What is the best medication to take with diltiazem (Calcium Channel Blocker) for Hypertension (Htn)?

From the Guidelines

The best medication to take with diltiazem for hypertension is typically an ACE inhibitor like lisinopril (10-40mg daily) or an ARB like losartan (25-100mg daily), as these combinations have demonstrated effective reduction of blood pressure and cardiovascular disease events 1. When considering combination therapy with diltiazem, it's essential to choose medications that target different blood pressure mechanisms to achieve better control.

• Diltiazem blocks calcium channels to relax blood vessels,
• while ACE inhibitors or ARBs work by inhibiting the renin-angiotensin system to reduce blood pressure. However, beta-blockers should generally be avoided with diltiazem as the combination can excessively slow heart rate, increasing the risk of bradycardia and heart block 1. Given the most recent guidelines, combining a RAS blocker (either an ACE inhibitor or an ARB) with a dihydropyridine CCB or diuretic is recommended for most patients with confirmed hypertension as initial therapy 1. When starting combination therapy, begin with lower doses of both medications and monitor for side effects like dizziness, swelling, or electrolyte imbalances. Blood pressure should be checked regularly, and kidney function tests are recommended periodically, especially when using ACE inhibitors or ARBs with diltiazem. It's also important to consider fixed-dose single-pill combination treatment to improve adherence and simplify the treatment regimen 1.

From the FDA Drug Label

Cimetidine: A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1-week course of cimetidine at 1200 mg per day and a single dose of diltiazem 60 mg. Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Digitalis: Administration of diltiazem hydrochloride with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Ivabradine: Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Quinidine: Diltiazem significantly increases the AUC(0 → ∞) of quinidine by 51%, T1/2 by 36%, and decreases its CLoral by 33% Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins.

The best medication to take with diltiazem for hypertension is not explicitly stated in the provided drug label. However, based on the information provided, caution is advised when taking diltiazem with other medications.

• Cimetidine and quinidine may increase diltiazem plasma levels.
• Clonidine may cause sinus bradycardia.
• Digitalis may increase plasma digoxin concentrations.
• Ivabradine should be avoided due to increased exposure and risk of bradycardia.
• Statins may have increased AUC when taken with diltiazem, and dose adjustments may be necessary. It is essential to carefully monitor patients for changes in pharmacological effects when initiating or discontinuing therapy with these medications. 2

From the Research

Medication Options for Hypertension with Diltiazem

• Diltiazem can be combined with hydrochlorothiazide, a thiazide diuretic, to enhance its antihypertensive effect, as shown in a study published in 1993 3.
• The combination of diltiazem and hydrochlorothiazide was found to lower both supine diastolic blood pressure and systolic blood pressure significantly more than either single agent alone 3.
• Another study published in 2020 recommends the use of thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) in combination therapy for hypertension, but notes that ACEIs and ARBs should not be used simultaneously 4.
• A 2019 study found that combinations of lisinopril, losartan, or valsartan with hydrochlorothiazide, alone or with amlodipine, were equally effective in reducing blood pressure and improving arterial stiffness in patients with essential hypertension 5.
• A 1988 study compared the efficacy of sustained-release diltiazem with captopril, alone and in combination, in patients with mild to moderate essential hypertension, and found that both drugs lowered blood pressure significantly, with diltiazem having a greater effect on diastolic blood pressure 6.
• A 2022 review of hypertension treatment recommends first-line therapy with lifestyle modification, and first-line drug therapy with a thiazide or thiazide-like diuretic, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and a calcium channel blocker, titrated to achieve a target blood pressure of less than 130/80 mm Hg 7.

Combination Therapy Considerations

• The choice of combination therapy should be based on the individual patient's needs and medical history, as well as the presence of any comorbidities or contraindications 4, 7.
• Combination therapy can be used to achieve better blood pressure control, reduce the risk of cardiovascular disease, and improve patient outcomes 3, 5, 6, 7.