What antihypertensive medication options are appropriate for a hypertensive patient on lisinopril who develops gingival bleeding while taking amlodipine?

Antihypertensive Management for Amlodipine-Induced Gingival Bleeding

Discontinue amlodipine immediately and add a thiazide or thiazide-like diuretic (chlorthalidone or indapamide) to the existing lisinopril regimen, as this combination represents guideline-recommended first-line therapy and will resolve the gingival bleeding while maintaining blood pressure control. 1

Immediate Action: Discontinue Amlodipine

• Amlodipine-induced gingival bleeding is a well-documented adverse effect that occurs in approximately 10% of patients on calcium channel blockers, with cases reported even at doses as low as 5 mg daily. 2, 3, 4
• The gingival enlargement and bleeding typically resolve after drug cessation, though surgical intervention may be needed in severe cases. 5
• Cases have been reported developing as rapidly as 2 months after initiation, making this a time-sensitive clinical concern. 6

Preferred Replacement Strategy

Add a Thiazide/Thiazide-Like Diuretic

The 2024 ESC Guidelines explicitly recommend combining a RAS blocker (your patient's lisinopril) with either a dihydropyridine CCB or a diuretic as preferred first-line combination therapy. 1 Since the CCB option has failed due to adverse effects, the logical next step is:

• Chlorthalidone 12.5-25 mg daily is the preferred agent based on its prolonged half-life and proven cardiovascular disease reduction. 7
• Indapamide is an equally acceptable thiazide-like alternative with strong evidence for cardiovascular event reduction. 1
• This ACE inhibitor + diuretic combination has demonstrated effective BP reduction and CVD event prevention in major trials. 1

Alternative: Switch to a Different Calcium Channel Blocker Class

If you absolutely need a third drug class rather than intensifying with a diuretic:

• Non-dihydropyridine CCBs (diltiazem or verapamil) have significantly lower rates of gingival hyperplasia compared to dihydropyridines like amlodipine. 5
• However, avoid non-dihydropyridines if the patient has heart failure with reduced ejection fraction, as they can worsen left ventricular dysfunction. 8, 9
• This is a less preferred option compared to adding a diuretic, as the 2024 ESC Guidelines prioritize ACE inhibitor + diuretic combinations. 1

Three-Drug Combination if Needed

If blood pressure remains uncontrolled on lisinopril plus diuretic, escalate to a three-drug combination using a RAS blocker + diuretic + a different CCB (preferably a non-dihydropyridine if no contraindications exist), ideally as a single-pill combination. 1

Critical Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB) - this is explicitly not recommended due to increased adverse events without additional benefit. 1
• Do not simply reduce the amlodipine dose - gingival hyperplasia can occur even at 5 mg daily, and dose reduction is unreliable for resolution. 3, 6
• Avoid beta-blockers as routine add-on therapy unless there are compelling indications such as angina, post-MI, heart failure with reduced ejection fraction, or need for heart rate control. 1
• Monitor renal function and electrolytes when adding a diuretic to an ACE inhibitor, particularly potassium and creatinine levels. 7

Blood Pressure Targets

• Target systolic BP of 120-129 mmHg in most adults, provided treatment is well tolerated. 1
• If this target cannot be achieved due to tolerability issues, apply the "as low as reasonably achievable" (ALARA) principle. 1
• The combination of ACE inhibitor + thiazide diuretic should provide sufficient BP reduction for most patients. 1

Monitoring After Drug Switch

• Gingival bleeding should improve within weeks of amlodipine discontinuation, though complete resolution of hyperplastic tissue may take longer or require dental intervention. 4, 5
• Reassess BP control 2-4 weeks after adding the diuretic to ensure adequate response.
• Check serum creatinine, potassium, and sodium within 2-4 weeks of initiating diuretic therapy, especially in patients on ACE inhibitors. 7