertension?

Best Medication to Lower Diastolic Blood Pressure

For lowering elevated diastolic blood pressure, thiazide or thiazide-like diuretics (such as chlorthalidone or hydrochlorothiazide) are the most effective first-line agents, with ACE inhibitors, ARBs, and calcium channel blockers serving as equally effective alternatives depending on patient characteristics. 1

First-Line Medication Classes

The 2024 ESC guidelines establish that four drug classes have demonstrated the most effective reduction of both blood pressure and cardiovascular events: ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (CCBs), and thiazides/thiazide-like diuretics 1. These are all recommended as first-line treatments with equivalent efficacy for diastolic blood pressure reduction 1.

Thiazide Diuretics: The Historical Gold Standard

• Thiazide-type diuretics have been the basis of antihypertensive therapy in the majority of placebo-controlled outcome trials where cardiovascular events, including strokes, coronary heart disease, and heart failure, have been reduced by blood pressure lowering 1.
• In the landmark ALLHAT trial, 60% of patients whose blood pressure was controlled to 140/90 mmHg received two or more agents, demonstrating that most patients require combination therapy 1.
• Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and proven cardiovascular disease reduction in trials 2.

ACE Inhibitors and ARBs: Equally Effective Alternatives

• ACE inhibitors and ARBs demonstrate broadly similar cardiovascular protection and blood pressure lowering compared to thiazide diuretics 1.
• Lisinopril demonstrated superior reductions of systolic and diastolic blood pressure compared to hydrochlorothiazide in a population that was 75% Caucasian 3.
• Studies have shown equivalence of benefit between ACE inhibitors and ARBs (candesartan or valsartan) in heart failure, with both classes effective in lowering blood pressure 1.

Calcium Channel Blockers: Particularly Effective for Diastolic Reduction

• Amlodipine produces clinically significant reductions in blood pressure with mean reductions of 23/13 mmHg (supine) and 24/12 mmHg (upright), demonstrating particularly strong diastolic effects 4.
• The magnitude of blood pressure reduction with amlodipine correlates with pretreatment elevation; individuals with moderate hypertension (diastolic pressure 105-114 mmHg) had about 50% greater response than patients with mild hypertension (diastolic pressure 90-104 mmHg) 5.
• Amlodipine demonstrated superior antihypertensive efficacy compared to verapamil and comparable efficacy with atenolol, hydrochlorothiazide, and captopril 6.
• In a direct comparison, amlodipine produced significantly greater reductions in mean diastolic blood pressure compared to losartan (-12.6 vs -10.3 mmHg; p=0.002) 7.

Combination Therapy for Optimal Diastolic Control

Given trial evidence for more effective blood pressure control versus monotherapy, combination blood pressure-lowering treatment is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy 1.

Preferred Combinations

• The preferred initial combinations are a RAS blocker (either an ACE inhibitor or ARB) with a dihydropyridine CCB or diuretic 1.
• The combination of 2.5 mg amlodipine with 5 mg lisinopril produced significantly more blood pressure lowering in a higher percentage of patients than individual low doses of either agent 8.
• When blood pressure is not controlled with a two-drug combination, increasing to a three-drug combination is recommended, usually a RAS blocker with a dihydropyridine CCB and a thiazide/thiazide-like diuretic, preferably in a single-pill combination 1.

Additive Effects

• When used in combination with ACE inhibitors, beta-blockers, or thiazide diuretics, amlodipine produces important additional antihypertensive effects 6.
• The combination of amlodipine with an ACE inhibitor has demonstrated superior blood pressure control compared to either agent alone in patients with diabetes, chronic kidney disease, or heart failure 2.

Race-Based Considerations

• For Black patients with hypertension, a dihydropyridine calcium channel blocker like amlodipine is preferred as initial therapy over ACE inhibitors or ARBs 2.
• Lisinopril was less effective in reducing blood pressure in Black patients than in Caucasian patients 3.
• The combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB in Black patients 2.
• In a comparative study, the response rate was significantly greater after treatment with amlodipine than with losartan in African Americans (62.5% vs 41.4%; p=0.033) 7.

Special Populations and Comorbidities

Heart Failure Patients

• Patients with heart failure and hypertension should be treated with diuretics, ACE inhibitors (or ARBs), β-blockers, and aldosterone receptor antagonists 1.
• Thiazide diuretics should be used for blood pressure control and to reverse volume overload; in severe heart failure or severe renal impairment, loop diuretics should be used for volume control 1.
• Drugs to avoid in patients with heart failure and hypertension are nondihydropyridine CCBs (such as verapamil and diltiazem), clonidine, and moxonidine 1.

Patients with Coronary Artery Disease

• In patients with elevated diastolic blood pressure who have coronary artery disease and heart failure with evidence of myocardial ischemia, blood pressure should be lowered slowly, with caution advised in inducing falls of diastolic blood pressure below 60 mmHg if the patient has diabetes mellitus or is over age 60 years 1.

Elderly Patients

• Elderly patients have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40-60%, and a lower initial dose may be required 5.
• In older hypertensive individuals with wide pulse pressures, lowering systolic blood pressure may cause very low diastolic blood pressure values (<60 mmHg), which should alert the clinician to assess carefully for untoward signs or symptoms 1.

Critical Pitfalls to Avoid

• Do not combine two RAS blockers (ACE inhibitor and ARB), as this increases adverse events without additional benefit 1, 2.
• Beta-blockers should not be used as first-line monotherapy for uncomplicated hypertension; they are recommended to be combined with other major blood pressure-lowering drug classes when there are compelling indications such as angina, post-myocardial infarction, heart failure with reduced ejection fraction, or for heart rate control 1.
• Alpha-adrenergic blockers such as doxazosin should be used only if other drugs for hypertension management are inadequate at maximum tolerated doses, as the ALLHAT trial showed a 2.04-fold increase in relative risk of developing heart failure compared with chlorthalidone treatment 1.
• Short-acting calcium channel blockers are not recommended based on safety data 1.

Monitoring and Target Goals

• Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg for higher-risk patients 1, 2.
• Blood pressure should be reassessed within 2-4 weeks after any medication adjustment, with the goal of achieving target blood pressure within 3 months of initiating or modifying therapy 2.
• With amlodipine, steady-state plasma levels are reached after 7-8 days of consecutive daily dosing, and antihypertensive effectiveness is maintained for at least 24 hours with chronic once-daily oral administration 5.