For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.
Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.
The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.
Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).
The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.
Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.
This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.
*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section.