From the Guidelines
Lisinopril, an Angiotensin-Converting Enzyme (ACE) inhibitor, is recommended to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) due to its established benefits in reducing symptoms and improving survival, as evidenced by large randomized controlled trials (RCTs) 1.
Mechanism of Action and Effects
Lisinopril works by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby relaxing blood vessels and reducing blood pressure. This mechanism not only helps in managing hypertension but also in reducing the workload on the heart, which is beneficial for patients with heart failure. The use of ACE inhibitors like Lisinopril has been shown to reduce morbidity and mortality in patients with HFrEF, with or without coronary artery disease 1.
Clinical Use and Recommendations
The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors, like Lisinopril, is recommended for patients with chronic HFrEF to reduce morbidity and mortality 1. It is advised to start Lisinopril at low doses and titrate upward to doses shown to reduce the risk of cardiovascular events in clinical trials. However, caution is advised in patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium, as ACE inhibitors can produce angioedema and should be used with caution in these populations 1.
Side Effects and Monitoring
Common side effects of Lisinopril include dry cough, dizziness, headache, and fatigue. More serious but rare side effects include angioedema and hyperkalemia. Regular monitoring of kidney function and potassium levels is recommended while taking this medication 1. It is also crucial to avoid the use of ACE inhibitors during pregnancy due to the potential harm they can cause to the developing fetus 1.
Comparison with Other Therapies
While Angiotensin Receptor-Neprilysin Inhibitors (ARNI) have been found to be superior to ACE inhibitors in some aspects for the treatment of HFrEF, ACE inhibitors like Lisinopril remain a strongly advised treatment option for all classes of HFrEF, especially for those patients for whom ARNI is not appropriate 1. Angiotensin Receptor Blockers (ARBs) are recommended for patients intolerant to ACE inhibitors due to cough or angioedema, highlighting the importance of individualizing treatment based on patient tolerance and response 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. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion.
The effect of Lisinopril, an Angiotensin-Converting Enzyme Inhibitor, is to:
- Decrease plasma angiotensin II
- Decrease vasopressor activity
- Decrease aldosterone secretion This results in a reduction of blood pressure in patients with hypertension, primarily through suppression of the renin-angiotensin-aldosterone system 2 2.
From the Research
Effects of Lisinopril on Hypertension
- Lisinopril is effective in lowering blood pressure in all grades of essential hypertension, with dosages of 20 to 80 mg once daily being effective 3.
- It is at least as effective as usual therapeutic dosages of hydrochlorothiazide, atenolol, metoprolol, and nifedipine in reducing blood pressure 3.
- Lisinopril reduces total peripheral resistance, maintains or improves cardiac contractility, promotes regression of left ventricular hypertrophy, and increases renal blood flow 4.
Effects of Lisinopril on Congestive Heart Failure
- Lisinopril improves indices of cardiac function and appears to produce greater benefit than captopril in patients with congestive heart failure resistant to conventional therapy 3.
- 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 reducing the risk of major clinical events in patients with heart failure 5.
- Lisinopril increases exercise duration, improves left ventricular ejection fraction, and has no significant effect on ventricular ectopic beats in patients with congestive heart failure 6.
Effects of Lisinopril on Myocardial Infarction
- Lisinopril reduces mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment 7.
- The GISSI-3 trial demonstrates that lisinopril produces measurable survival benefits within 1 to 2 days of starting treatment, with reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) at 6 weeks 7.
Tolerability and Safety
- Lisinopril is well tolerated, with few serious adverse effects being reported 3.
- The most common adverse events occurring in recipients of the drug are dizziness, headache, hypotension, and diarrhoea 5.
- Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily, and may be less costly than other members of its class 7.