When apixaban is added to the current standard of care for acute coronary syndrome (ACS), including aspirin and clopidogrel, it did not show a statistically significant difference in ischemic events, according to a trial presented Tuesday at the European Society of Cardiology (ESC) congress in Munich, Germany.
Bristol-Myers Squibb (BMS) and Pfizer’s apixaban, designed to target the activity of Factor Xa, one of several enzymes involved in process of blood coagulation. Last week, BMS and Pfizer said that they are not going to seek FDA approval next year for apixaban, based on early evaluation results from a Phase III study, ADVANCE-1, which did not meet its primary endpoint, (i.e., non-inferiority to Sanofi-Aventis’ Lovenox (enoxaparin) for the prevention of venous thromboembolism).
The drug is just one of several new anti-clotting agents under development because physicians say they need safer, better anticoagulants. Millions of patients take anti-clotting drugs on a regular basis. Most are prescribed aspirin, clopidogrel (Pfizer’s Plavix) and/or warfarin, which is hard to properly and safely manage.
“One of the most vexing problems in cardiology is identifying the right combination of drugs that can inhibit clot formation but not increase the risk of serious bleeding," said study lead John Alexander, MD, a cardiologist at Duke University Medical Center in Durham, N.C., who presented the trial during the ESC’s late-breaking sessions.
Alexander and colleagues studied the use of apixaban in 1,715 patients from 14 countries throughout Europe and North America, who had suffered a recent heart attack. Roughly two-thirds of the patients had undergone angioplasty to clear blocked arteries and 99 percent of them were taking either aspirin, or aspirin and clopidogrel.
The study, APPRAISE, was designed to identify the optimal dose of apixaban, and participants were randomized into one of four doses of apixaban or a placebo. The researchers tracked the incidence of bleeding and recurrent heart attack, stroke, chest pain requiring hospitalization or additional procedures or death from cardiovascular problems for the following six months.
Researchers discovered a non-statistically significant trend suggesting that patients taking apixaban, along with their regular treatment, had a lower incidence of heart attack, stroke, chest pain or death from cardiovascular problems than patients taking a placebo.
However, bleeding was an issue, especially among those taking the higher doses of the drug (10 mg twice daily or 20 mg once daily), according to the presenters. Investigators discontinued those two arms of the study because patients were experiencing unacceptable rates of bleeding. Patients in the remaining arms of the study (2.5 mg twice daily or 10 mg once daily) also experienced more bleeding than those taking a placebo.
“The data show adding 5 or 10 milligrams of apixaban to a regimen of aspirin or aspirin and clopidogrel in patients hoping to prevent a second heart attack may offer therapeutic potential," Alexander said. "But this needs to be definitively demonstrated in a statistically significant manner in large, well-controlled studies.”