22 Spotlight on Bleeding Management nt
Pharmacy Practice News • April 2015
Tirofiban Switch Yields Savings—and Debate T
he jury is still out on the leading glycoprotein IIb/IIIa inhibitor (GPI). Medical studies, guideline changes and drug pricing have convinced some hospitals to select tirofiban over others in the class. Although these centers report saving hundreds of thousands of dollars, some pharmacists continue to express concern that outcomes from the drug have not been measured sufficiently. Pharmacists at Intermountain Medical Center in Murray, Utah, five years ago performed an analysis comparing the total cost of tirofiban (Aggrastat, Medicure) with eptifibatide (Integrilin, Millennium) for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI) such as angioplasty or stent placement. Their results, presented at the American College of Clinical Pharmacy’s annual meeting in 2009, estimated that by switching from eptifibatide to tirofiban, the medical center could save about $400,000 annually with no detriment to the approximately 3,000 patients with ACS treated there each year. After making the switch in early 2013, the medical center saved $250,000 that year and $350,000 in subsequent years, said Katy Mathews Cox, PharmD, who led the transition at Intermountain but is now a cardiac transplant pharmacist at Baylor University Medical Center, in Dallas. Patient outcomes are still being collected, Dr. Cox said, but the cost savings were reported at the American College of Cardiology’s (ACC) annual scientific session in March. Other medical centers have made similar choices. In 2012, clinicians at Emory University, in Atlanta created an ACS algorithm using a highdose bolus of tirofiban as the preferred GPI; the algorithm was rolled out to all four of Emory’s hospitals by 2014. The change resulted after Medicure representatives approached the hospital in early 2012 with newer data for tirofiban, Emory interventional cardiologist Michael McDaniel, MD, told Pharmacy Practice News. Around the same time, the hospital was trying to standardize practices for conditions like ACS, and Dr. McDaniel was part of a multidisciplinary working group looking at this area. “Although the ACC/American Heart Association [AHA] guidelines are helpful, they allow for different options for different situations,” Dr. McDaniel said. Emory’s cardiology leaders asked
the group to pinpoint a single best therapy to maximize value in each scenario, with the term “value” encompassing safety, efficacy and cost of therapy, he said. They compared data for the two GPIs on their formulary, eptifibatide and abciximab (ReoPro, Janssen), with that for tirofiban.
2009;53[18]:1668-1673; Circ Cardiovasc Interv 2009;2[3]:230-236), he said, and the 2011 PCI guidelines “give a similar recommendation for all three GPIs in STEMI.” Registry data also show similar efficacy among the drugs, he said. The only area where tirofiban was not similar was cost, Dr. McDaniel said;
STEMI Cardiac Catheterization Lab Protocol
ACT, activated clotting time; GPI, glycoprotein IIb/IIIa inhibitor; PCI, percutaneous coronary intervention; PO, oral; STEMI, ST segment elevation myocardial infarction
The protoc ol they developed (Crit Pathw Cardiol 2013;12[3]: 141-149) rec ommends the use of high-dose tirofiban but no other GPI agents for conditions like STEMI, with the rationale driven largely by cost considerations, Dr. McDaniel said. Although early studies using lower doses of tirofiban suggested it was inferior to other GPIs regarding platelet inhibition and outcomes ((Am J Cardiol 2002;89[12]:647-650; N Engl J Med d 2001;344[25]:1888-1894), “more contemporary studies using higher loading doses and infusions have demonstrated that tirofiban is equally efficacious as other GPIs,” he noted ((Am Heart J 2007;154:344 e1-344.e5; Am J Cardiol 2006;97[4]:489-493; JAMA 2008;299[15]:1788-1799). Meta-analyses in STEMI patients suggested that tirofiban resulted in similar outcomes like ST resolution and Thrombolysis in Myocardial Infarction (TIMI) 3 flow compared with abciximab ((Am J Cardiol 2010;106[2]:167-174; J Am Coll Cardiol
it was quite lower than the others. By switching, Emory halved the money spent on GPIs, said Collin Lee, PharmD, the assistant director of pharmacy at Emory. In 2011, the institution spent about $500,000 on GPIs; in 2014, the total was about $225,000. There was some holdout from physicians at Emory’s community hospitals who were used to using eptifibatide and didn’t want to switch, “but they eventually did because of cost savings and the need for market share,” Dr. Lee said. A lot of that resulted from people “just being comfortable with what they know,” Dr. McDaniel said.
High-Dose Bolus In October 2013, the FDA approved a supplemental new drug application for a high-dose bolus regimen of tirofiban (25 mcg/kg over three minutes, followed by 0.15 mcg/kg/min for up to 18 hours) for the reduction of thrombotic cardiovascular events in patients with non-ST elevated ACS, spurring additional buzz on pharmacy listservs. The high-dose bolus is recommended in the ACC/AHA guideline for unstable angina/non-ST elevation myocardial infarction (Circu-
lation 2012;14[7];126:875-910) and the ACC/AHA/Society for Cardiac Angiography and Interventions guideline for PCI (Circulation 2011;124[23]:e574-e651), and has been evaluated in at least 30 studies in more than 8,000 patients, according to a Medicure press release. But not everyone has jumped on the bandwagon. Paul Dobesh, PharmD, an associate professor of pharmacy practice at the University of Nebraska Medical Center’s College of Pharmacy in Omaha, said that pharmacists should use caution when making these kinds of substitutions. “It’s not like there has been this big study that says now tirofiban at this dose is just as good, or noninferior, to these other agents,” said Dr. Dobesh, whose medical center does not use tirofiban. As for the studies that have been done on tirofiban, Dr. Dobesh noted that they have used “surrogate end points” such as time to ST segment resolution or improvement in TIMI flow. “Although these are typically solid end points, they have failed us in the past, and so it’s really a leap of faith,” he said. “To take that leap just to save some money, we’re not adequately considering the patient.” Clinicians who want to use tirofiban in ACS patients should demand more rigorous outcomes studies, Dr. Dobesh added. Medicure is enrolling patients in the SAVI-PCI (Shortened Aggrastat vs Integrilin in Percutaneous Coronary Intervention) clinical trial, which will assess a high-dose bolus of tirofiban plus a shortened infusion duration compared with label-dosing eptifibatide in patients undergoing PCI to look at composite rate of death, PCI-related myocardial infarction, urgent target vessel revascularization or in-hospital major bleeding within 48 hours following PCI or hospital discharge, according to clinicaltrials.gov. Dr. Cox said that many of the changes affecting use of tirofiban “have been driven by new studies becoming available, and guideline updates,” she said, with such information helping to validate expert opinion about the GPI. “Not to mention tirofiban now has FDA approval for high-dose bolus [therapy],” she said. “The reality is that the true highrisk ACS population (STEMI, high-risk NSTEMI) has been studied more with high-dose bolus tirofiban versus doublebolus eptifibatide. I have new appreciation for knowing the literature, because it has affected how much money we saved and how we manage these patients.” —Karen Blum Dr. McDaniel is a consultant for Medicure. Dr. Cox has received speaking fees as a clinical consultant for Medicure. Dr. Dobesh reported no relevant financial conflicts of interest.