The Role of the Nurse in Treating Patients With INTEGRILIN (eptifibatide) Injection

Why is the role of the nurse in the treatment of acute coronary syndrome (ACS) patients so critical?

Nurses play a key role in the care of ACS patients. The nurse is the healthcare provider at the patient’s bedside 24/7, assessing, diagnosing, planning, implementing, and evaluating care.¹ At every entry point in the healthcare system, nurses are utilizing their triage and decision-making skills to provide the best possible care for the best possible patient outcomes. Triaging of potential ACS cases requires skills in rapid assessment and risk stratification.

Throughout a patient’s hospital stay, the nurse functions as one of the primary healthcare providers, responsible for continuous monitoring of the patient’s clinical status, rhythm status, ischemic events, drug responses, laboratory and diagnostic findings, and education on disease process. The nurse expedites communication of findings to the physician and other appropriate team members.¹ Based on clinical assessment and communication, the risk level and therapeutic plan of care may change.

Rapid assessment and provision of evidence-based care is key to positive outcomes for patients. While nursing care during the acute event is vital, the cardiac nurse also participates in quality improvement activities, clinical research, and registry data collection to enhance knowledge and improve practice for all ACS patients.¹

Indications for INTEGRILIN^® (eptifibatide) Injection:

• For the treatment of patients with acute coronary syndrome (unstable angina/non-ST-elevation myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI)
• For the treatment of patients undergoing PCI, including those undergoing intracoronary stenting²

Patients who receive the glycoprotein IIb/IIIa inhibitor INTEGRILIN (eptifibatide) have a reduced risk of ischemic events, but carry a risk of bleeding.² What can be done to try to reduce the risk of bleeding?

It is important for all individuals receiving an intravenous antithrombotic agent, such as the GP IIb/IIIa inhibitor eptifibatide, to have an individualized risk assessment prior to initiation of therapy to identify those at greatest risk for bleeding complications. According to the Global Registry of Acute Coronary Events (GRACE Registry), factors and patient characteristics associated with a higher risk for bleeding include:   

• Advanced age (elderly);
• Female gender;
• Prior history of bleeding;
• Renal insufficiency;
• Use of certain pharmacological and mechanical therapeutic interventions.³

To try to reduce the risk of bleeding, the nurse also must ensure that appropriate doses of antithrombotic agents, such as unfractionated heparin (UFH), are given based on individualized patient variables.⁴ Antithrombotics, such as GP IIb/IIIa inhibitors, should be dosed based on the patient’s renal function and body weight.⁵ It is advised that creatinine clearance be considered to assess renal function.⁶ Normal serum creatinine levels are possible in the presence of reduced renal function.⁷ Individuals undergoing PCI with a creatinine clearance ≥ 50 mL/min can be given standard doses of eptifibatide: 180 mcg/kg bolus followed by a continuous infusion of 2 mcg/kg/min and a second 180 mcg/kg bolus 10 minutes after the first bolus. Those with decreased creatinine clearance (< 50 mL/min) should receive the same bolus doses; however, the continuous infusion must be reduced to 1 mcg/kg/min.² In addition, activated clotting time (ACT) levels should be monitored closely during PCI. According to the INTEGRILIN prescribing information, while patients are receiving heparin, target ACT levels should be maintained between 200–300 seconds during PCI.²

Nurses are encouraged to initiate and maintain bleeding precautions, particularly at the vascular access site.⁸ Vascular punctures, injections, and catheter insertions should be minimized.² Nurses caring for PCI patients are encouraged to understand the type, extent, and complexity of the procedure so that they are able to recognize potential vascular-related complications. Complications observed should be reported to the physician as soon as they are recognized.⁹ Appropriate postprocedure diagnostic and laboratory tests should be performed.⁹

