What are the next steps if blood pressure remains uncontrolled on lisinopril (angiotensin-converting enzyme inhibitor) 10 mg?

Management of Uncontrolled Blood Pressure on Lisinopril 10 mg

If blood pressure remains uncontrolled on lisinopril 10 mg, the next step is to increase the dose to 20-40 mg daily as recommended by the FDA labeling, with further dose titration up to a maximum of 80 mg daily if needed. 1

Dose Optimization of Lisinopril

When blood pressure is not adequately controlled on the initial 10 mg dose of lisinopril, the following approach is recommended:

1. Increase lisinopril dose:

   • Titrate up to 20 mg daily as the first step
   • Further increase to 40 mg daily if needed
   • Maximum FDA-approved dose is 80 mg daily 1
   • Allow 2-4 weeks between dose adjustments to assess full response 2

2. Monitoring during dose titration:

   • Monitor blood pressure response
   • Check renal function and electrolytes, particularly in elderly patients or those with renal impairment
   • Target blood pressure should be <130/80 mmHg 2

Adding a Second Agent (Step 2 Treatment)

If blood pressure remains uncontrolled despite optimal lisinopril dosing:

• Add a calcium channel blocker (CCB) as the preferred second agent 3, 2
• For patients who cannot tolerate a CCB (due to edema or other side effects), add a thiazide-like diuretic 3
• For Black patients of African or Caribbean origin, consider an ARB instead of continuing the ACE inhibitor, in combination with a CCB 3

Step 3 Treatment

If blood pressure remains uncontrolled on dual therapy:

• Ensure optimal dosing of both medications before adding a third agent 3
• Add a thiazide-like diuretic if not already part of the regimen 3, 2
• The optimal three-drug combination is ACE inhibitor (or ARB) + CCB + thiazide-like diuretic 3

Step 4 Treatment (Resistant Hypertension)

If blood pressure remains >140/90 mmHg despite optimal triple therapy:

• Add spironolactone 25 mg daily as the preferred fourth agent if serum potassium is <4.6 mmol/L and eGFR >45 ml/min/1.73m² 3
• If spironolactone is contraindicated or not tolerated, consider:
  • Alpha-blocker (e.g., doxazosin)
  • Beta-blocker
  • Eplerenone
  • Clonidine 3

Important Considerations

• Medication adherence: Ensure the patient is taking medications as prescribed, as non-adherence is a common cause of apparent treatment failure 3
• White coat effect: Consider ambulatory or home blood pressure monitoring to confirm true uncontrolled hypertension 3
• Secondary causes: Consider screening for secondary hypertension if blood pressure remains difficult to control despite multiple medications 3
• Lifestyle modifications: Reinforce importance of sodium restriction, weight loss, physical activity, and alcohol moderation 2
• Drug interactions: Review all medications for potential interactions that may reduce efficacy of antihypertensive therapy 3

Special Populations

• Elderly patients: May respond better to calcium channel blockers or diuretics as initial therapy, but dose titration of lisinopril is still appropriate if already initiated 3
• Patients with renal impairment: Reduce initial dose if creatinine clearance ≤30 ml/min, but dose can still be titrated based on response 1

By following this stepwise approach, most patients with hypertension can achieve target blood pressure control, reducing their risk of cardiovascular events, stroke, and mortality.