What is lisinopril?

What is Lisinopril?

Lisinopril is a long-acting angiotensin-converting enzyme (ACE) inhibitor administered once daily that blocks the formation of angiotensin II, thereby lowering blood pressure and improving cardiac function while maintaining perfusion of vital organs. 1, 2

Drug Classification and Mechanism

• Lisinopril is the lysine analogue of enalaprilat (the active metabolite of enalapril) and belongs to the nonsulfhydryl class of ACE inhibitors characterized by weak chelating properties. 2, 3
• Unlike captopril (which contains a sulfhydryl group), lisinopril's chemical structure makes it less likely to cause certain side effects like skin rashes, taste abnormalities, and blood dyscrasias that are characteristic of sulfhydryl-containing drugs. 2
• The drug produces maximum pharmacodynamic effects 6 to 8 hours after administration, with effects persisting for 12 to 24 hours, allowing for convenient once-daily dosing. 4

FDA-Approved Indications

Lisinopril has three primary FDA-approved uses: 1

1. Hypertension: Treatment in adults and pediatric patients 6 years and older to lower blood pressure, which reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. 1

2. Heart Failure: Reduction of signs and symptoms of systolic heart failure when added to diuretics and/or digoxin. 1, 4

3. Acute Myocardial Infarction: Reduction of mortality in hemodynamically stable patients within 24 hours of acute MI, used alongside standard treatments like thrombolytics, aspirin, and beta-blockers. 1, 3

Dosing Guidelines by Indication

For Hypertension:

• Starting dose: 5-10 mg once daily (2.5 mg if GFR <30 ml/min, 5 mg if GFR 30-60 ml/min). 5, 6
• Typical effective range: 10-40 mg once daily. 5, 6
• Maximum dose: 40 mg once daily. 7

For Heart Failure:

• Starting dose: 2.5-5 mg once daily. 7, 8
• Target dose: 20-40 mg once daily, with evidence supporting higher doses for superior outcomes. 7, 8
• The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) reduced death or hospitalization by 12% and heart failure hospitalizations by 24% compared to low doses (2.5-5 mg daily). 8, 4
• Titration should occur at intervals of not less than 2 weeks, with monitoring of blood pressure, renal function, and potassium. 8

Key Adverse Effects and Monitoring

Common Class Effects (occur with all ACE inhibitors):

• Cough: Occurs in up to 20% of patients but rarely requires discontinuation; if persistent and troublesome, consider switching to an ARB. 7, 2
• Hypotension: Particularly with initial doses in volume-depleted patients or those on diuretics. 8, 4
• Hyperkalemia: Monitor potassium levels, especially when combined with potassium-sparing diuretics or supplements. 8, 2
• Renal function changes: An increase in creatinine up to 50% above baseline is acceptable when initiating therapy. 8

Serious Adverse Effects:

• Angioedema: Occurs in fewer than 1% of patients but is more frequent in Black patients; this is a life-threatening reaction that warrants permanent discontinuation of all ACE inhibitors. 7
• ACE inhibitors should never be initiated in any patient with a history of angioedema. 7

Clinical Advantages

• Effective in difficult-to-treat populations: Well-tolerated and effective in elderly patients and those with renal impairment. 5, 3, 6
• Renal protection: Demonstrated benefits in diabetic nephropathy with reductions in albuminuria. 3
• Post-MI mortality reduction: The GISSI-3 trial showed lisinopril reduced mortality and left ventricular dysfunction when started within 24 hours of MI onset, with similar benefits in elderly and younger patients. 3
• Cost-effectiveness: Economic studies suggest lisinopril is cost-saving compared with other ACE inhibitors in some markets. 3

Important Clinical Caveats

• Lisinopril may be administered alone or with other antihypertensive agents, and many patients will require more than one drug to achieve blood pressure goals. 1
• The drug should be combined with diuretics in patients with current or recent fluid retention to maintain sodium balance. 9
• Lisinopril should not be initiated in hypotensive patients at immediate risk of cardiogenic shock. 9
• Dosages need to be lower in patients with significant renal impairment (starting at 2.5 mg if GFR <30 ml/min). 5