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Direct oral anticoagulants as safe as warfarin after VTE

Major bleeding or death no more likely with DOACs than with warfarin in first 90 days’ treatment

Louise Prime

Wednesday, 18 October 2017

There is no higher risk of bleeding with direct oral anticoagulants (DOACs) than there is with warfarin for people taking the drugs following venous thromboembolism (VTE), an international team of researchers have shown. Nor were DOACs associated with a relatively higher risk of death.

The researchers behind this study*, published today in the BMJ, pointed out that warfarin has a narrow therapeutic index and patients’ responses to it show variability dependent on a range of factors including diet and concomitant drugs – so DOACs, which have relatively stable pharmacokinetics, are increasingly used in clinical practice following VTE to avoid the need for regular monitoring. However, they said that although clinical trials have shown DOACs to be similarly effective to warfarin, with no higher risk of major bleeding, these trials have included a highly selected patient group. So, they wanted to assess safety and effectiveness among a more typical patient group.

They accessed healthcare data from six jurisdictions of Canada and the United States, from which they identified 59,525 people who had a new diagnosis of VTE and who had been prescribed a DOAC (12,489 patients) or warfarin (47,036 patients) within 30 days of diagnosis. Any hospital admissions or emergency department visits for major bleeding among these patients, and deaths from all causes, were recorded if they occurred within 90 days of starting treatment.

During a mean follow up of 85 days, 1,967 (3.3%) of participants had a major bleed; and 1,029 (1.7%) died. The researchers calculated that, after taking into account factors that could lead to bias (such as demographic factors, comorbidities, and history of major bleeding), the risk of major bleeding was similar for DOACs compared with warfarin use “with the overall direction of the association favouring DOAC use”.

Bleeding rates at 30 days ranged between 0.2% and 2.9% for DOACs and 0.2% and 2.9% for warfarin. Bleeding rates at 60 days ranged between 0.4% and 4.3% for DOACs and 0.4% and 4.3% for warfarin. They also reported no difference in the risk of death for people taking DOACs compared with those using warfarin. When they conducted further analyses, including using a 180-day follow-up period, their results were unchanged.

The researchers pointed out that their study cannot show causation as it was observational and they could not rule out other potential confounding factors; in addition, they did not consider other factors such as longer-term aspects of DOACs or their safety among people with chronic kidney disease.

Nevertheless, they concluded: “In this analysis of data from large cohorts of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with  an increased risk of major bleeding or all-cause mortality in the first 90 days of treatment. These results were consistent for patients with and without chronic kidney disease, across all age groups, and for men and women.”

* Jun M, Lix LM, Durand M, et al. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study. BMJ 2017; 359: j4323. doi: 10.1136/bmj.j4323

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