From the Guidelines
Combining a non-dihydropyridine (non-DHP) calcium channel blocker (CCB) with a dihydropyridine (DHP) CCB is a recommended approach for hypertension treatment in certain patients, as supported by the 2024 ESC guidelines 1. This combination typically includes a non-DHP CCB such as verapamil (120-360 mg daily) or diltiazem (120-540 mg daily) with a DHP CCB like amlodipine (5-10 mg daily), nifedipine (30-90 mg daily), or felodipine (5-10 mg daily). The key benefits of this combination include:
- Complementary mechanisms of action, with DHP CCBs causing peripheral vasodilation and non-DHP CCBs affecting cardiac conduction and heart rate
- Potential for improved blood pressure control, particularly in patients with resistant hypertension or comorbid conditions like angina or atrial fibrillation
- Reduced risk of adverse effects, as lower doses of each individual agent may be used in combination therapy 1
However, caution is needed when using this combination, as it may cause:
- Excessive bradycardia, heart block, or hypotension, especially in elderly patients or those with cardiac conduction disorders
- Increased risk of adverse effects, such as edema, dizziness, or headache Regular monitoring of heart rate, blood pressure, and ECG is recommended, particularly when initiating therapy or adjusting doses. This combination should be avoided in patients with:
- Severe heart failure or significant conduction abnormalities
- Other conditions that may be exacerbated by the combination, such as renal impairment or hepatic dysfunction
In general, the 2024 ESC guidelines recommend upfront combination therapy, including single-pill combinations, for adults with confirmed hypertension 1. The major four drug classes, including ACE inhibitors, ARBs, dihydropyridine CCBs, and thiazide or thiazide-like diuretics, are recommended as first-line BP-lowering medications, either alone or in combination. However, the combination of two RAS blockers is not recommended, and other combinations, such as non-DHP and DHP CCBs, should be used with caution and careful monitoring.
From the Research
Non-DHP and DHP CCB Combination for HTN Treatment
- The combination of non-dihydropyridine (Non-DHP) and dihydropyridine (DHP) calcium channel blockers (CCBs) has been proposed for the treatment of hypertension 2.
- This combination has been shown to produce a significantly greater reduction in systolic and diastolic blood pressures compared to monotherapy with either DHP or Non-DHP CCBs 2.
- The efficacy of dual CCB therapy has been demonstrated in a meta-analysis of six studies, which found that it lowered blood pressure significantly better than CCB monotherapy without increasing adverse events 2.
- However, the use of dual CCB therapy should be done with caution, as there is a lack of long-term outcome data on its efficacy and safety 2.
Comparison with Other Combination Therapies
- Combination therapy with a CCB and an angiotensin-converting enzyme (ACE) inhibitor has been shown to be effective in reducing blood pressure and major clinical events compared to an ACE inhibitor-diuretic combination 3.
- The combination of an ACE inhibitor and a CCB has also been found to have superior blood-pressure-lowering efficacy and safety compared to either group used as monotherapy 3.
- However, the combination of an ACE inhibitor and an angiotensin II-receptor blocker has not been found to be superior to either group as monotherapy in patients with hypertension 3.
Patient-Specific Considerations
- Calcium channel blockers, including Non-DHP and DHP CCBs, may have a special role in the therapy of certain patient groups, such as the elderly, black patients, or those with early end-organ damage 4.
- Non-DHP CCBs, such as verapamil and diltiazem, may be used in patients with supraventricular tachycardias, including acute and chronic atrial fibrillation 4.
- DHP CCBs, such as nifedipine, may be used in patients with severe hypertension, Raynaud's phenomenon, or peripheral vascular disease 4.