Hypertension Management with Perindopril and Second Agent

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 3
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 3, 1
The British Hypertension Society recommends combining drugs with complementary mechanisms of action - specifically an ACE inhibitor with either a calcium channel blocker or a diuretic 2

A calcium channel blocker is the preferred second agent to add to perindopril based on the most recent European Society of Cardiology guidelines 1, 4
The American College of Cardiology and European Society of Cardiology recommend a calcium channel blocker, particularly amlodipine, as the preferred second agent to add to perindopril 1, 4

If a calcium channel blocker is not tolerated or contraindicated, a thiazide diuretic is an effective alternative second agent 3, 5
The European Society of Cardiology and American Heart Association suggest that perindopril combined with a thiazide diuretic has shown synergistic effects in blood pressure reduction 3

In black patients, initial combination therapy should include a calcium channel blocker with either a thiazide diuretic or a RAS blocker 1, 4
For patients with resistant hypertension, adding spironolactone as a fourth agent should be considered if blood pressure remains uncontrolled on a three-drug regimen 1, 6

Avoid combining two RAS blockers, as this increases adverse effects without additional benefit, according to the European Society of Cardiology 7
Be cautious when combining beta-blockers with diuretics in patients at high risk for diabetes, as recommended by the British Hypertension Society 2
Monitor for orthostatic hypotension when using multiple antihypertensive agents, especially in elderly patients, as advised by the British Journal of Cancer and European Society of Cardiology 6, 7