August 9th, 2010

The GP IIb/IIIa Inhibitor Wars: Not Ready To Surrender


Although two recent studies (EVA-MI and SCAAR) report that eptifibatide is as effective as abciximab with respect to myocardial reperfusion and clinical events in patients undergoing primary PCI, the thoughtful and balanced editorial accompanying them points out that the studies “ought not be considered convincing or as level 1 evidence” that the GP IIb/IIIa inhibitors have similar effectiveness in this patient population.

I asked Peter Berger, the author of the editorial, about how he thinks we should use  IIb/IIIa inhibitors. Here is our exchange:

1. Is there any role for use of GP IIb/IIIa inhibitors outside of the catheterization laboratory?

From everything I know, there ought to be only a very limited role for upstream IIb/IIIa inhibitors. I would recommend a IIb/IIIa upstream of the cath lab in a patient who is at low risk of bleeding, in whom cath is planned but cannot be performed for at least many hours, and who, despite maximal medical therapy including IV nitroglycerin and a P2Y12 inhibitor, is having rest angina with marked ST changes (i.e., ST depression). Where I practice at Geisinger Clinic, such a patient would go to the cath lab immediately because it is open 24 hours a day, 7 days a week. Where immediate cath cannot be performed, I believe that a IIb/IIIa inhibitor would probably improve clinical outcome in such a patient.

2. In the patients undergoing PCI, are we spending too much time, effort, and money preventing “microinfarctions?” Should we even be concerned about them?

For years I believed that more attention has been paid to microinfarctions than is appropriate. That opinion used to be in the minority; I don’t think it is any longer. The association between such infarctions and late adverse events is weak, and patients with large infarctions and failed procedures were often not excluded from analyses linking procedural infarctions and late adverse events. While microinfarctions can’t possibly be good for patients, whether and how bad they are remains unclear. The placebo-controlled IIb/IIIa inhibitor trials revealed a >30% reduction in such infarctions, yet a tiny, 0.4% late difference in mortality; this actually supports, I believe, the argument against a strong causal link between such infarctions and late adverse events. This is especially true when one considers that most deaths in these trials occurred months after a <24-hour infusion, that most deaths in the placebo arms occurred in patients who had not suffered a procedural MI, and that no credible mechanism by which these drugs would reduce death months after their use has been widely accepted, let alone confirmed.

3. If you were having an acute MI and undergoing primary PCI, would you want to receive a GP IIb/IIIa inhibitor/antibody? If so, which one? Would your choice be modified if you were paying for it “out of pocket?”

I rarely recommend IIb/IIIa inhibitors in STEMI patients, and even then only in patients who are at low risk of bleeding and high risk of thrombotic complications; for example, patients who have a large thrombus burden in a major vessel. When I do recommend them, I am more driven by efficacy than cost (which reflects what I would want for myself, as well). I think the data are strongest for abciximab, but about a half-dozen undersized studies suggest that the higher bolus dose of tirofiban might be as efficacious as abciximab. (Note: I serve on advisory boards for both Lilly, which makes and markets abciximab, and Medicure, which makes and markets tirofiban.)

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