Dabigatran tied to GI bleeding in elderly

Last Updated: 2015-06-05

By David Douglas

NEW YORK (Reuters Health) - In managing thrombotic risks in the elderly, new direct oral anticoagulants (DOACs) seem similar to vitamin K antagonists (VKAs) or offer greater benefits, but dabigatran may pose more risk of gastrointestinal bleeding, according to UK researchers.

In a systematic review and meta-analysis online May 20 in Circulation, Drs. Manuj Sharma and Mariam Molokhia of King's College, London, and colleagues sought to explore safety concerning bleeding risks (and benefits) of new DOACs with a particular focus on assessing risk in those aged over 75 years.

"This is the first study that has attained and assessed all available evidence for dabigatran, apixaban, rivaroxaban and edoxaban in atrial fibrillation (AF) and treatment of venous thromboembolism in the elderly from literature, regulatory bodies and drug manufacturers," Drs. Sharma and Molokhia told Reuters Health in a joint email.

The researchers ultimately examined data from these sources covering some 102,000 participants, more than 31,000 of whom were elderly.

Dabigatran, continued Drs. Sharma and Molokhia, "was associated with a higher risk of gastrointestinal bleeding than older drugs including warfarin. However there were lower risks of intracranial bleeding seen with dabigatran, apixaban and rivaroxaban. Insufficient data for apixaban, edoxaban and rivaroxaban indicates further work is needed to clarify their bleeding risks in the elderly."

Nevertheless, in the elderly, a significant reduction in risk of major bleeding compared to VKA was observed for apixaban (odds ratio, 0.63), edoxaban 60 mg (OR, 0.81) and 30 mg (OR, 0.46). Their superiority was also apparent in the total population.

Dabigatran 150 mg showed a non-significantly higher risk of major bleeding compared to VKA in the elderly (OR, 1.18). GI bleeding was significantly increased with both 150 mg (OR, 1.78) and 110 mg (OR, 1.40).

"The results have most significance for prescribers of DOACs in elderly populations who may be at a higher risk of bleeding due to pre-existing illnesses and other medications they may be on," said Drs. Sharma and Molokhia.

"In particular," they added, "our study suggests that caution is required in prescribing where there may be additional risk factors for gastrointestinal bleeding in the elderly, particularly with the anticoagulant dabigatran. Insufficient data for apixaban, edoxaban and rivaroxaban meant all bleeding risks, particularly gastrointestinal risks, could not be fully explored in the elderly."

The next step, they concluded, is "To clarify bleeding risks further, particularly gastrointestinal bleeding risks for apixaban, edoxaban and rivaroxaban in older populations (75+)."

Commenting on the findings by email, Dr. Kelvin Ng told Reuters Health that the study "supports the use of DOACS for stroke prevention in atrial fibrillation (SPAF) and treatment of acute venous thromboembolism (VTE) in patients 75 years and older."

Dr. Ng, an assistant professor in stroke medicine at McMaster University in Hamilton, Ontario, Canada, added that, "The efficacy of DOACS for SPAF and the treatment of VTE was preserved in the elderly with no significant disproportionate increased risk of bleeding. The pooled analysis supports the notion that patients should not be excluded from anticoagulation with DOACS on the basis of age alone. In fact, the Factor Xa inhibitors may be safer than VKA in the elderly and could be considered as the preferred choice for anticoagulation."

The study did not have commercial funding.

SOURCE: http://bit.ly/1EZJRLO

Circulation 2015.