By Jennifer Chou, Pharm.D., PGY1 pharmacy resident, Detroit Medical Center, Harper University Hospital 

Cardiovascular disease is the leading cause of death globally, and approximately one in three deaths in the United States is from heart disease, stroke or other cardiovascular diseases.¹ There has been a decline in mortality rates for patients experiencing myocardial infarction (MI) with ST-segment elevation (STEMI) due to improvements in initial therapy, which includes fibrinolysis and percutaneous coronary intervention (PCI).² Prompt revascularization with PCI following acute coronary syndrome (ACS) is essential to minimize myocardial ischemia and improve chance of survival. PCI consists of balloon angioplasty with or without stenting and is preferred if a skilled interventional cardiologist and catheterization laboratory are available.²

The 2011 American College of Cardiology Foundation (ACCF)/American Heath Association (AHA)/Society for Cardiac Angiography and Intervention (SCAI) Guideline for PCI has specific recommendations regarding antiplatelet use before and during PCI. Antiplatelet therapy with P2Y₁₂ receptor inhibitors is a cornerstone of therapy in PCI with stenting. By blocking P2Y₁₂ receptors located on platelet surfaces, these agents inhibit adenosine diphosphate (ADP)-induced platelet activation and aggregation.⁴ Loading doses of a P2Y₁₂ receptor inhibitor are recommended as an adjunct to PCI with stenting, as follows: 1) Clopidogrel 600 mg (300 mg if fibrinolytic therapy within past 24 hours), 2) Prasugrel 60 mg or 3) Ticagrelor 180 mg.⁵ The TRITON-TIMI 38 trial compared prasugrel to clopidogrel in patients with ACS and found that prasugrel was associated with improved clinical outcomes, but also an increased rate of major hemorrhage.⁶ In the PLATO study comparing ticagrelor to clopidogrel in patients with ACS, ticagrelor was associated with reduced vascular and all-cause mortality and an increase in major bleeding, transient dyspnea and bradycardia.⁷  Prasugrel and ticagrelor have a faster onset of action (15 minutes-one hour) and increased platelet inhibition (61-95 percent) compared to clopidogrel (one-two hours and 30-65 percent, respectively).⁸ Although prasugrel and ticagrelor have demonstrated improved clinical outcomes, the cost of these agents limits their use on an outpatient basis.

GP IIb/IIIa inhibitors are IV agents that block platelet GP IIb/IIIa receptors, inhibiting the final step in platelet aggregation. Abciximab and eptifibatide are the formulary agents used as an adjunct to PCI at the Detroit Medical Center (DMC) in situations such as inadequate loading with a P2Y₁₂ receptor inhibitor or thrombotic complications during PCI. Tdsads Trials evaluating various GP IIb/IIIa inhibitors showed a reduction in ischemic complications in patients undergoing PCI, but earlier trials suggested an increased bleeding risk.^9-12 These studies were conducted prior to the availability of prasugrel and ticagrelor, which subsequently led to reductions in the use of GP IIb/IIIa inhibitors.

Cangrelor (Kengreal^®) is a Food and Drug Administration-approved IV nonthienopyridine reversible P2Y₁₂ receptor inhibitor used as an adjunct to PCI. Cangrelor has a rapid onset of action (15-30 minutes), as well as a rapid off-set, with the level of platelet inhibition returning to baseline within one hour of discontinuation.⁸ The CHAMPION PHOENIX Trial compared cangrelor 30 μg/kg bolus followed by 4 μg/kg/min for at least two hours or the duration of the procedure (whichever is longer) to clopidogrel 300 mg or 600 mg loading dose in patients undergoing PCI for ACS.¹³ Cangrelor significantly reduced the composite rate of death, myocardial infarction, ischemia-driven revascularization and stent thrombosis at 48 hours with no significant difference in severe bleeding.¹³ In a pooled analysis of three major trials comparing cangrelor to clopidogrel or placebo, cangrelor significantly reduced thrombotic complications for up to 30 days but increased the risk of mild bleeding.¹⁴

