Off-label use of familiar PCI drug results in fewer bleeds

Occasionally, off-label use can be as safe and effective than the originally approved method, sometimes more so. This appears to be the case for eptifibatide, according to a study published online Feb. 5 in Circulation: Cardiovascular Interventions.

When used according to the drug label, the glycoprotein IIb/IIIa inhibitor eptifibatide (Integrilin, Millennium Pharmaceuticals) is administered as a double bolus during PCI and then as a post-PCI infusion.

Little has been done to change this labeling since the drug was first approved by the FDA. However, Hitinder S. Gurm, MD, of the University of Michigan Medical Center in Ann Arbor, and colleagues have noted this isn’t necessarily how the drug is used in all cases. Some physicians who administer eptifibatide forgo the post-PCI drip.

To investigate in-hospital outcomes, Gurm et al looked at data from hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium for PCIs performed between 2010 and 2011. They found 21.2 percent of patients in the period were given bolus-only, with rates of standard, on-label treatment varying from 35 to 100 percent across different hospitals.

Compared with standard treatment, this off-label use of eptifibatide resulted in fewer bleeds (2.3 percent vs. 2.7 percent). Off-label treatment also resulted in lower transfusion rates (2.7 percent vs. 3.8 percent). Mortality and vascular complication rates were low and similar for both groups.

Bolus-only treatment not only decreased the overall risk of bleeding (odds ratio 0.74), but significantly decreased risk for gastrointestinal bleeding (odds ratio 0.40). There was no increase in risk for thrombotic events using the bolus-only method.

They noted that not only was this method safe and effective, but cost-effective, by using less drug over the course of patient treatment.

Matthew W. Sherwood, MD, MHS, and James E. Tcheng, MD, both of Duke University Health System in Durham, N.C., wrote that studies like this prove that “the package insert dosing regimen is an anachronism.”

“[I]t is past time for the next chapter to be written with respect to antithrombotic adjuncts in PCI,” Sherwood and Tcheng wrote.

The authors of the paper and accompanying editorial agreed that it was unlikely that a randomized controlled trial would occur to assess this and other off-label dosing. More comparative research through similarly large registries, they noted, could give new life to this and other familiar drugs.