What is the effect of Lisinopril (Angiotensin-Converting Enzyme Inhibitor)?

From the Guidelines

Lisinopril is recommended as a first-line treatment for patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, as evidenced by the 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure 1.

Key Points to Consider

• Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to reduce morbidity and mortality in patients with HFrEF, with or without coronary artery disease 1.
• The medication should be started at a low dose and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials, with caution in patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium 1.
• Common side effects of lisinopril include dry cough, dizziness, headache, and rarely angioedema, and patients should be monitored for these adverse effects 1.
• Lisinopril is generally well-tolerated, but patients should be aware of potential interactions with other medications, such as potassium supplements, NSAIDs, and lithium 1.

Important Considerations

• Patients with prior or current symptoms of chronic HFrEF should be treated with ACE inhibitors, such as lisinopril, to reduce morbidity and mortality, unless they are intolerant to ACE inhibitors due to cough or angioedema 1.
• In patients who are intolerant to ACE inhibitors, angiotensin receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs) may be considered as alternative treatments 1.
• The use of ACE inhibitors, including lisinopril, is beneficial for patients with HFrEF and has been shown to reduce morbidity and mortality in large randomized controlled trials 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system.

The mechanism of action of Lisinopril is the inhibition of angiotensin-converting enzyme (ACE), which leads to a decrease in the conversion of angiotensin I to angiotensin II, resulting in decreased vasopressor activity and aldosterone secretion.

• The beneficial effects of Lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system 2.
• Lisinopril is antihypertensive even in patients with low-renin hypertension.

From the Research

Overview of Lisinopril

• Lisinopril is an orally active angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension and congestive heart failure 3.
• It is effective in lowering blood pressure in all grades of essential hypertension, with dosages of 20 to 80 mg once daily 3.
• Lisinopril is at least as effective as other ACE inhibitors, such as enalapril and captopril, in improving symptomatic end-points and clinical status in patients with heart failure 4.

Efficacy in Hypertension

• Lisinopril is effective in reducing blood pressure in elderly patients with hypertension, with response rates of 68.2 to 89.1% 5.
• Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day 5.
• Lisinopril can be used as a first-line treatment for hypertension, either alone or in combination with other medications, such as hydrochlorothiazide 3.

Efficacy in Congestive Heart Failure

• Lisinopril improves indices of cardiac function and reduces the risk of major clinical events in patients with congestive heart failure 4.
• High doses of lisinopril (32.5 to 35mg, administered once daily) demonstrate clinically important advantages over low doses (2.5 to 5mg, administered once daily) in the treatment of congestive heart failure 4.
• Lisinopril is at least as effective as other ACE inhibitors, such as enalapril and captopril, in improving symptomatic end-points and clinical status in patients with heart failure 4.

Efficacy in Acute Myocardial Infarction

• Lisinopril reduces mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment 6.
• The GISSI-3 trial demonstrated that lisinopril, given orally within 24 hours of symptom onset and continued for 6 weeks, produces measurable survival benefits within 1 to 2 days of starting treatment 6.
• Lisinopril confers ongoing benefit after drug withdrawal, with a 6.2% reduction in the incidence rate for the combined end-point of death or severe left ventricular dysfunction at 6 months 6.

Comparison with Other Treatments

• Lisinopril is at least as effective as other ACE inhibitors, such as enalapril and captopril, in improving symptomatic end-points and clinical status in patients with heart failure 4.
• Lisinopril is also effective in reducing blood pressure and improving outcomes in patients with hypertension, compared to other medications such as thiazide diuretics and calcium channel blockers 7.
• The choice of ACE inhibitor appears less important than the decision to treat, with benefits likely being a class effect 6.