ORLANDO, FLA — Treatment with one month of an investigational blood-thinning pill was no more effective than a shorter course of standard injected medicine at preventing dangerous blood clots in acutely ill patients, according to late-breaking research presented at the American Heart Association’s Scientific Sessions 2011.
However, the researchers said their study didn’t have the statistical power to make firm conclusions about the 30-day treatment.
The study is simultaneously published in the New England Journal of Medicine.
In the Apixaban Dosing to Optimize Protection from Thrombosis (ADOPT) Trial, researchers tested whether 30 days of oral apixaban would be safe and more effective than six to 14 days of injected enoxaparin in preventing blood clots known as venous thromboembolism (VTE).
The trial included more than 6,500 patients hospitalized for congestive heart failure, acute respiratory failure or other conditions that increase risk of VTE. All patients were 40 or older, had restricted mobility and were expected to be hospitalized at least three days. The trial was conducted at 302 medical centers in 35 countries.
Patients were randomly chosen to receive twice-daily 2.5 mg apixaban pills for 30 days or daily 40 mg shots of enoxaparin for six to 14 days.
Among the 4,695 patients for whom effectiveness data could be evaluated, 2.7 percent of those given apixaban for 30 days had a VTE event (death, deep vein thrombosis or pulmonary embolism), compared to a rate of 3.1 percent among patients given enoxaparin for six to 14 days during hospitalization. That difference was not statistically significant.
VTE affects about one in 1,000 Americans each year. It includes deep vein thrombosis, which arises in veins deep in the body or limbs (mostly the legs) and a potentially lethal complication known as pulmonary embolism, which can occur when a clot breaks free and blocks one or more arteries in the lungs.
“ADOPT may not be applicable to typical populations of hospitalized medically ill patients because routine screening for VTE is not ordinarily undertaken at the time of hospital discharge,” said Samuel Z. Goldhaber, M.D., lead researcher of the study and director of the Venous Thromboembolism Research Group at Brigham and Women’s Hospital in Boston, Mass.
Considering longer-term preventive treatment beyond hospital discharge is important for patients at risk for VTE, researchers said.
“Risk factors for VTE may actually increase after hospital discharge as patients may become more immobile when they are no longer prodded and encouraged to mobilize by hospital nurses and therapists,” Goldhaber said.
Researchers did not assess mobility after discharge in this study.
The researchers measured bleeding rates in the entire 6,528-patient study population to assess the treatment’s safety. Rates of total bleeding events were not significantly different between the two groups: 7.73 percent for apixaban and 6.81 percent for enoxaparin. Rates of “major” bleeding ― which causes death, stroke or other serious events ― were statistically higher (P=0.04) with apixaban (0.47 percent) compared to enoxaparin (0.19 percent).
Enoxaparin’s current recommended use is for six to 14 days, but many patients in real-world hospital settings receive a shorter course because the treatment is discontinued when their hospitalization ends; thus, conclusions about the drug comparison should be withheld, Goldhaber said.
Furthermore, differences between apixaban and enoxaparin begin to separate well after the final dose of enoxaparin, suggesting there might have been a more positive study outcome if researchers had extended apixaban for more than 30 days.
“It’s clear that the risk of VTE increases beyond the time of hospital discharge,” Goldhaber said. “The uncertain fate of the discharged patient susceptible to dangerous clotting remains one of the last frontiers where we struggle to find effective and safe VTE prevention.”
Co-authors are Alain Leizorovicz, M.D.; Ajay K. Kakkar, M.D., Ph.D.; Sylvia K. Haas, M.D., Ph.D.; Geno Merli, M.D.; Robert M. Knabb; Ph.D.; and Jeffrey I. Weitz, M.D.
Disclosures are here: http://newsroom.heart.org/pr/aha/document/Disclosures_for_LBCT.xlsx.
Bristol-Myers Squibb and Pfizer sponsored the study.
Statements and conclusions of study authors published in American Heart Association scientific meetings or presentations are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding .
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