"There’s a lot of discussion in the clinical research community about the importance of these ultrasound-detected venous thromboses, whether they truly translate into something that may impact on a patient or they perhaps just go away on their own. Including them in a primary end point, as in the ADOPT study, is really questionable in my mind," he added.
"This is an important medical problem that needs to be adequately treated, and I don’t think we’re doing a good enough job now."
Dr. Mary Cushman said that going forward it will be critical to develop validated risk prediction models to identify the medical inpatients at highest risk for post-discharge VTE. That’s the right population to study in clinical trials.
The increased VTE risk in medically ill patients is known to extend for 3 months post discharge. An important question to address in future trials of the new oral factor Xa inhibitors is whether they should be utilized for that full 3-month risk period, rather than 1 month as in ADOPT, observed Dr. Cushman, professor of medicine and pathology at the University of Vermont, Burlington.
Dr. Goldhaber said he and his coinvestigators are now analyzing their nearly 7,000-patient database to identify key predictors of VTE for incorporation into a new risk prediction model.
Apixaban goes by the trade name of Eliquis in Europe, where the drug is approved for VTE prophylaxis in patients who have undergone total hip or knee replacement surgery. Eliquis is also the proposed trade name in the United States.
Apixaban in ADOPT failed to hit the home run it did earlier for stroke prevention in the setting of atrial fibrillation in the recently published, double-blind, randomized ARISTOTLE trial conducted in more than 18,000 patients. In ARISTOTLE, apixaban proved statistically significantly superior to warfarin in the key end points of prevention of stroke or systemic embolism, bleeding, and mortality (N. Engl. J. Med. 2011;365:981-92).
Simultaneous with Dr. Goldhaber’s presentation at the annual scientific sessions, ADOPT was published at http://www.nejm.org/doi/full/10.1056/nejmoa1110899 (doi:10.1056/NEJMoa1110899).
Dr. Goldhaber disclosed that he has served as a consultant to numerous pharmaceutical companies, including Bristol-Myers Squibb and Pfizer, which sponsored the ADOPT trial. Dr. Antman and Dr. Cushman declared having no relevant financial interests.