What is the next step for a patient with elevated Blood Pressure (BP) on perindopril (Angiotensin-Converting Enzyme Inhibitor) indapamide (Thiazide-like Diuretic) 8mg/2.5mg?

Management of Elevated Blood Pressure on Perindopril/Indapamide 8mg/2.5mg

The next step for a patient with elevated blood pressure despite treatment with perindopril/indapamide 8mg/2.5mg should be the addition of a calcium channel blocker, preferably amlodipine, to create a three-drug combination therapy. 1, 2

Assessment of Current Therapy

• Perindopril/indapamide combination is an effective antihypertensive regimen combining an ACE inhibitor with a thiazide-like diuretic, but inadequate control indicates the need for treatment intensification 1
• The current dose of perindopril 8mg represents the maximum recommended dose for hypertension, while indapamide 2.5mg is also at its standard therapeutic dose 3, 1
• Persistence of elevated BP despite this combination suggests the need for adding a third agent rather than further dose escalation of current medications 1

Recommended Next Steps

First-line option:

• Add a dihydropyridine calcium channel blocker (CCB), preferably amlodipine 5-10mg daily 1, 2
• This creates the preferred three-drug combination of RAS blocker + diuretic + CCB, which is recommended by current guidelines 1
• Triple therapy with perindopril/indapamide/amlodipine has demonstrated superior blood pressure reduction compared to dual therapy in randomized controlled trials 2

Monitoring after medication addition:

• Reassess blood pressure within 2-4 weeks after adding the third agent 1
• Monitor for potential side effects including peripheral edema (from amlodipine) and electrolyte disturbances 2
• Check renal function and electrolytes 1-2 weeks after initiation, particularly if the patient has risk factors for renal impairment 4

Evidence Supporting This Approach

• The 2024 ESC guidelines strongly recommend a three-drug combination of RAS blocker + CCB + thiazide/thiazide-like diuretic when two-drug combinations fail to control blood pressure 1
• The FORTISSIMO study demonstrated that patients with uncontrolled hypertension on previous combinations benefited from optimized therapy with perindopril/indapamide, with 84% reaching target BP 5
• Triple therapy with perindopril/indapamide/amlodipine has shown superior efficacy compared to dual therapy, with control rates exceeding 80% after appropriate up-titration 2

Special Considerations

• Fixed-dose single-pill combinations are preferred whenever possible to improve adherence 1
• If the patient has comorbid conditions like diabetes or previous stroke, the addition of amlodipine to create a triple therapy is particularly beneficial for cardiovascular risk reduction 1, 6
• For patients with renal impairment (creatinine clearance <30 mL/min), dose adjustment may be necessary, as perindopril elimination is decreased in these patients 3

Common Pitfalls to Avoid

• Avoid combining two RAS blockers (such as adding an ARB to the current ACE inhibitor), as this is not recommended due to increased risk of adverse events without additional benefit 1
• Do not discontinue current therapy before adding the third agent, as this could lead to rebound hypertension 1
• Be cautious about orthostatic hypotension when intensifying therapy, particularly in elderly patients or those with volume depletion 1

Target Blood Pressure

• For most adults, target systolic BP should be 120-129 mmHg, provided the treatment is well tolerated 1
• If this target cannot be achieved due to side effects, aim for the lowest BP that is reasonably achievable without compromising safety 1

By following this evidence-based approach of adding a calcium channel blocker to the current perindopril/indapamide regimen, most patients with previously uncontrolled hypertension can achieve target blood pressure with good tolerability.