Another strategy to try to reduce the risk of bleeding is to ensure early sheath removal.8 Heparin should be discontinued with reversal of effects before pulling sheaths. ACT levels should be < 150 seconds or activated PTT (aPTT) < 45 seconds before sheath removal.² Manual or mechanical compression of the access site should be maintained until hemostasis is achieved, with the nurse monitoring vital signs.¹⁰ Additionally, nurses should promote comfort measures, including pain management and appropriate activity level (avoid using sandbags and allow patient to choose position of comfort, whether supine or a 30-degree angle).⁸ Nurses should feel empowered to communicate their assessment findings as needed, challenge nonguideline-based care, and advocate for evidence-based therapies.¹ Lastly, nurses are encouraged to provide simple, continuous education to their patients to increase knowledge and promote healthy lifestyle changes postdischarge.¹¹

Selected Safety Information

INTEGRILIN Is Contraindicated in Patients With:

• A history of bleeding diathesis or evidence of active abnormal bleeding within the previous 30 days
• Severe hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg) not adequately controlled on antihypertensive therapy
• Major surgery within preceding 6 weeks
• History of stroke within 30 days or any history of hemorrhagic stroke
• Current or planned administration of another parenteral GP IIb/IIIa inhibitor
• Dependency on renal dialysis
• Known hypersensitivity to any component of the product²

What should nurses be considering when using eptifibatide in high-risk non-ST-elevation (NSTE) ACS patients?

When I think of high-risk NSTE ACS patients, I think of individuals who have the most to lose, in terms of their heart function, and the most to gain by evidence-based therapies. High-risk patients include those with elevated cardiac markers (CK-MB/troponin), renal insufficiency, diabetes, electrocardiogram (ECG) changes suggesting ischemia, and the elderly.^5,12 We now have a more clear understanding of the risk that diabetes poses with enhanced platelet aggregation and cardiovascular disease.¹³ We also have learned the value of early, continuous ST segment monitoring for identification of ongoing ischemic events and risk stratification.¹⁴ Ischemic monitoring is now part of the ACS clinical practice guidelines.¹⁵ Nurses are encouraged to understand evidence-based clinical guidelines and advocate for their implementation in the ACS population.¹ Application of evidence-based guidelines has led to a marked decrease in in-hospital rates of heart failure, cardiogenic shock, recurrent MI, and in 6-month rates of death and stroke.⁵

Why is knowledge of renal function important in patients receiving eptifibatide?

Approximately 50% of eptifibatide is excreted via the kidneys;² therefore, knowledge of renal function is important to try to reduce potential complications, particularly bleeding.¹⁶ Serum creatinine is a frequently assessed parameter, but, as I mentioned earlier, is not the best laboratory test for determining overall kidney function.⁶ Serum creatinine is influenced by individual muscle mass and dietary habits.⁶ Creatinine clearance estimation, by way of the Cockcroft-Gault equation, was used to estimate renal function and gauge eptifibatide dosing in clinical trials.² Creatinine clearance approximates glomerular filtration rate (GFR), the best overall index of renal function, as outlined by the National Kidney Foundation.⁶ Use of serum creatinine levels alone to determine renal function may be misleading⁶ because serum creatinine levels can remain normal in the presence of reduced renal function.⁷ Individuals with reduced creatinine clearance (< 50 mL/min) should receive the same bolus doses of eptifibatide; however, they must have the infusion dose reduced from 2 mcg/kg/min to 1 mcg/kg/min.²

Selected Safety Information

Selected Warnings and Precautions

• Bleeding is the most common complication encountered during INTEGRILIN^® (eptifibatide) therapy. The majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal, and retroperitoneal bleeding were also seen more commonly with INTEGRILIN compared to placebo.
• If bleeding cannot be controlled with pressure, infusion of INTEGRILIN and concomitant heparin should be stopped immediately.
• INTEGRILIN is cleared in part by the kidney and its plasma concentrations are doubled in patients with renal disease (creatinine clearance < 50 mL/min). Therefore, the infusion dose of INTEGRILIN needs to be reduced to 1 mcg/kg/min in these patients. 
• In the event of acute profound thrombocytopenia or a confirmed platelet decrease to < 100,000/mm³, discontinue INTEGRILIN and heparin (UFH or low-molecular-weight heparin). 
• There has been no clinical experience with INTEGRILIN initiated in patients with a baseline platelet count < 100,000/mm³. If a patient with low platelet counts is receiving INTEGRILIN, their platelet count should be monitored closely.
• In patients undergoing PCI, INTEGRILIN is associated with an increase in major and minor bleeding at the site of arterial sheath placement. Special care should be employed to minimize the risk of bleeding among these patients.
• Because INTEGRILIN inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect hemostasis, including thrombolytics, oral anticoagulants, NSAIDs, and dipyridamole.
• Use with other GP IIb/IIIa inhibitors should be avoided.²

