What is the next step in managing a patient with elevated diastolic blood pressure who is already on perindopril (Angiotensin-Converting Enzyme Inhibitor) 8mg?

Management of Elevated Diastolic Blood Pressure on Perindopril 8mg

Add a calcium channel blocker (amlodipine 5mg daily) or a thiazide-like diuretic (indapamide 2.5mg daily) to your current perindopril 8mg regimen to achieve blood pressure control. 1

Rationale for Combination Therapy

You are already on the maximum recommended dose of perindopril (8mg daily) for hypertension 2, so dose escalation is not an option. The 2024 ESC Guidelines explicitly recommend that when blood pressure is not controlled with a two-drug combination (or in your case, monotherapy at maximum dose), escalation to a three-drug combination is the next step, typically consisting of a RAS blocker (your perindopril) with a dihydropyridine calcium channel blocker AND a thiazide/thiazide-like diuretic 1.

Specific Next Steps

First-Line Addition Options:

• Add amlodipine 5-10mg once daily - This creates the preferred ACE inhibitor + calcium channel blocker combination that has demonstrated superior blood pressure control and cardiovascular outcomes 1

• Add indapamide 2.5mg once daily - This creates the ACE inhibitor + thiazide-like diuretic combination, which was proven effective in the PROGRESS trial (perindopril + indapamide reduced stroke by 43%) 1

If Two-Drug Combination Fails:

Progress to triple therapy by adding the third agent you didn't initially select (so perindopril + amlodipine + indapamide), preferably as a single-pill combination if available 1. This three-drug regimen is the standard approach before considering resistant hypertension 1.

Target Blood Pressure

Your treatment target should be systolic 120-129 mmHg, provided this is well tolerated 1. The diastolic target should remain below 80-90 mmHg depending on your specific cardiovascular risk profile 1.

Resistant Hypertension Protocol

If blood pressure remains uncontrolled on the three-drug combination (perindopril + calcium channel blocker + thiazide-like diuretic), you meet criteria for resistant hypertension. At that point 1:

• Reinforce lifestyle modifications, especially sodium restriction to <2g/day
• Add low-dose spironolactone 25mg daily (if potassium <4.5 mmol/L and eGFR >30 mL/min) - this is the most effective fourth-line agent 1
• If spironolactone is not tolerated, consider eplerenone, amiloride, bisoprolol, or doxazosin 1
• Refer to a hypertension specialist if uncontrolled on ≥3 drugs 1

Important Caveats

Do not combine perindopril with an ARB (like losartan or telmisartan) - dual RAS blockade is explicitly not recommended due to increased risk of hyperkalemia, hypotension, and renal dysfunction without additional benefit 1.

Monitor renal function and potassium when adding diuretics or additional agents, especially if considering spironolactone later 1. Check these labs within 1-2 weeks of any medication change.

Ensure medication adherence - single-pill combination formulations significantly improve compliance and should be prioritized when available 1.

Confirm true hypertension with home blood pressure monitoring or 24-hour ambulatory monitoring if there's suspicion of white-coat hypertension, particularly if there's a >20/10 mmHg difference between clinic and home readings 1.