Norton Healthcare Transitions Primary GP IIb/IIIa Inhibitor to Tirofiban

While glycoprotein (GP) IIb/IIIa inhibitor use during percutaneous coronary intervention (PCI) has declined over the past decade, do you find there remains an appropriate setting for a GP IIb/IIIa inhibitor in contemporary practice in terms of prevention and resolution of thrombotic complications?

GP IIb/IIIa inhibitor use has been changing over the last 10 years, but in current practice, where I think it fits in best is in troponin-positive acute coronary syndrome (ACS) patients, in particular, ST-elevation myocardial infarction (STEMI) and non-STEMI patients. An additional area where a GP IIb/IIIa inhibitor may be useful is in multi-vessel PCI and stenting of long segments, especially when the patient has not been pretreated with a P2Y12 inhibitor.

Is the risk of stent thrombosis a factor?

Fortunately, stent thrombosis has been decreasing over the past 15 years for multiple reasons, which is reassuring. It hasn’t reached zero and is a concerning event for all interventional cardiologists. Patient outcomes are considerably worse for stent thrombosis, along with the costs associated with it. We need to optimize patient care to prevent it. 

How do you balance ischemic protection provided by using a GP IIb/IIIa inhibitor and the associated bleeding risk? 

The patients we are treating are older, frail, and with more comorbidities in general, so this is becoming a bigger issue. As a result, there has been increasing awareness of the need to try to balance ischemic and bleeding complications. It has been done in a variety of ways, but some pertain to our pharmacology use, in terms of eliminating our use of GP IIb/IIIa inhibitors in certain situations or reducing the infusion duration. Bivalirudin has a role in some populations of patients and has been very popular. The slow transition to the transradial approach has also mitigated some of the bleeding complications that are unique to the femoral approach.

Have you adopted a short infusion strategy?

I have always believed that most of the benefit from GP IIb/IIIa use comes during the intervention and perhaps for 2-4 hours afterwards, at which time the oral P2Y12 inhibitors are being absorbed and becoming systemically available. So I never saw much benefit for more prolonged GP IIb/IIIa infusion, except in certain rare situations of residual thrombus or side branch occlusion. I have always used a shorter infusion strategy and more recently, have moved to a bolus-only approach for most patients. Reducing the duration of the infusion still preserves the benefit but decreases the bleeding risk.

There has been some discussion of delayed onset of the newer P2Y12 inhibitors. What evidence do we have and could a fast-onset GP IIb/IIIa inhibitor address this issue?

I think the clinical evidence for this is limited. There are a lot of patients who have slow absorption or don’t ideally absorb oral P2Y12 drugs in the acute setting, particularly those patients who are nauseated or who have delayed gastric emptying for various reasons around the time of a PCI procedure.

Do you consider the possibility of a delayed onset for oral P2Y12 inhibitors when using a GP IIb/IIIa?

I do. I am most concerned after the procedure is completed, up to 4 hours post procedure. Additional drugs that are active in that immediate post PCI window would be beneficial. Therefore, the bolus and short-infusion strategy of a GP IIb/IIIa inhibitor becomes very helpful, because it covers that window when platelet inhibition is not optimal and there is risk for an acute stent thrombosis. 

Why did Norton Healthcare system choose tirofiban as its primary GP IIb/IIIa inhibitor?

I initially became aware of the cost differences with regard to tirofiban and other available GP IIb/IIIa inhibitors. Upon further review, I saw there were multiple other advantages to tirofiban that would be helpful in our process of using this class of drugs. It seemed like a good transition to make.

What were some of those advantages?

In particular, tirofiban’s method of storage, the single bolus as opposed to the two-bolus approach with eptifibatide, the ability to use tirofiban in patients with more advanced renal insufficiency, the drug delivery from a staff standpoint, and also, the cost differential compared to the other available agents.

When did the Norton Healthcare system transition to tirofiban as their primary GP IIb/IIIa?

The process was started in the fall of 2016 and we had it in place to use in approximately March of this year. I began reviewing all of the literature available, potential advantages to the system, and how we would best go about implementing it. Norton Healthcare is a regional healthcare provider predominantly centered around Louisville. They have 4 hospitals, 3 of which do PCI. There were three hospitals involved in the switch that perform PCI. They all switched to tirofiban at the same time.

How did the availability of the concentrated bolus vial format impact the decision to switch to tirofiban?

It is an advantage in the sense that it is a single bolus. The staff doesn’t need to give it over 10-minute separate intervals; the drug can all be given at once. The time it takes to get the full effect is a little quicker when it is given as a single bolus. It is also much simpler for staff in terms of programming the pumps and the way the drug is packaged.

What education was offered?

We have a very strong pharmacy department. After the decision was made, we asked the pharmacy & therapeutics committee to make the transition to tirofiban, and they prepared the in-services for staff and all the logistical arrangements for having the drug available. It was a smooth transition.

Was there any hesitation from staff or physicians during the transition?

No. I went to all my partners and discussed it with each of them to see what they thought about switching and how it might impact their practices. There are 12 interventional cardiologists in our practice. There were some questions, but no real reservations. Once I had gotten a consensus, I took it forward to the managing director of the service line, who then took it to the pharmacy & therapeutics committee, and it went forward from there. There were some questions along the way, which we were able to answer from the available literature, but no real objections. 

Have you been able to quantify cost savings?

The amount of GP IIb/IIIa use has been decreasing compared to years past, so I believe the numbers are less than the original estimate, but I was initially told it was to be on the order of $250,000/year.

What do you see moving forward?

Awareness of optimizing pharmacology is important, but there is a lot of individual variation with how people approach this issue. Tirofiban is a good option. More and more people are becoming better aware of it, and should consider it for use in their practice.

Do you have advice for other centers that may be considering a switch to tirofiban?

The impetus needs to come from the physicians. Ideally, someone should take the issue to their partners and get a consensus from that standpoint. Taking it forward from there is much easier when the physicians have a uniform opinion about making a change. There are, to my knowledge, no real disadvantages to making a switch. Once physicians are comfortable that it is providing better, more cost-efficient care for patients, the remainder of the process is much easier. 

Disclosure: Dr. Divyesh Bhakta reports no conflicts of interest regarding the content herein.

Dr. Bhakta can be contacted at bhakta.divyesh@gmail.com.