Value in the Cath Lab: Contemporary Use of GP IIb/IIIa Inhibitors in the Treatment of ACS at the Mayo Clinic Heath System

Has the Mayo Clinic Health System established a standardized acute coronary syndrome (ACS) treatment protocol?

Yes. There is a system-wide protocol for the inpatient management of ACS patients, although there are some ways for individuals to tailor it to individual patients. 

How do glycoprotein (GP) IIb/IIIa inhibitors fit within this protocol?

Over the years, use of GP IIb/IIIa inhibitors has certainly changed quite a bit. About 10 years ago, I was the director of inpatient cardiology at another institution, and at that time, the use of GP IIb/IIIa inhibitors for non-ST elevation patients was quite high. GP IIb/IIIa usage is not as common now. Less than 10% of the patients in our inpatient service are being managed with, or are on, a GP IIb/IIIa inhibitor. In the cath lab, it depends on the situation. For stable angina patients, again, a decade and a half ago, it was not uncommon to see the use of GP IIb/IIIas in high-risk lesions and high-risk patients. Today, in our cath lab and in many cath labs around the United States, using GP IIb/IIIa inhibitors for stable patients is not a common occurrence. For the non-ST elevation ACS patient, there is still a role for GP IIb/IIIa inhibitors. There is a Class I indication if no up-front, dual antiplatelet therapy was administered. If people do receive dual antiplatelet therapy up front, which is true for the majority of our patients, GP IIb/IIIa use is a Class II indication. We don’t routinely use GP IIb/IIIa inhibitors for our non-ST elevation ACS patients in the cath lab unless we see a high thrombus burden, which I would say is in less than 20% of our cases. One area where I do see GP IIb/IIIa inhibitors widely used, at least in our institution, is in ST-elevation myocardial infarction (STEMI) patients. STEMIs usually involve quite a large thrombus burden, and while it is not routine for us to use GP IIb/IIIa inhibitors on all of our STEMI patients, which is what we did a decade ago, their use is common. More than 50% of our patients get a GP IIb/IIIa inhibitor if they present with a STEMI, because in our patient population, given their age and the time at which they present, usually there is quite a large thrombus burden in the arteries. 

Could you briefly describe the mechanistic attributes of GP IIb/IIIa inhibitors?

In the cath lab, we are all worried about platelets as one of the big players involved in thrombosis, and there are many agents that we use to inhibit platelet action and aggregation, such as aspirin and the thienopyridines (oral P2Y12 inhibitors). The benefit of GP IIb/IIIa inhbitors is that they inhibit a common pathway, the final mechanism of platelet aggregation. So while aspirin, clopidogrel, and other P2Y12 agents inhibit platelets up front, the GP IIb/IIIa inhibitors inhibit the final common pathway of platelet aggregation, thus making them a powerful antiplatelet tool. 

Is the shift in the use of GP IIb/IIIa inhibitors over time reflected in what is being taught at your hospital?

Yes. It has always been the case that we want to make sure patients have adequate antiplatelet therapy at the time of their procedure in the cath lab. Obviously, the greater the risk of thrombosis (i.e., STEMI patients), the more antiplatelet action we want to have on board. Fortunately, oral antiplatelet agents have become more mainstream. Many of our patients already come into the cath lab with up-front dual antiplatelet therapy. That being said, there are cases where patients do not receive up-front dual antiplatelet therapy or where they only recently received oral antiplatelet agents, meaning they may not be fully inhibited in terms of platelet action. We want to make sure that these patients are adequately inhibited and thus would use GP IIb/IIIa inhibitors. Teaching has changed over the years to reflect the favoring of oral agents up front rather than the use of intravenous IIb/IIIa inhibitors up front.

Can you describe the adoption of tirofiban within your system?

