What antihypertensive should I try next in a patient with uncontrolled hypertension (high blood pressure) on amlodipine (calcium channel blocker)?

Next Antihypertensive After Amlodipine Failure

For a patient with uncontrolled hypertension on amlodipine, add a renin-angiotensin system (RAS) blocker such as an ACE inhibitor or ARB as the next antihypertensive agent. 1

Treatment Algorithm for Amlodipine Non-Responders

Step 1: Add a RAS Blocker

• Add an ACE inhibitor (e.g., perindopril 2 mg daily) OR
• Add an ARB (e.g., losartan 50 mg daily) 1

This combination provides synergistic blood pressure lowering effects through complementary mechanisms:

• Amlodipine blocks calcium channels in vascular smooth muscle
• RAS blockers prevent angiotensin II-mediated vasoconstriction and aldosterone release

Step 2: If BP Still Uncontrolled

Add a thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) 1, 2

Research shows that adding a thiazide diuretic to the combination of a calcium channel blocker and RAS blocker provides significantly better blood pressure reduction than adding a beta-blocker 2.

Step 3: For Resistant Hypertension

If BP remains uncontrolled on a three-drug regimen (CCB + RAS blocker + diuretic), add spironolactone (a mineralocorticoid receptor antagonist) 1

Special Considerations

Comorbidities That May Influence Choice

• Chronic Kidney Disease: Prioritize RAS blockers, especially with albuminuria 1
• Diabetes: ACE inhibitor or ARB preferred as second agent 1
• Heart Failure: Add ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist 1
• Coronary Artery Disease: Consider beta-blocker + RAS blocker combination 1
• Prior Stroke: RAS blockers, CCBs, and diuretics are first-line drugs 1

Monitoring Recommendations

• Check serum creatinine, eGFR, and potassium within 2-4 weeks after starting a RAS blocker 1
• Monitor for ankle edema (CCB side effect) and cough (ACE inhibitor side effect)
• Assess for orthostatic hypotension, especially in elderly patients

Common Pitfalls to Avoid

1. Inadequate dosing: Ensure amlodipine is at maximum dose (10mg) before adding another agent
2. Overlooking adherence issues: Verify patient is taking medication as prescribed
3. Not addressing lifestyle factors: Reinforce sodium restriction, weight loss, and physical activity
4. Inappropriate combinations: Avoid combining non-dihydropyridine CCBs (diltiazem, verapamil) with beta-blockers due to additive negative chronotropic effects
5. Not considering secondary hypertension: Consider screening for secondary causes if BP remains difficult to control despite multiple medications

The 2024 ESC guidelines strongly support this approach, recommending combination therapy with a CCB and RAS blocker as a cornerstone of hypertension management, with the addition of a diuretic as the third agent when needed 1.