Is lisinopril (Zestril) acceptable for treating hypertension?

Is Lisinopril Acceptable for Treating Hypertension?

Yes, lisinopril is an excellent and FDA-approved first-line agent for treating hypertension in adults and children ≥6 years of age, with proven efficacy in reducing cardiovascular morbidity and mortality. 1

FDA-Approved Indications

Lisinopril is specifically indicated for:

• Treatment of hypertension to lower blood pressure, which reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions 1
• Heart failure to reduce signs and symptoms of systolic heart failure 1
• Post-myocardial infarction mortality reduction in hemodynamically stable patients within 24 hours of acute MI 1

Guideline-Based Recommendations for Hypertension

General Hypertension Management

Lisinopril (an ACE inhibitor) is recommended as a first-line antihypertensive agent, particularly when specific compelling indications exist. The choice between drug classes should be guided by:

• Compelling indications for ACE inhibitors include heart failure, left ventricular dysfunction, Type I diabetic nephropathy, Type II diabetic nephropathy, and chronic renal disease 2
• Blood pressure targets: Aim for <140/85 mm Hg in non-diabetic patients and <140/80 mm Hg in diabetic patients (optimal targets are even lower at <130/80 and <130/75 respectively) 2

Comparative Efficacy

The ALLHAT trial demonstrated that lisinopril had similar efficacy to chlorthalidone (thiazide diuretic) and amlodipine (calcium channel blocker) in preventing coronary and cardiovascular events, though it was less effective than thiazide diuretics in preventing heart failure 2

Important caveat: In Black patients, ACE inhibitors like lisinopril are less effective as monotherapy compared to thiazide diuretics or calcium channel blockers for stroke prevention and heart failure prevention 2. In these patients, consider starting with a thiazide diuretic or adding one to lisinopril.

Special Populations Where Lisinopril Excels

Heart Failure with Reduced Ejection Fraction (HFrEF)

ACE inhibitors like lisinopril are Class I, Level of Evidence A recommendations for patients with hypertension and HFrEF 2. They should be used together with:

• Beta-blockers (carvedilol, metoprolol succinate, bisoprolol, or nebivolol) 2
• Aldosterone receptor antagonists 2
• Thiazide or thiazide-type diuretics for blood pressure control 2

Heart Failure with Preserved Ejection Fraction (HFpEF)

For HFpEF patients with persistent hypertension after volume management, ACE inhibitors should be prescribed and titrated to achieve SBP <130 mm Hg (Class I, Level C-LD recommendation) 2

Coronary Artery Disease

In patients with coronary heart disease and hypertension, lisinopril is equally effective as other major drug classes (thiazide diuretics, calcium channel blockers) in preventing cardiovascular events 2. The ALLHAT trial specifically showed similar outcomes between lisinopril, chlorthalidone, and amlodipine in hypertensive coronary patients 2

Diabetic Nephropathy

Lisinopril provides renoprotective effects superior to calcium channel blockers, diuretics, and beta-blockers in diabetic patients with nephropathy, without adversely affecting glycemic control 3. It is effective in both:

• Hypertensive patients with IDDM or NIDDM and microalbuminuria or overt renal disease 3
• Normotensive patients with IDDM and microalbuminuria (as shown in the EUCLID trial) 3

Renal Impairment

Lisinopril can be used safely in patients with renal impairment, but dose adjustment is required:

• Start with 2.5 mg daily if GFR <30 ml/min 4, 5
• Start with 5 mg daily if GFR 30-60 ml/min 4, 5
• Monitor renal function closely, especially when combined with other RAAS inhibitors or in the presence of renal insufficiency 2
• Do not use if serum creatinine ≥2.5 mg/dL in men or ≥2.0 mg/dL in women when combining with aldosterone antagonists 2

Contraindications and Cautions

Absolute contraindications:

• Pregnancy 2
• History of angioedema with ACE inhibitors 2

Use with caution in:

• Peripheral vascular disease (due to association with renovascular disease) 2
• Bilateral renal artery stenosis 6
• Severe renal impairment (requires dose adjustment) 2
• When combined with aldosterone antagonists, monitor potassium frequently and avoid if serum potassium ≥5.0 mEq/L 2

Practical Dosing Algorithm

Starting dose:

• 5-10 mg once daily for most patients 1, 7
• 2.5 mg once daily if GFR <30 ml/min 4, 5

Titration:

• Increase dose every 2-4 weeks based on blood pressure response 7
• Maximum dose: 40 mg once daily 1, 4
• Peak effect occurs at 6 hours, with antihypertensive effect lasting 24 hours 7
• Steady state achieved in 2-3 days 7

If inadequate response:

• Add a thiazide diuretic (hydrochlorothiazide), which produces approximately additive blood pressure lowering effects 7
• In Black patients, consider adding a thiazide diuretic or calcium channel blocker earlier 2

Common Pitfalls to Avoid

• Do not combine with ARBs: This increases adverse effects without additional benefit 6
• Monitor for first-dose hypotension: Especially in volume-depleted or salt-depleted patients 1
• Avoid NSAIDs when possible: Indomethacin and other NSAIDs reduce the antihypertensive effect of lisinopril 1
• Do not use nondihydropyridine calcium channel blockers (verapamil, diltiazem) in HFrEF: These are Class III Harm recommendations 2
• Monitor potassium levels: Especially when combined with aldosterone antagonists, other potassium-sparing agents, or in renal impairment 2, 1

Key Advantages of Lisinopril

• Once-daily dosing improves adherence 1, 7
• Does not cause hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia 7
• Maintains or increases renal blood flow 7
• Does not directly reduce heart rate, which may be advantageous when bradycardia would be problematic 8
• Not metabolized and excreted unchanged in urine, reducing drug-drug interactions 1, 7