“This is an interesting idea, with potentially interesting results, but at the moment, it is only valuable for generation of hypotheses regarding future regimens of thrombolysis,” Konstantinides said.
He said he looks forward to seeing the full results of MOPETT published in a peer-reviewed journal.
Konstantinides’ research group is studying the same topic in the Pulmonary Embolism Thrombolysis (PEITHO) study, which includes 1,000 normotensive patients with PE who are randomly assigned to thrombolysis vs. placebo. Data should be available by the end of this year.
“Maybe then we will know more on the subject,” Konstantinides said. – by Rob Volansky
Büller H. Late-breaking clinical trials III. Presented at: the American College of Cardiology 61st Scientific Sessions & Expo; March 24-27, 2012; Chicago.
CDC. Deep Vein Thrombosis/Pulmonary Embolism Data & Statistics. Available at: www.cdc.gov/ncbddd/dvt/data.html. Accessed Oct. 17, 2012.
EINSTEIN-PE investigators. N Engl J Med. 2012;366:1287-1297.
Guyatt GH. Chest. 2012;141(2 Suppl):7S-47S.
Patient Information Guide: Deep Vein Thrombosis and Pulmonary Embolism. 2012. Clot Connect patient education program. University of North Carolina Hemophilia and Thrombosis Center. Available at: http://files.www.clotconnect.org/DVT_and_PE.pdf. Accessed Oct. 18, 2012.
Sharifi M. Joint ACC/Journal of the American Medical Association late-breaking clinical trials. Presented at: the American College of Cardiology 61st Scientific Sessions & Expo; March 24-27, 2012; Chicago.
For more information:
Charles Abrams, MD, may be reached at 912 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104; email: firstname.lastname@example.org.
Harry R. Büller, MD, PhD, may be reached at Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam; email: email@example.com.
Samuel Z. Goldhaber, MD, may be reached at Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115; email: firstname.lastname@example.org.
Menno Huisman, MD, PhD, may be reached at Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Building 1, P.O. Box 9600, 2300 RC Leiden, the Netherlands; email: email@example.com.
Stavros V. Konstantinides, MD, FESC, may be reached at Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrabe 1, 55131 Mainz; email: firstname.lastname@example.org.
Stephan Moll, MD, may be reached at UNC Hemophilia and Thrombosis Center, 170 Manning Drive, 3rd Floor Physicians Office Building, Campus Box 7016, Chapel Hill, NC 27599-7016; email: email@example.com.
Mohsen Sharifi, MD, may be reached at Arizona Cardiovascular Consultants, 5440 E. Southern Ave. #104, Mesa, AZ 85206.
Disclosures: Abrams, Huisman and Konstantinides report no relevant financial disclosures. Büller reports research support, consulting work and advisory board roles with Bayer HealthCare, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Isis, Pfizer, Roche, Sanofi-Aventis and Thrombogenics. Goldhaber serves as a consultant for Janssen, and his research group receives support from Johnson & Johnson. Moll reports consulting with Bayer, Boehringer-Ingelheim, Daiichi and Johnson & Johnson. Sharifi reports consulting with Covidien.
The potential is there.
Rivaroxaban (Xarelto, Janssen) and dabigatran (Pradaxa, Boehringer Ingelheim) have the potential to change the paradigm in thrombosis. The EINSTEIN trials were convincing and well done. They were carefully controlled clinical trials, but accrual was limited to patients who were not at high risk of bleeding complications. This led to a low incidence of bleeding during the trials, which was comparable to that seen with warfarin (Coumadin, Bristol-Myers Squibb). Whether the same low risk will be observed in the community without strict selection guidelines of a clinical trial is unknown.
There is no easy way to reverse bleeding due to the new oral anticoagulants. With warfarin, plasma can be used to reverse bleeding relatively quickly. Plasma does not reliably reverse bleeding caused by the newer oral anticoagulant drugs. Similar concerns apply to other agents, such as recombinant Factor VIIa or vitamin K complex concentrates, particularly the three factor concentrates currently available in the United States.
Speaking specifically of cancer, the same concerns apply.
Having said that, I do think these drugs have the potential to change the paradigm, but much more needs to be done to establish safety. An FDA press release suggests that bleeding risks associated with dabigatran do not appear to be greater than those expected from Coumadin, but most of this data applies to patients with atrial fibrillation. Whether this will apply to patients with venous or arterial thrombosis, particularly those with cancer, is uncertain.
We need studies specifically targeted toward patients with malignancies. There were not enough patients with cancer in the EINSTEIN studies to draw firm conclusions, and I presume they were probably not patients with advanced malignancies. We need specific studies looking at patients with all different types of neoplasms to determine the safety and efficacy profile of these drugs in patients with cancer.
Keith McCrae, MD, is a member of the staff in hematologic oncology and blood disorders at Cleveland Clinic’s Taussig Cancer Institute. He may be reached at Department of Cellular and Molecular Medicine (NC10), Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195; email: firstname.lastname@example.org. Disclosure: McCrae reports no relevant financial disclosures.
There are insufficient data to make a determination at this time.
Geno J. Merli
The EINSTEIN trials enrolled a large population of patients with venous thromboembolism. They demonstrated the efficacy and safety of rivaroxaban vs. low-molecular– weight heparin bridged to warfarin therapy.
Unfortunately, this important breakthrough in care really cannot yet be correlated to the cancer patient population with venous thromboembolism. The reason is that the cancer population enrolled was very small in both trials. In addition, rivaroxaban is an oral agent which — in a cancer population receiving chemotherapy — may become problematic with the nausea and vomiting associated with treatment.
Another concern for this population would be the non-reversibility of rivaroxaban should major bleeding develop during treatment.
I do believe that rivaroxaban is worth studying in patients with cancer and thrombosis. I am sure clinical trials will be developed to study this question in such a high-risk population.
Geno J. Merli, MD, is co-director of the Jefferson Vascular Center and clinical professor at Jefferson University Hospitals. He may be reached at Gibbon Building, Suite 6270, 111 S. 11th St., Philadelphia, PA 19107; email: email@example.com. Disclosure: Merli reports no relevant financial disclosures.