The Detroit Medical Center added cangrelor to its inpatient formulary with specific criteria for use as an adjunct to PCI. Only an interventional cardiologist would place the order, and patients must have impaired oral antiplatelet absorption (severe gastroparesis, intractable vomiting) or have the inability to take an oral antiplatelet by mouth. For conversion to oral agents, ticagrelor 180 mg may be administered anytime during the infusion or immediately after discontinuation of the infusion. Recall that ticagrelor binds reversibly to the P2Y1₂ receptor, so clopidogrel 600 mg and prasugrel 60 mg must be given immediately after discontinuation of the infusion. This difference is due to the irreversible binding of clopidogrel and prasugrel to the P2Y1₂ receptor. Cangrelor competes for the same binding site, preventing the thienopyridines from binding. When cangrelor dissociates from the receptor, the active metabolites of clopidogrel and prasugrel have already been hydrolyzed and are no longer available (owing to their short half-life).

GP IIb/IIIa inhibitors and P2Y₁₂ receptor inhibitors are available therapies as an adjunct to PCI. Use of GP IIb/IIIa inhibitors is restricted to specific situations and is increasingly less common. Among the P2Y₁₂ receptor inhibitors, cangrelor now provides an intravenous option useful in select patient populations. Careful consideration of the benefits, risks and individual factors should be performed before using cangrelor as an adjunct to PCI.

References

1. Mozaffarian D, Benjamin EJ, Go AS, et al; Heart Disease and Stroke Statistics – 2015 Update: A Report from the American Heart Association. Circulation. 2016;133(4):e38-360.
2. Keeley EC, Hillis LD. Primary PCI for Myocardial Infarction with ST-Segment Elevation. N Engl J Med 2007;356:47-54.
3. Nallamothu BK, Bradley EH, Krumholz HM. Time to Treatment in Primary Percutaneous Coronary Intervention. N Engl J Med 2007;357:1631-8.
4. Kengreal (cangrelor) [prescribing information]. Parsippany, NJ: The Medicines Company; June 2015.
5. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e574-e651.
6. Wiviott SD, Braunwald E, McCabe CH, et al; for the TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–15.
7. Wallentin L, Becker RC, Budaj A, et al; for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–57.
8. Wallentin L. P2Y₁₂ inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 2009;30(16):1964-77.
9. The EPILOG Investigators. Platelet Glycoprotein IIb/IIIa Receptor Blockade and Low-Dose Heparin during Percutaneous Coronary Revascularization. N Engl J Med 1997;336:1689-1697.
10. Valgimigli M, Percoco G, Barbieri D, et al. The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial. J Am Coll Cardiol 2004;44(1):14-9.
11. The ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037-44.
12. The EPIC Investigators. Use of a Monoclonal Antibody Directed against the Platelet Glycoprotein IIb/IIIa Receptor in High-Risk Coronary Angioplasty. N Engl J Med 1994;330:956-961.
13. Bhatt DL, Stone GW, Mahaffey KW, et al; for the CHAMPION PHOENIX Investigators. Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events. N Engl J Med 2013;368:1303-13.
14. Steg PG, Bhatt DL, Hamm CW, et al; for the CHAMPION Investigators. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013;382:1981–92.

By Joel D. West, Pharm.D., pharmacy manager, Spectrum Health – Zeeland Community Hospital

The opportunity to implement a new inventory management system within my hospital pharmacy was met with a certain level of excitement mixed with nervousness. I thought, “Will this technology actually do what it says it can? How well will it fit within current workflows? How well will it integrate with existing technologies? Will the expense be justified?” I knew that in any event, a sound implementation strategy was required. Talking with fellow users helped gain perspective, but with all the differences between my hospital pharmacy and fellow users, this only took me so far.

Looking back, I wish there was more literature available around the real benefits of the system, what went well during implementation and the lessons learned. So here it is: My brief experience with implementing an inventory management system.

