What is an appropriate second agent to add to Coversyl (perindopril) for hypertension management?

Adding a Second Agent to Perindopril for Hypertension Management

A calcium channel blocker (CCB) is the most appropriate second agent to add to Coversyl (perindopril) for hypertension management. 1

Rationale for Combination Therapy

• Most hypertensive patients require more than one drug to achieve blood pressure control, with combination therapy being necessary for the majority of patients 1
• When adding a second agent to an ACE inhibitor like perindopril, the most effective and complementary combinations include a calcium channel blocker or a thiazide diuretic 1
• The AB/CD algorithm from the British Hypertension Society recommends combining drugs with complementary mechanisms of action - specifically an ACE inhibitor (A) with either a calcium channel blocker (C) or a diuretic (D) 1

Preferred Second Agent: Calcium Channel Blocker

• A calcium channel blocker (particularly amlodipine) is the preferred second agent to add to perindopril based on the most recent European Society of Cardiology guidelines 1
• The combination of perindopril and amlodipine has demonstrated superior efficacy in reducing cardiovascular mortality and morbidity compared to other combinations 2
• This combination provides complementary mechanisms of action: perindopril blocks the renin-angiotensin system while calcium channel blockers work through vasodilation 2

Evidence Supporting Perindopril/CCB Combination

• The fixed combination of perindopril and amlodipine has shown significant blood pressure reductions of -41.9/-23.2 mmHg in clinical practice 3
• This combination achieves target blood pressure in approximately 66% of patients, including those previously uncontrolled on monotherapy 3
• The perindopril/amlodipine combination has demonstrated cardioprotective and renoprotective properties beyond blood pressure reduction 2

Alternative Second Agent: Thiazide Diuretic

• If a calcium channel blocker is not tolerated or contraindicated, a thiazide diuretic is an effective alternative second agent 1
• Perindopril combined with a thiazide diuretic has shown synergistic effects in blood pressure reduction 4
• The combination of an ACE inhibitor with a thiazide diuretic is particularly effective and well-tolerated 1

Dosing Considerations

• When adding a second agent to perindopril, start with low doses and titrate as needed 1
• For perindopril, the usual maintenance dose is 4-8 mg once daily, which can be increased to a maximum of 16 mg if needed 5
• Fixed-dose combinations can improve adherence and simplify the treatment regimen 1, 3

Special Populations and Considerations

• In black patients, initial combination therapy should include a calcium channel blocker with either a thiazide diuretic or a RAS blocker 1
• For elderly patients (>65 years), start with lower doses of perindopril (2-4 mg) and titrate cautiously 5
• In patients with resistant hypertension, adding spironolactone as a fourth agent should be considered if blood pressure remains uncontrolled on a three-drug regimen 1

Common Pitfalls to Avoid

• Avoid combining two RAS blockers (such as adding an ARB to perindopril), as this increases adverse effects without additional benefit 6
• Be cautious when combining beta-blockers with diuretics in patients at high risk for diabetes 1
• Monitor for orthostatic hypotension when using multiple antihypertensive agents, especially in elderly patients 1, 6