What blood pressure medications can be given with lisinopril (angiotensin-converting enzyme inhibitor)?

Blood Pressure Medications That Can Be Given With Lisinopril

Thiazide or thiazide-type diuretics (such as hydrochlorothiazide or chlorthalidone) are the most strongly recommended medications to combine with lisinopril for blood pressure control, based on extensive clinical trial evidence showing superior cardiovascular outcomes. 1

First-Line Combination Options

Thiazide/Thiazide-Type Diuretics (Preferred)

• Hydrochlorothiazide 12.5-25 mg once daily is the most common and well-studied combination with lisinopril 1
• Chlorthalidone 12.5-25 mg once daily may be preferred based on ALLHAT trial data showing superior stroke prevention compared to lisinopril monotherapy 1
• This combination is available as fixed-dose products (Prinzide, Zestoretic) in strengths of 10/12.5,20/12.5, or 20/25 mg 1
• The diuretic enhances the antihypertensive effect of lisinopril and lisinopril attenuates the hypokalemia induced by thiazides 2, 3

Calcium Channel Blockers

• Amlodipine 2.5-10 mg once daily is an effective second option when combined with lisinopril 1, 4
• The combination of amlodipine and lisinopril produces marked additional blood pressure reduction at both peak and trough levels compared to either agent alone 4
• This combination is particularly effective because the response to amlodipine is independent of baseline renin activity, while lisinopril's effect is renin-dependent 4
• Available as fixed-dose combination (Lotrel) 1

Additional Combination Options for Specific Conditions

Beta-Blockers (Especially in Heart Failure or Post-MI)

• Carvedilol, metoprolol succinate, bisoprolol, or nebivolol should be used together with lisinopril in patients with heart failure with reduced ejection fraction 1
• Beta-blockers are first-line treatment along with ACE inhibitors for NYHA class I-IV heart failure 1
• This combination has been shown to reduce deaths by 38 per 1000 patient-years when beta-blockers are added to ACE inhibitors 1

Aldosterone Receptor Antagonists (In Heart Failure)

• Spironolactone 12.5-25 mg once daily or eplerenone can be added to lisinopril in heart failure patients with reduced ejection fraction (<40%) 1
• This combination prevents 57 deaths per 1000 patient-years of treatment 1
• Critical monitoring requirement: Serum potassium must be monitored frequently when combining these agents with lisinopril 1
• Do not use if: serum creatinine ≥2.5 mg/dL in men or ≥2.0 mg/dL in women, or serum potassium ≥5.0 mEq/L 1

Hydralazine Plus Isosorbide Dinitrate

• This combination can be added to lisinopril in African American patients with NYHA class III or IV heart failure with reduced ejection fraction 1
• Important caveat: Hydralazine should never be used without a nitrate in heart failure patients 1

Medications to AVOID With Lisinopril

Absolute Contraindications

• Do NOT combine with other ACE inhibitors or ARBs (dual RAAS blockade) - this increases risk of hypotension, hyperkalemia, and renal dysfunction without additional benefit 1
• Avoid aliskiren (direct renin inhibitor) - combination with ACE inhibitors is contraindicated, especially in diabetes or renal insufficiency 1

Relative Contraindications in Heart Failure

• Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) should be avoided in heart failure with reduced ejection fraction 1
• Clonidine, moxonidine, and hydralazine without nitrate are contraindicated in heart failure with reduced ejection fraction 1
• Alpha-blockers (doxazosin) should only be used if other agents are inadequate at maximum tolerated doses 1

Practical Algorithm for Adding Medications to Lisinopril

1. If blood pressure remains uncontrolled on lisinopril 40 mg daily (maximum dose), add a second agent rather than exceeding this dose 5

2. First choice: Add hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg once daily 1, 5

3. If diuretic contraindicated or ineffective: Add amlodipine 5-10 mg once daily 1, 4

4. If patient has heart failure: Ensure beta-blocker is on board, then consider adding spironolactone 12.5-25 mg with close potassium monitoring 1

5. Monitor closely for:

   • Hypotension (hold lisinopril if systolic BP <90 mmHg) 6
   • Hyperkalemia (especially with aldosterone antagonists or in renal impairment) 1
   • Renal function deterioration (small increases in creatinine are expected and acceptable) 1

Common Pitfalls to Avoid

• Do not use dual RAAS blockade (ACE inhibitor + ARB, or ACE inhibitor + aliskiren) - this was common practice but is now known to cause harm 1
• Do not continue adding lisinopril beyond 40 mg daily - add a second agent instead 5
• Do not combine with NSAIDs when possible, as they reduce antihypertensive efficacy and worsen renal function 1
• Do not add aldosterone antagonists without frequent potassium monitoring, especially in patients with any degree of renal impairment 1