NOACs compare favourably to warfarin in new studies
June 22 2016
Two BMJ studies have further supported the use of alternatives to warfarin for anticoagulation needs in atrial fibrillation.
Overall, novel oral anticoagulants (NOACs) are not significantly different to warfarin in terms of risk of ischaemic stroke, but rivaroxaban was associated with a lower risk of ischaemic stroke or systemic embolism compared to warfarin, although with comparable major bleeding rates.
Meanwhile, “dabigatran and apixaban had non-significant hazard ratios compared with warfarin for ischaemic stroke or systemic embolism, whereas major bleeding rates were significantly lower with reference to warfarin.”
A study on the effects of polypharmacy in atrial fibrillation found that “apixaban was more effective than warfarin regardless of the number of concomitant drugs used.” Apibaxan also had lower bleeding rates compared to warfarin, although the researchers concluded that the size of benefit appeared to decrease as the number of concomitant medicines the patient was taking increased.
The studies, one based at Aalborg University, Denmark, and the other based at a number of centres around the world, had been assessing risks associated with NOACs.
The Danish study looked at the effectiveness and safety of the NOAC non-vitamin K antagonist oral anticoagulants dabigatran, rivaroxaban, and apixaban in comparison with warfarin in patients with atrial fibrillation who had not been given an anticoagulant previously. Outcomes were measured by ischaemic stroke, systemic embolism as well as bleeding.
Data from over 61,000 patients with non-valvular atrial fibrillation was analysed. NOACs were not significantly different to warfarin when the analysis was restricted to ischaemic stroke. However, “during one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99).”
The annual hazard ratios for dabigatran was 2.8% and for apixaban was 4.9%, although this was non-significant compared to warfarin. “The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%).”
The researchers concluded: “All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting.” While there were no significant differences between NOACs and warfarin for ischaemic stroke, “the risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.”
The second study looking at polypharmacy was part of the ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) trial. The multicentre study ran for five years from 2006 to 2011 and included 18,201 patients who either received apixaban 5mg twice daily or took warfarin with a target INR of 2.0 to 3.0.
Patients were also assessed for other treatment being used, and the median of taking six medicines was seen in almost 14,000 patients. Co-morbidities increased with increasing number of medicines taken, “as did the proportions of patients treated with drugs that interact with warfarin or apixaban.
“Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively).”
The researchers found a consistent relative risk reduction in stroke or systemic embolism for apibaxan compared to warfarin, regardless of the number of drugs being taken. There was also a small but significant reduction in major bleeding.
“In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe,” concluded the researchers.
TB Larsen et al. ‘Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study’. BMJ 2016;353:i3189.