A Review of Lisinopril in the Treatment of Heart Failure

Shannon Marsh, RN, BSN, CCRNMSNE 5356Advanced PharmacologyDr. Elizabeth LongA Review of Lisinopril in the Treatment of Heart Failure

Heart Failure and Lisinopril

Heart failure is a common condition treated in the critical care setting. The registered nurse caring for the patient suffering from heart failure will likely be administering an ACE inhibitor such as lisinopril. Lisinopril has been shown to be very effective in treating and even preventing heart failure in patients.2

Heart Failure and the RAASHeart FailureThe Renin-Angiotensin-Aldosterone SystemInability of the heart to effectively pump and/or fill (Porth, 2015)Compensatory mechanisms activated (including the RAAS)Initial increase in cardiac output, but increases the workload on the heart in the long-run.Vicious cycle continues (Arcangelo & Peterson, 2013).

In heart failure, blood flow to the kidneys is decreased, which activate the RAAS.Angiotensin II: A potent vasoconstrictor (Increases afterload)Aldosterone: Retains sodium and water (Increases preload)All increase the hearts workload, leading to decreased renal blood flow, and the cycle continues (Porth, 2015; Arcangelo & Peterson, 2013).

If the ejection fraction is decreased in the heart failure patient, blood flow to major body organs will be decreased, including the kidneys. The kidneys will then activate the renin-angiotensin-aldosterone system, or RAAS. The RAAS, along with other compensatory mechanisms activated, will initially increase cardiac output. However, over time, this will only lead to increase work for the heart. A heart that is failing cannot deal with the increased workload. The result is an even further decrease in ejection fraction, more decreased blood flow to the kidneys and other organs, and more stimulation of the RAAS and other compensatory mechanisms.In the RAAS, renin is released, which stimulates the activation of angiotensin I. With the help of an enzyme, angiotensin I then converts to angiotensin II. Angiotensin II is a potent vasoconstrictor. The vasoconstriction increases blood pressure and afterload for the heart. Aldosterone is also released, which leads to the retention of sodium and water. This increases the preload for the heart. Again, increased workload will eventually damage the heart even further and continue the heart failure cycle.3

Response of Lisinopril when Treating Heart FailureLisinopril binds to receptor sites on the angiotensin converting enzyme, blocking the conversion of angiotensin I to angiotensin II.This equals less vasoconstrictionAldosterone levels are also decreased.This equals less sodium and water retention (PDR.net, 2017).Lisinopril also decreases the signs of heart failure: dyspnea, heart failure, orthopnea, fatigue, and peripheral edema (Arcangelo & Peterson, 2013).

This is where lisinopril comes in. Lisinopril acts on the enzyme that converts angiotensin I to angiotensin II. This blocks the conversion of angiotensin I to angiotensin II, leading to a decrease in vasoconstriction. Decreasing vasoconstriction decreases afterload on the heart. When angiotensin II levels are decreased, aldosterone levels are decreased as well. A decrease in aldosterone will lead to a decrease in sodium and water retention and a decrease in cardiac preload. Lisinopril and other ACE inhibitors also treat the symptoms of heart failure, such as the ones listed here, and make exercise more tolerable for the patient.4

Response of Lisinopril (Continued)The ATLAS study:Higher doses of lisinopril = reduced morbidity and mortality in heart failure patients (Packer et al., 1999).

The Assessment of Treatment with Lisinopril and Survival, or ATLAS, study observed the effects of low doses of lisinopril compared to higher doses of lisinopril. The researchers compared the morbidity and mortality rates of patients taking low doses of lisinopril, such as 2.5-5mg daily, with the morbidity and mortality rates of patients taking higher doses of lisinopril, such as 32.5-35mg daily. Their findings showed that higher doses reduced the morbidity and mortality of heart failure patients.5

Response of Lisinopril (Continued)Hypertension is a risk factor for developing heart failure (Arcangelo & Peterson, 2013).In a study by Brilla, Funck, and Rupp (2000), hypertensive patients taking lisinopril for 6 months showed decreased myocardial fibrosis.Therefore, lisinopril may be beneficial for preventing heart failure in hypertensive patients.

Hypertension is a modifiable risk factor for heart failure. Hypertension can lead to myocardial fibrosis, left ventricular hypertrophy, and eventually HF. In one study, patients suffering from hypertension who were treated with lisinopril for six months showed a decrease in myocardial fibrosis. Therefore, lisinopril may be useful in not only treating heart failure, but preventing it in hypertensive patients.6

Pharmacist ConsultationPotential InteractionsAdverse Drug Reactions and Side EffectsIncreased hypotensive effect when taken with antipsychotics, barbiturates, and loop diuretics.Increased risk for hyperkalemia when taken with heparin or a potassium sparing diuretic.May not be safe to take with an ARB.HypotensionDizzinessAngioedema (serious)Hyperkalemia(P. Austin, personal communication, February 6, 2017; Epocrates, 2017).

