What is the role of Cardizem (Diltiazem) in treating hypertension?

Cardizem (Diltiazem) for Hypertension

Diltiazem is an effective antihypertensive agent that can be used as monotherapy or add-on therapy for hypertension, but it should NOT be used in patients with heart failure with reduced ejection fraction (HFrEF) or left ventricular systolic dysfunction. 1

Role and Positioning in Hypertension Treatment

General Hypertension (Uncomplicated)

• Diltiazem is acceptable as first-line therapy for general hypertension prevention when the blood pressure target is <140/90 mm Hg, though ACE inhibitors, ARBs, thiazides, or dihydropyridine calcium channel blockers are more commonly preferred. 1
• For patients with high cardiovascular risk (diabetes, chronic kidney disease, known CAD, or 10-year Framingham risk ≥10%), diltiazem can be used but the blood pressure target is lower at <130/80 mm Hg. 1

Specific Clinical Scenarios Where Diltiazem Has Value

Stable Angina with Hypertension:

• Diltiazem can substitute for beta-blockers when beta-blockers are contraindicated or cause intolerable side effects in patients with stable angina, BUT only if the patient does NOT have bradycardia or left ventricular dysfunction. 1
• Target blood pressure is <130/80 mm Hg. 1
• Diltiazem reduces myocardial oxygen demand by decreasing peripheral vascular resistance and lowering blood pressure, while increasing myocardial oxygen supply through coronary vasodilation. 1

Diabetes with Hypertension:

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) may reduce coronary events and have been shown in short-term studies to reduce albumin excretion. 1
• However, ACE inhibitors or ARBs are generally preferred as first-line agents in diabetic patients. 1

Mechanism and Efficacy

How Diltiazem Works:

• Inhibits calcium influx during membrane depolarization of cardiac and vascular smooth muscle. 2
• Decreases sinoatrial and atrioventricular conduction, slows heart rate, and has negative inotropic effects. 1
• Produces dose-dependent decreases in systemic blood pressure and peripheral resistance. 2

Clinical Trial Evidence:

• The NORDIL study (10,881 patients) demonstrated that diltiazem was as effective as diuretics and beta-blockers in preventing the combined endpoint of stroke, myocardial infarction, and cardiovascular death (relative risk 1.00,95% CI 0.87-1.15). 3
• Diltiazem showed a 20% reduction in fatal and non-fatal stroke compared to diuretics/beta-blockers (relative risk 0.80,95% CI 0.65-0.99, p=0.04). 3
• Monotherapy studies show diltiazem 360 mg/day effectively reduces blood pressure from baseline 156/100 mm Hg to 145/90 mm Hg. 4

Absolute Contraindications

DO NOT USE diltiazem in:

• Heart failure with reduced ejection fraction (HFrEF) or left ventricular systolic dysfunction - nondihydropyridine calcium channel blockers have myocardial depressant activity and clinical trials show no benefit or worse outcomes. 1
• Significant sinus or atrioventricular node dysfunction. 1
• Decompensated heart failure. 1
• Severe bradycardia. 1

Dosing and Administration

Practical Dosing:

• Extended-release formulation allows once-daily dosing. 5
• Effective dose range: 240-480 mg/day for most patients (85% require 360 mg/day). 5, 4
• Doses ≥240 mg/day provide trough drug levels within therapeutic range (≥40 ng/mL). 5
• Blood pressure reduction is clearly dose-related. 5

Drug Interactions and Cautions

Beta-Blocker Combination:

• Use caution when combining diltiazem with beta-blockers - risk of excessive bradycardia or heart block. 1
• If combination therapy is needed with beta-blockers, prefer long-acting dihydropyridine calcium channel blockers (like amlodipine) over diltiazem. 1

Adverse Effects

Safety Profile:

• Generally well-tolerated with adverse events similar to placebo in controlled trials. 5, 4
• Side effects are mild when they occur. 5, 4
• Discontinuation rates due to adverse effects are low (1 in 40 patients in one study). 4
• More effective in older patients without increased orthostatic hypotension. 4

Clinical Bottom Line

Use diltiazem for hypertension when:

• Patient has stable angina and cannot tolerate beta-blockers (without bradycardia or LV dysfunction). 1
• Patient needs alternative to or addition to first-line agents (ACE inhibitors, ARBs, thiazides). 1
• Patient is older and may benefit from stroke reduction. 3, 4

Avoid diltiazem when:

• Any degree of heart failure with reduced ejection fraction exists. 1
• Significant conduction system disease is present. 1
• Patient is already on beta-blocker therapy (consider dihydropyridine CCB instead). 1