New Blood Thinner Ends Trial With Mixed Results
November 18, 2009 — A new, reversible blood thinner did not prove superior over placebo for its primary endpoints of heart attack and need for revascularization, but it did reduce in-stent blood clots. Researchers reported the findings in a late-breaking clinical trial presentation at the American Heart Association’s Scientific Sessions this week.
CHAMPION PLATFORM, a phase III trial, included 5,362 angioplasty-plus-stent patients randomized to receive either a placebo or the investigational drug cangrelor during procedures to reopen coronary artery blockages. Cangrelor is a potent, fast-acting and reversible anti-clotting drug delivered intravenously.
After their procedures, all patients received 600 mg of the oral, nonreversible anti-platelet drug clopidogrel, which is routinely used in such procedures.
The trial, which enrolled patients beginning in 2006, ended when an interim review committee concluded that cangrelor would fail to show superiority over clopidogrel for its primary endpoint: a composite of all-cause death, heart attack and the need for coronary revascularization procedures.
“There was no statistically significant difference between the two arms of the trial at our 48-hour endpoint,” said Deepak L. Bhatt, M.D., MPH, chief of cardiology at the VA Boston Healthcare System. “However, a number of secondary endpoints had very interesting and informative findings. For instance, all-cause death as a stand-alone endpoint was reduced significantly from 0.7 percent in controls to 0.2 percent (67 percent reduction) in the cangrelor group.
“It is intriguing, of course, but it is a secondary endpoint and needs to be interpreted with some caution given that the primary endpoint was not met and the number of deaths overall was low,” he said.
Furthermore, acute stent thrombosis was significantly reduced in the test group.
“That’s something that interventional cardiologists really worry about, because stent thrombosis is often associated with a recurrent heart attack or death,” said Dr. Bhatt, who is also director of the integrated interventional cardiovascular program at Brigham and Women’s Hospital and the VA Boston Healthcare System, and a faculty member at Harvard Medical School in Boston. “Acute stent thrombosis was reduced from 0.6 percent in controls to 0.2 percent in the test group (69 percent reduction), again a significant benefit. So there seems to be a plausible mechanism by which mortality may have been reduced since stent thrombosis was reduced.”
Researchers found no difference in endpoints between test and control groups for severe bleeding and need for blood transfusion. However, less severe bleeding was significantly higher with the new agent, 5.4 percent vs. 3.4 percent in controls, an indication of the investigational drug’s potency, Dr. Bhatt said. Because it is reversible and is delivered through an intravenous line, bleeding events can be ended quickly after the drug is no longer administered.
Clopidogrel is given orally and is irreversible - once it binds to a platelet it remains for the life of that blood cell, usually seven to 10 days. That puts clopidogrel patients at higher risk of bleeding complications if they need emergency surgery, he said.
“At least in theory, cangrelor has all the attributes that an interventional cardiologist would want: Its onset of action is very quick and it’s very potent, but on the back end you can turn it off,” Dr. Bhatt said.
For more information: www.americanheart.org, www.themedicinescompany.com