Bleeding is a risk with GP IIb/IIIa inhibitors. What is the nurse’s role in addressing this risk?

Nurses are in a key position to implement strategies that try to reduce the risk of bleeding in patients receiving GP IIb/IIIa inhibitors. Prior to administering such agents, nurses should identify individuals who may have contraindications for such therapy and communicate this information to team members.¹⁰ Contraindications to eptifibatide use include a history of bleeding disorders, severe hypertension, recent major surgery, history of stroke, administration of another parenteral GP IIb/IIIa inhibitor, renal disease requiring dialysis, or hypersensitivity to eptifibatide.²

ACS registries have reported that NSTE ACS patients have often received higher than recommended doses of antithrombotic agents.¹⁷ In particular, females, the elderly, and those individuals with renal insufficiency have been identified as the most likely to receive excess doses.¹⁷ Nurses can assist in ensuring that correct doses of these agents are given to reduce the incidence of adverse effects.

For additional information, see the Brief Summary of the Prescribing Information on the following page.

Disclosure: Ms. Housholder-Hughes serves as a member of the speakers bureau for Merck. She can be contacted at shoushol@med.umich.edu.

Merck has paid for and provided input for this article.

References

1. Housholder-Hughes S. Non-ST-segment elevation acute coronary syndromes: management strategies for optimal outcomes. Crit Care Nurse. 2006;(suppl):S8–S36.
2. INTEGRILIN® (eptifibatide) Injection [prescribing information]. Kenilworth, NJ: Schering Corporation; 2011.
3. Moscucci M, Fox KAA, Cannon CP, et al. Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J. 2003;24:1815–1823.
4. Melloni C, Alexander K, Chen A, et al. Unfractionated heparin dosing and risk of major bleeding in non-ST-segment elevation acute coronary syndromes. Am Heart J. 2008;156:209–215.
5. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction. J Am Coll Cardiol. 2007;50:1–157. 
6. National Kidney Foundation. www.kidney.org/professionals/KLS/gfr.cfm. Accessed July 5, 2011.
7. Giannelli S, Patel KV, Windham BG, et al. Magnitude of underascertainment of impaired kidney function in older adults with normal serum creatinine. J Am Geriatr Soc. 2007;55(6):816–823. 
8. Juran N, Rouse CL, Smith DD, et al. Nursing interventions to decrease bleeding at the femoral access site after percutaneous coronary intervention. Am J Crit Care. 1999;8:303–313.
9. Shoulders-Odom B. Management of patients after percutaneous coronary intervention. Crit Care Nurse. 2008;28:26–41.
10. Huber C. Safety after cardiac catheterization: minimizing vascular complications. Am J Nurs. 2009;109(8):57–58. 
11. Duryee R. The efficacy of inpatient education after myocardial infarction. Heart Lung. 1992;21:217–225.
12. Kumar A, Cannon C. Acute coronary syndromes: diagnosis and management, part 1. Mayo Clin Proc. 2009;84:917–938.
13. Natarajan A, Zaman A, Marshall S. Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents. Diabetes Vasc Dis Res. 2008;5:138–144.
14. Yan A, Yan R, Tan M, et al. Long-term prognostic value and therapeutic implications of continuous ST-segment monitoring in acute coronary syndrome. Am Heart J. 2007;153:500–506. 
15. Bassand JP. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28:1598–1660.
16. Selvakumar S. Renal dysfunction following myocardial infarction. Annals of Medicine and Healthcare Research. 2009;101–114.
17. Alexander K, Chen A, Roe M, et al. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA. 2005;294:3108–3116.