To set the stage, I currently work at a 57-bed community hospital in West Michigan that is part of a 12 hospital system. We implemented an inventory management system along with upgrading its current automated dispensing cabinets. The main benefits to adding this technology were related to patient safety and inventory management efficiencies.

Benefits

Pharmacy supply chain is a complex set of processes, especially when variation is added into the equation. With all of this variation, we believed we could significantly decrease on-hand inventory with this standardization, but could we expect a 70 percent reduction like the vendor had previously seen? While a 70 percent reduction has not fully panned out, we have seen significant improvements.

Our inventory management system provided new opportunities to assign minimum and maximum inventory levels ultimately standardizing reorder points. This gives all staff the same ordering expectations in order to prevent over or under ordering. Standardizing the product purchased within the system helped to ensure the same product is ordered each time, regardless of the staff who submitted the order. Ensuring the same product is ordered each time decreases the number of products added to our other technologies thereby saving time. Reporting data has also allowed us to track usage more closely and use this data for updating and improving inventory all while providing usage data to staff to help prevent hoarding behaviors. Reporting data has allowed us to track usage more closely. This data has been used for improving inventory and to help educate staff about preventing hoarding behaviors.

Barcode Medication Administration has long been a layer of safety built into the medication use cycle to decrease medication administration errors. This technology has also been used in retail settings and some inpatient pharmacies for years but was not a part of our current practice. This additional barcode scan during receipt, restocking and dispensing includes a further layer of safety by ensuring the right product is picked prior to leaving the pharmacy. Barcode driven supply chain improved safety and helped create a closed loop perpetual inventory system which decreased on-hand inventory costs.

Successes

Staff engagement is the single biggest factor in the success at our facility. We needed to share how this technology will make staff’s life easier, and how it will make our patients safer. These are key conversations to have with end-user stakeholders to not only help during the implementation stage but also with continuous improvement of the system. We are most successful when the end-user becomes the expert and works to make the system even better than when it comes “out of the box.”

Communication goes hand-in-hand with staff engagement. With any new system there are improvements that commonly come with a change in practice or additional steps. It is common for leadership to share that this new technology will solve all of the staff’s problems, only to find out that it does not and, at times, adds more work or complexity to their daily tasks. In order to show both respect for the staff members as well as the great work that they do, sharing the benefits of the system and the workflow changes early on will help to accomplish this.

Our finance team works closely with us while using this software to keep watch on the trends of inventory and related expenses. We use a cycle count methodology to ensure our perpetual inventory is accurate and get an inventory snapshot on a quarterly basis to see how we stack up to previous inventory levels. This is a great way to teach finance for a pharmacy supply chain and hold the pharmacy accountable to continuous improvement.

Lessons Learned

Contracting is a tedious, yet mission critical step in the process. This is the first step that can make or break a project from the beginning. Although pricing is often at the forefront of the contracting conversation, understanding contractual intricacies and the vendor value proposition are of equal importance. When negotiating the contract, be very specific in what is included such as server hardware, workstations and peripheral equipment. These are all good questions to ask so that four months into the project, you do not have to ask your executive team for more money for servers or other types of hardware, which were not included in the original agreement.

Before you sign the contract, think about how the hardware will work in your space. Many of these technologies use Bluetooth^® communication which struggles to make it through the cinderblock walls of most basement pharmacies which may ultimately require additional hardware to make it operational. Data ports are always something that is an afterthought and can be sometimes very difficult to add later. Keep these things in mind as you work through your plan. Remember, you can never over plan.

Throughout the planning and implementation process, accurate local data is critical. This data ranges from medication usage trends all the way to interfacing identification. With this breadth of data requirements, having a local data expert who knows the pharmacy systems can be an invaluable resource to the project, not to mention decrease data collection through spreadsheet manipulation.

During the continuous improvement phase of the project, ask staff what they would improve with the system and focus on the pain points. Asking these questions creates a common ground on which the department can improve.

Through this implementation, there have been many benefits, successes and lessons learned. I trust that this glimpse into our story will help guide you as you look to implement technology within your pharmacy around inventory management.