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Target-specific oral anticoagulants reduced risk for bleeding in VTE, atrial fibrillation

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September 30, 2014

Target-specific oral anticoagulants reduced the risk for major, fatal and intracranial bleeding compared with vitamin K antagonists in patients with venous thromboembolism or atrial fibrillation, according to results of a meta-analysis.

Results also showed target-specific oral anticoagulants did not increase the risk for gastrointestinal bleeding.

Chatree Chai-Adisaksopha, MD, of the department of medicine at McMaster University in Hamilton, Canada, and colleagues identified 12 randomized controlled phase 3 trials comprised of 102,607 patients. Seven of the trials evaluated anticoagulation for venous thromboembolism (VTE), and five indicated anticoagulation for the prevention of stroke and systemic embolism from atrial fibrillation.

Anticoagulants assessed in the 12 trials included dabigatran (Pradaxa, Boehringer Ingelheim; n=4), rivaroxaban (Xarelto, Janssen; n=4), apixaban (Eliquis; Bristol-Myers Squibb, Pfizer; n=2) and edoxaban (Lixiana, Daiichi-Sankyo; n=2).

In total, 57,850 patients received target-specific oral anticoagulants, and 44,757 received vitamin K antagonists. The median treatment duration ranged from 1.6 to 2 years in the atrial fibrillation trials, and from 3 to 12 months in the VTE trials.

Patients who received target-specific oral anticoagulants experienced a reduced risk for overall major bleeding (RR=0.72; 95% CI, 0.62-0.85), fatal bleeding (RR=0.53; 95% CI, 0.43-0.64) and intracranial bleeding (RR=0.43; 95% CI, 0.37-0.5) compared with patients who received vitamin K antagonists.

Clinically relevant non-major bleeding (RR=0.78; 95 %CI, 0.68-0.9) and total bleeding (RR=0.76; 95% CI, 0.71-0.82) also were reduced with target-specific oral anticoagulants.

Researchers noted target-specific oral anticoagulants were associated with a similar risk for gastrointestinal bleeding as vitamin K antagonists (RR=0.94; 95% CI,

“When compared to vitamin K antagonists administered to a target international normalized ratio [INR] of 2.0 to 3.0, target-specific oral anticoagulants are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant non-major bleeding and total bleeding,” Chai-Adisaksopha and colleagues concluded. “Additionally, target-specific oral anticoagulants do not appear to increase the risk of gastrointestinal hemorrhage.”

Disclosure: One researcher reports advisory board roles with and funding from AKP America, Bayer, Celgene, CSL Behring, Janssen, Leo Pharma, Portola and Shire.

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George M. Rodgers III

George M. Rodgers III

Since completion of the clinical trials of new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE), meta-analyses have been published on the aggregate data for each indication. The major focus of interest has been bleeding risk, in part, because the new drugs cannot be easily monitored, and there is no reversal agent yet available. The study by Chai-Adisaksopha and colleagues is noteworthy because it evaluates the combined trial database for both AF and VTE indications. The conclusions on safety are reassuring and indicate that the NOACs have superior safety vs. vitamin K antagonists across all bleeding subgroups (major bleeding, fatal bleeding, intracranial bleeding and gastrointestinal bleeding). Some might argue that data from clinical trials may not be extrapolated to results from community practice, where bleeding risks may be greater. However, it appears that community trial data also is reassuring — at least with regard to one of the new drugs, rivaroxaban (Xarelto, Janssen). Results of the Dresden rivaroxaban registry confirm the clinical trials’ safety advantages of NOACs in routine clinical practice. (Beyer-Westendorf J. Blood. 2014;124:955-962). The preponderance of the available data supports preferential use of NOAC therapy, excluding patients with cancer or significant renal impairment.

George M. Rodgers III, MD, PhD
University of Utah School of Medicine

Disclosure: Rodgers reports no relevant financial disclosures.