The adoption was similar to a lot of things that have been going on in the cath lab recently. Historically in the cath lab, GP IIb/IIIa use has involved eptifibatide (Integrilin) and abciximab (ReoPro), because the prior clinical trials showed that those were the most efficacious agents. While both are GP IIb/IIIa inhibitors, their mechanism is slightly different in terms of their structure. Abciximab is a monoclonal antibody and eptifibatide is a small-molecule agent. Over time, tirofiban (Aggrastat) dosing changed to the higher dose bolus, which has been shown to be more efficacious in terms of clinical outcome. Now, in the cath lab, we have three GP IIb/IIIa inhibitors that we can use, two of which, tirofiban and eptifibatide, are both small molecule. As a result, cath labs are going to have to consider whether they need to have three different GP IIb/IIIa inhibitor agents in their lab. Abciximab, because it is a monoclonal antibody, will always have a role, especially in people with renal failure on dialysis, which describes a significant number of our patients, as we are a renal transplant center. Thus, we will always have abciximab on the formulary. We then are left with two small-molecule agents, which with the new high-bolus dosing for tirofiban, are essentially similar in efficacy. You then have to ask yourself which one is better from a financial point of view. It is similar to how many cath labs no longer have every brand of drug-eluting stent on their shelf. They tend to have a contract where they can get the best pricing. We have had to utilize the same principles when looking at which GP IIb/IIIa inhibitor to have on board. So we looked at pricing, which was more in favor of tirofiban, and that was the reason we made the change from eptifibatide. 

In the era of dual antiplatelet therapy, can short infusion GP IIb/IIIas be used as a means to decrease bleeding risk while still providing ischemic protection?

There are some data, but not large, prospective, randomized trials. There is some decrease in bleeding rate with the shorter infusions, but I don’t think you can definitively say either way.

Can you elaborate on how the Mayo Clinic Health System makes formulary decisions on therapeutics?

Mayo Clinic has three main areas: the midwest, the southeast, and the southwest, and multiple hospitals within each of those areas. Each hospital is its own entity, but in terms of supplies, we try to maximize efficiency as well as cost savings. We refer to our overall system as an “enterprise,” which includes all of the Mayo sites, formularies, and equipment decisions. For each field, such as cardiovascular, there is a committee that meets on an enterprise level and that works to consolidate our equipment and pharmaceutical use. This committee works to standardize care for best practices and also attempts to control pricing. It is a fairly large-size committee with multiple representatives, both physician as well as allied health staff. When decisions are made, such as the decision to move to tirofiban, it usually occurs through a committee, be it a single meeting or multiple meetings, and voting. It is not an individual decision by any one or even multiple persons, but a variety of individuals from different backgrounds that are involved in the care of patients. No one single entity can make a change without the agreement of the group as a whole. 

How is the implementation of a changed therapy or product addressed on your individual hospital level?

It depends on the issue and situation. We usually try to involve the team in the decision-making process also. In this particular instance, we had discussed the clinical effectiveness as well as the cost usage issues of tirofiban vs eptifibatide with the team, and decided that we would, as a group, go along with the change. The implementation is obviously multi-step. We have the nursing staff in the cath lab, the nursing staff on the floor, as well as the mid level providers and the physicians and fellows, so it is multi-tiered. Fortunately, the move to tirofiban is not a major change. 

How long has it been?

It has been about 6 weeks since we changed here. 

Has there been a financial benefit for your hospital from the adoption of tirofiban?

As an individual entity here in Arizona, as well as a larger enterprise, we have not had enough data or time to analyze yet, so I think it would be premature to say. 

Are cost considerations being taught to fellows?

It has become more of an issue. In the past, many fellows, when they left training, probably worked for an independent entity (a single or multi-specialty group). Today, as more and more cardiologists become hospital-employed, the cost of the procedure becomes relevant. In the past, if you were independent, you would come in, do the procedure, and receive the physician reimbursement. The hospital thanked you for bringing your patient to them, and they dealt with the facility fees and the costs of your procedure. Today, if you are hospital employed, you need to control some of those resource uses to help minimize costs.

Any final thoughts?

Overall, GP IIb/IIIa inhibitor use has decreased in the cath lab due to the administration of oral antiplatelet therapy up front. In terms of choosing which GP IIb/IIIa inhibitor to use, what historically has just been a two-person game, is now a three-person game that includes abciximab, eptifibatide, and tirofiban. Two of these GP IIb/IIIa agents, eptifibatide and tirofiban, are similar in structure and properties and we have to assume, based on the clinical data, that the efficacy is also similar. The nature of the modern-day cath lab is that decision-making is driven by pricing. You can’t have every piece of equipment any more. You have to decide on which ones you need. Decisions have to be efficacious for patients, but also keep cost in mind. 

Disclosure: Dr. Eric Yang reports no conflicts of interest regarding the content herein.

Eric H. Yang, MD, can be contacted at yang.eric@mayo.edu.