To learn more about lisinopril, I conducted an interview with a critical care pharmacist. During the interview, potential drug interactions were discussed. Hypotension was mentioned as a potential drug interaction that could occur if lisinopril is taken with antipsychotics, barbiturates, or loop diuretics. Hyperkalemia could also occur if the patient is taking lisinopril with heparin or a potassium sparing diuretic. The pharmacist also stated that ACE inhibitors and ARBs may not be safe to take together, and the physician and patient should collaborate on which drug would be best for the patient to take.Adverse drug reactions and side effects included hypotension, dizziness, hyperkalemia, and angioedema. Angioedema is a serious side effect, and lisinopril should be discontinued if this occurs.7

Pharmacist Consultation (Continued)PharmacokineticsOnset: 1 hourPeak: 6 hoursDuration: 24 hoursNot metabolizedExcreted by kidneys in urine as unchanged drugHalf-life: 12 hours(P. Austin, personal communication, February 6, 2017; Epocrates, 2017).

According to the pharmacist, the onset of lisinopril is 1 hour, the drug peaks at about 6 hours, and its duration is 24 hours. The drug is not metabolized in the body and is excreted by the kidneys into the urine as unchanged drug. The half-life of the drug is 12 hours.8

Protein Binding

Negligible protein binding!

Trbojevic-Stankovic, Aleksic, and Odovic (2015); RxList.com (2017)

Lisinopril has almost 0% protein binding. Therefore, all or almost all of the drug is unbound, or free to act on its target receptor sites. This means that other drugs that are highly protein bound will likely not have an effect on the displacement of lisinopril Because there is nothing to displace!9

PharmacogenomicsIncreased risk of ischemic stroke and angioedema in African AmericansAngiotensin Type 1 Receptor Gene (AGTR1) is being studied- no results yet (Johnson, 2008).There is a lack of research on the effects of lisinopril on African Americans.More research is needed.Physicians need to discuss pharmacogenomics with their clients.

In regards to pharmacogenomics, some research on lisinopril shows an increased risk of ischemic stroke and angioedema in African American patients when compared with whites or Hispanics. The Angiotensin Type 1 Receptor Gene is currently being studied, but no consistent findings have been discovered yet.There is still a lack of research on the effects of lisinopril on other races, especially African Americans. More research is needed in this field, and physicians should discuss pharmacogenomics with their clients and how it may affect them.10

Pharmacist Consultation: Ideas to Improve Communication and Patient Care

Review the patients serum creatinine and serum potassium and report them to the physician if they are high.Lisinopril should never be used in pregnancy.It may be better to have once-a-day dosing rather than BID (P. Austin, personal communication, February 6, 2017).

During the interview with the pharmacist, ideas on how to improve communication and patient care in regards to patient safety were discussed. The pharmacist said to report to the physician if the patients serum creatinine and potassium and elevated. This could cause serious adverse events for the client. Also, the pharmacist stated that many people do not know that lisinopril should never be used in pregancy. Serious harm or even death to the developing fetus could occur if used in pregnancy. Lastly, if you look at the pharmacokinetics of lisinopril, you will notice that the duration of the drug is 24 hours, yet many physicians continue to order the drug BID, or twice a day. It is not likely that twice a day will have any beneficial effects for the patient. In fact, twice a day dosing may contribute to cost, pill burden, and decreased patient compliance. Once daily dosing may be better for the patient.11

Synthesis of FindingsLisinopril reduces preload and afterloadLisinopril can help reduce heart failure symptoms (Arcangelo & Peterson, 2013).Hypotension, hyperkalemia, and angioedema could occur (there are other adverse effects too)

I plan to advocate for my heart failure clients by ensuring the physician prescribes an ACE inhibitor such as lisinopril!

In conclusion, we have discussed the pathophysiology of heart failure and how lisinopril can treat this condition. We now know that the patient on lisinopril is at risk for hypotension, hyperkalemia, and angioedema. It is also clear that lisinopril is an effective drug for treating heart failure, and in my own practice, I plan to advocate for my patients with heart failure by ensuring they are on an ACE inhibitor such as lisinopril.12

ReferencesArcangelo, V. & Peterson, A. (2013). Pharmacotherapeutics for advanced practice (3rd Ed.)Philadelphia, PA: Lippincott, Williams, & Wilkins.Brilla, C. G., Funck, R. C., & Rupp, H. (2000). Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation, 102, p. 1388-1393.Epocrates, Inc. (2017). Epocrates premium. Retrieved from https://online.epocrates.com/homeJohnson, J. A. (2008). Ethnic differences in cardiovascular drug response: Potential contribution of pharmacogenetics. Circulation, 118(13), p. 1383-1393.Packer, M., Poole-Wilson, P. A., Armstrong, P. W., Cleland, J. G. F., Horowitz, J. D., Massie, B.M., Ryden, L., Thygesen, K., & Uretsky, B. F. (1999). Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity andmortality in chronic heart failure. Circulation, 100, p. 2312-2318.PDR.net (2017). Lisinopril- drug summary. Retrieved from http://www.pdr.net/drug summary/Prinivil-lisinopril-376Porth, C. M. (2015). Essentials of Pathophysiology (4th Ed.). Philadelphia, PA: Wolters Kluwer.Trbojevic-Stankovic, J., Aleksic, M., & Odovic, J. (2015). Estimation of angiotensin-converting enzyme inhibitors protein binding decrease using chromatographic hydrophobicity data. Srp Arh Celok Lek, 143(1-2), p. 50-5.

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