Direct oral anticoagulants (DOACs) have the same or less risk as warfarin for major bleeding or all-cause mortality when used to treat venous thromboembolism (VTE), according to a new study in The BMJ.
Warfarin has long been the principal drug available for the treatment of blood clots. But it has inherent limitations, such as a narrow therapeutic index and variability in patients’ responses, wrote lead researcher Min Jun, PhD, and investigators of the Canadian Network for Observational Drug Effect Studies (CNODES).
Newer DOACs, on the other hand, have relatively stable pharmacokinetics that don’t require regular monitoring and dose adjustment.
Recent randomized clinical trials have shown that DOACs are as effective as warfarin with a similar or reduced risk of major bleeding complications. But, the researchers pointed out, such clinical trials include a highly selected group of patients, so the rate of reported safety events such as major bleeding often doesn’t reflect those seen in routine clinical practice.
In the current study, researchers sought to better delineate the safety of DOACs—including dabigatran (Pradaxa®), apixaban (Eliquis®), and rivaroxaban (Xarelto®)—using real world, population-based data sources. They looked at health care data from the United States and five Canadian provinces to identify 59,525 adults (12,489 on a DOAC and 47,036 on warfarin) who were newly diagnosed with VTE and were prescribed a DOAC or warfarin within 30 days of diagnosis.
During an average follow-up of 85 days, 1,967 (3.3%) of the participants had major bleeding and 1,029 (1.7%) died.
The researchers found that the risk of major bleeding was similar for DOACs when compared with warfarin (pooled hazard ratio 0.92), with an association in favor of DOACs. The risk of death was no different between patients on DOACs and those on warfarin (pooled hazard ratio 0.99). The results remained unchanged after further analyses and with a longer follow-up period (180 days).
The researchers also found no evidence of heterogeneity across centers, between patients with and without chronic kidney disease, across age groups, or between male and female patients.
This study, the researchers concluded, suggests that DOAC use is not associated with higher major bleeding risk in VTE. In addition, the investigators conducted a series of sensitivity and subgroup analyses to ensure the robustness of the study findings and showed consistent results in different patient groups.
The authors acknowledged their study has limitations. For one, 95% of the patients prescribed a DOAC were on rivaroxaban. So, additional studies are needed to assess other DOACs, including apixaban and dabigatran, for treating VTE. Further studies are also needed to investigate the safety of DOACs over a longer term and among VTE patients with advanced chronic kidney disease, they added.
The Canadian Network for Observational Drug Effect Studies (CNODES) is funded by Canadian Institutes of Health Research (CIHR).