TCT.14: Heparin may come back in vogue, but in low doses

WASHINGTON, D.C.—Heparin is making a comeback in a big way, according to one statement made Sept. 14 at the Transcatheter Cardiovascular Therapeutics (TCT) conference. The speaker went on to say that it will become the anticoagulant of choice over bivalirudin and others.

This position statement was part of the Cath Lab Directors’ Lunch. According to speaker Michael S. Lee, MD, of the University of California, Los Angeles Medical Center, heparin’s cost and safety at low doses will be the key to its success in the near future. Bivalirudin (The Medicines Company) may be the most frequently used agent in the U.S. right now; however, after nine years of experience working with both it and heparin, Lee stands behind heparin.

“If you think about this era of cost containment, we’ve got to look for different ways to treat patients safely but also under cost constraints,” Lee said.

Studies over time have shown that when compared to low-dose heparin and a pretreatment of thienopyridine or clopidogrel (Plavix, Bristol Myers-Squibb/Sonafi Aventis), bivalirudin alone had worse outcomes in some areas. While bleeding was still more frequent with the use of heparin, poorer ischemic rates were seen in patients given bivalirudin in the ACUITY trial, Lee noted. The HEAT PPI trial experienced a greater major adverse cardiovascular event (MACE) rate for patients taking bivalirudin and reinfarctions happened two times as often for bivalirudin patients.

Following similar low-dose studies, Lee and colleagues looked at providing low-risk patients with 40 units per kg and found “our bleeding rates were pretty low.” There was one cardiac death, eight MIs and no thrombosis reported.

The take home, Lee said, was that the increased risk of bleeding was with higher doses of heparin.

These and other trials have shown both to be as relatively safe and effective, but the biggest difference, according to Lee, is cost. As heparin is generic, its cost is lower and is relatively easy to obtain. Despite its mechanistic problems, Lee stated as long as it is properly dosed, it provides relief to patients at a fraction of the cost.

“It seems like back to the future. We’re talking a lot about anti-trauma therapy, which was the topic of this meeting [many] years ago,” stated discussant Sunil V. Rao, MD, of Duke University Medical Center in Durham, N.C., who then asked if there was a dose that could be considered too low in light of an unfractionated heparin study that had an increase in patients on the low-dose experiencing thrombosis.

Lee responded that there were no current guidelines to assist clinicians in knowing what dose was low enough to maintain efficacy and provide best benefit. “It’s a fine line,” Lee admitted. Current guidelines suggest between 70 and 100 units per kg, but no more along with P2Y12 inhibitors and selective use of GP IIb/IIIa inhibitors. However, safety and efficacy were shown at much lower doses.

Discussant Kirk N. Garratt, MD, of Lenox Hill Hospital in New York, added that part of the success of low-dose heparin is the use of modern antiplatelet therapies. Garratt warned, however, that some trial efficacy is misleading, based on work on healthy or relatively healthy patients. “A patient coming in with an infarct doesn’t absorb anywhere near the same way as a healthy volunteer,” Garratt said.

In those cases, when a clinician is looking to get a good door-to-balloon time, “don’t expect prasugrel to save the day,” Garratt warned.

Other studies have found that there are signals for mortality in bivalirudin use, independent of bleeding. As there is still more data in favor of bivalirudin, Garratt concluded, “If this weren’t a financial issue, we wouldn’t be having this conversation.”

Still, Garratt and others agreed that in a time when hospitals are looking to cut expenses, it’s hard to make an argument against using a drug if it is as safe at only a fraction of the cost.