The use of novel oral anticoagulants (NOACs) has increased rapidly in Ontario, Canada, especially in people aged 85 years and over, in the 2 years since the drugs were approved for use in patients with atrial fibrillation (AF), according to new research published in CMAJ Open. This rapid increase signals the need to evaluate outcomes from the use of these drugs in an elderly, high-risk population much older than the population involved in the studies.
More than 350 000 Canadians, especially older people, have AF, and anticoagulants are used for the prevention of stroke in these patients. Many seniors are hospitalized for adverse events from taking anticoagulants because of a higher risk of bleeding in older patients.
NOACs were approved for use in patients with AF in 2010, with dabigatran approved in October and rivaroxaban and apixaban in 2012. The Canadian Cardiovascular Society revised its guidelines to recommend these drugs as first-line therapy over warfarin to help prevent stroke.
"However, patients in real clinical settings often differ from participants of randomized trials used to inform the development of these guidelines," writes Yan Xu, Queen's University, Kingston, Ontario, with coauthors. "With respect to novel oral anticoagulants, age is of particular interest given the higher risk of bleeding among older patients and the lack of an antidote."
Researchers looked at data for Ontario residents over age 20 years who had filled prescriptions for anticoagulants from October 2010 and compared numbers per 100 000 people with results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.
They observed a 20-fold increase in the number of prescriptions for NOACs in Ontario, rising from 16 to 336 prescriptions per 100 000 people. Dabigatran was the most commonly prescribed drug, increasing from 3 to 274 prescriptions per 100,000 people. During the same period, prescriptions for the commonly used blood thinner warfarin decreased from 1526 to 1316 prescriptions per 100 000 people. Seniors aged 85 years and over had the highest number of prescriptions for dabigatran as did people aged 64 to 85 years old.
"Although results of the RELY-ABLE study, which looked at the long-term effects of dabigatran in patients completing the RE-LY trial, suggest long-term safety and efficacy of dabigatran in the phase IV trial setting, growth in the uptake of novel oral anticoagulants in very old patients, a group at high risk of bleeding, signals the need to evaluate outcomes in clinical practice to better guide the use of these agents," the authors conclude.
In a related commentary published in CMAJ, researchers write that the evidence supports the use of NOACs in older patients. Analyses of data on more than 19 000 patients over age 75 enrolled in randomized trials shows benefits of NOACs over warfarin.
"We believe that the findings by Xu and colleagues of increasing use of new oral anticoagulants among Canadians with atrial fibrillation are encouraging and that the pattern of uptake of these agents is supported by the data from the randomized trials," writes Dr. John Eikelboom, associate professor of medicine at McMaster University, and clinician with Hamilton Health Sciences, Hamilton, Ontario, with coauthors. "We agree, however, that there is no room for complacency because anticoagulants can cause serious bleeding and the risk of complications in increased when new oral anticoagulants are not used according to approved indications."
Physicians must be careful to prescribe NOACs for the right patient at the correct dosage and follow-up to ensure no adverse effects, conclude the commentary authors.