What anti-hypertensive should I consider as an adjunct to bisoprolol (beta-blocker) + ramipril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Calcium Channel Blocker is the Best Adjunct to Bisoprolol + Ramipril for Hypertension

A calcium channel blocker (CCB), particularly a dihydropyridine CCB like amlodipine, is the most appropriate third antihypertensive agent to add to the combination of bisoprolol and ramipril. 1

Rationale for Adding a CCB

• The 2024 ESC guidelines strongly recommend that when BP is not controlled with a two-drug combination, increasing to a three-drug combination of a RAS blocker (ACE inhibitor or ARB), a dihydropyridine CCB, and a thiazide/thiazide-like diuretic is recommended (Class I, Level B recommendation) 1

• You currently have:

  • Bisoprolol (beta-blocker)
  • Ramipril (ACE inhibitor/RAS blocker)

• Adding a dihydropyridine CCB would create a complementary combination targeting different mechanisms of blood pressure control:

  • ACE inhibitor (ramipril): blocks the renin-angiotensin system
  • Beta-blocker (bisoprolol): reduces cardiac output and inhibits renin release
  • CCB: causes arterial vasodilation through different pathways

Evidence Supporting This Combination

• The European Society of Cardiology (ESC) and European Society of Hypertension (ESH) guidelines identify the combination of a calcium antagonist and ACE inhibitor as effective and well-tolerated 1

• The combination of a beta-blocker and calcium antagonist (dihydropyridine) is also recognized as effective 1

• Studies have shown that combinations of drugs from different classes improve BP control and patient adherence 1

• Fixed-dose combinations of bisoprolol and amlodipine have been shown to be effective with complementary modes of action 2

Specific CCB Recommendations

• Amlodipine (5-10 mg once daily) would be the most appropriate choice:

  • Well-studied in combination with ACE inhibitors
  • Once-daily dosing improves adherence
  • Effective 24-hour blood pressure control

• Alternative dihydropyridine CCBs include:

  • Felodipine (2.5-10 mg once daily)
  • Nifedipine LA (30-90 mg once daily)

Important Considerations

• Monitoring: Check blood pressure within 2-4 weeks after adding the CCB 3

• Side effects: Dihydropyridine CCBs may cause dose-related pedal edema, more common in women 1

• Avoid non-dihydropyridine CCBs: Diltiazem and verapamil should be avoided with beta-blockers due to increased risk of bradycardia and heart block 1

• Fixed-dose combinations: Consider a fixed-dose combination to improve adherence if available 1

Alternative Options if CCBs Are Not Tolerated

If a CCB is not tolerated, the next best option would be:

1. Thiazide/thiazide-like diuretic (e.g., hydrochlorothiazide 12.5-25 mg, chlorthalidone 12.5-25 mg, or indapamide 1.25-2.5 mg)

   • Monitor for electrolyte disturbances
   • Be aware that the combination of a thiazide and beta-blocker may increase the risk of new-onset diabetes 1

2. If triple therapy fails: Consider adding spironolactone (25-50 mg) as a fourth agent 1

Conclusion

For a patient already on bisoprolol and ramipril, adding a dihydropyridine calcium channel blocker like amlodipine represents the most evidence-based approach to optimize blood pressure control while minimizing adverse effects.