Wednesday, June 25, 2008

Trial indicates new anticoagulant and antidote could be safe, fast option for patients
by Kelly Winget

Anti-blood clotting drugs are routinely used to treat and prevent acute blood clots from forming in veins and arteries during angioplasty or coronary artery bypass surgery, but a percent of patients will still experience major hemorrhages. A recent Phase 1b trial, led by DCRI researchers, found a new anticoagulant and its antidote could offer a safe way to quickly reverse the effects of the anticoagulant.

The results of the study were published in the June 3 issue of Circulation. The DCRI organized the study and performed all data management and statistical analyses.

The trial was the first to show an RNA aptamer drug and antidote, known as REG1, which could limit and then restore the activity of factor IXa, which helps control blood clotting, specifically for patients with stable coronary artery disease.

Researchers were testing REG1 for safety and for how well patients who were at increased risk for having a cardiovascular event would tolerate the drug. It consists of an injectable anti-blood clotting drug that limits factor IXa and the injectable antidote.

Although angioplasty and coronary artery bypass surgeries are effective for restoring blood flow to the heart, major hemorrhages will occur in approximately 5 percent of patients who have an angioplasty and up to 5 percent of patients who have bypass surgery need a second operation to control bleeding. Hemorrhages can significantly increase the risk of death and are associated with higher hospitalization costs.

Patients who require procedures to widen arteries and restore blood flow to the heart are often older, typically take other medications that can affect blood flow and are at a greater risk for bleeding. For optimal care, these patients in particular need safe, fast-acting anticoagulants, which can quickly be reversed.

Fifty patients were enrolled in the trial, and they were between the ages of 50 and 75, had stable coronary artery disease and were either taking aspirin, clopidogrel or both for more than a week before the start of the trial.

Researchers found that patients responded well to both the anticoagulant and the antidote, with no major bleeding or adverse events observed in the seven days of follow-up. There were five patients who had minor bleeding and blood clots at the intravenous site.

Most antidotes to anti-blood clotting drugs that are used today are unpredictable and tend to have adverse side effects. Researchers did not find any serious allergic reactions or blood disturbances for the antidote portion of REG1. REG1 will next go through a Phase 2 trial with patients undergoing angioplasty.

DCRI researchers who participated in the trial include Mark Chan, MD, MHS; Shelley Myles, BSPH, RN; Laura Aberle, MS; Min Lin, PhD; Chiara Melloni, MD, MHS; John Alexander, MD, MHS; Robert Harrington, MD, and Richard Becker, MD.