TCT: HORIZONS still looks good for DES, Angiomax; trial ends at 3 years

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WASHINGTON, D.C.--The administration of bivalirudin (Angiomax, The Medicines Company) enhanced survival compared with the use of heparin plus a glycoprotein IIb/IIIa inhibitor in STEMI patients undergoing primary PCI after three years. HORIZONS-AMI, presented as a late-breaking trial at the annual Transcatheter Cardiovascular Therapeutics (TCT) conference, also found that the use of a paclitaxel-eluting stent was shown to be as safe and more effective than a bare-metal stent (BMS) at three years.

This is the final report from HORIZONS-AMI because of “administrative reasons,” reported co-principal investigator Gregg W. Stone, MD, director of cardiovascular research and the education center for interventional vascular therapy at New York-Presbyterian Hospital/Columbia Medical Center in New York City.

At one year, HORIZONS-AMI, which tracked 3,602 randomized STEMI patients, found that bivalirudin alone compared with heparin plus glycoprotein IIb/IIIa inhibitors resulted in comparable rates of MI and stent thrombosis, with significantly reduced rates of  major bleeding and mortality (all-cause and cardiac); and the Taxus paclitaxel-eluting stent (Boston Scientific) compared with Express BMS (Boston Scientific) reduced clinical and angiographic restenosis, with comparable rates of death, reinfarction and stent thrombosis.

In the pharmacology randomization arm, bivalirudin was found to have:

  • A significant 36 percent reduction in major bleeding and a significant 24 percent reduction in reinfarction, with non-significantly different rates of stent thrombosis, target vessel revascularization and stroke.
  • A significant 44 percent reduction in cardiac mortality and a 25 percent reduction in all-cause mortality, the latter representing 18 lives saved per 1,000 patients treated with bivalirudin (number needed to treat of 56 to save one life).

“Over time, the difference in reinfarction between bivalirudin and heparin plus glycoprotein IIb/IIIa inhibitors became positive,” Stone said. “There was a very weak, non-significant trend at one year, but at the end of the three years, there was a 1.8 percent absolute difference.”

Among patients with STEMI undergoing primary PCI at three years, the implantation of Taxus Express DES compared to Express BMS resulted in:

  • A significant 40 percent reduction in ischemic target lesion revascularization (TLR), with no evidence of late catch-up.
  • In patients without routine angiographic follow-up, the absolute reduction in TLR was 4 percent at three years (number needed to treat of 56 to save one life).
  • Non-significantly different rates of all-cause and cardiac mortality, reinfarction and stent thrombosis.

Stone noted that a subset of study participants had a marked increase in incidence rates after 13 months, when there was a planned, routine angiographic follow-up. “We had separated out the 12-month primary endpoint from routine angiographic follow-up, so it wouldn’t interfere with the primary 12-month endpoint, but there were a lot of additional revascularizations provoked at 13 months,” he said. “While the absolute hazard hasn’t changed, it did increase the relative benefit of paclitaxel-eluting stents, compared with BMS.”

Comparing the groups that had angiographic follow-up with the “artificial, study-induced increase in TLR,” Stone noted an increase compared with “smooth curves over time, showing a statistically significant 33 percent relative reduction, or 4 percent absolute reduction in TLR of Taxus compared with BMS.”

Co-Principal Investigator Roxana Mehran, MD, director of cardiovascular research and interventional clinical trials at Mount Sinai in New York City, suggested that mortality curves continue to separate because of a lack of medicine adherence to dual-antiplatelet therapy, beta-blockers and statins, after a patient bleeds. “For whatever reason, the standard practice for a bleeding patient is not cared with the same standards,” she notes.

However, Stone noted that the dual-antiplatelet therapy was approximately the same in the overall population, so the overall mortality rate cannot be explained with the use of aspirin and clopidogrel use.” However, he acknowledged that based on the HORIZONS results and follow-up data, “patients that bleed tend to stop dual-antiplatelet therapy and statins, and some of that may contribute to the difference in late outcomes.”