Amitava Banerjee, University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK, and co-authors have used “real world” data to show, in a study published in Thrombosis and Haemostasis, that three new oral anticoagulants have greater net clinical benefit than warfarin in patients with atrial fibrillation who have a high risk of stroke and bleeding.
Using data from the recent anticoagulant trials (eg, ARISTOTLE), Banerjee et al estimated the net clinical benefit (incidence of ischaemic stroke vs. the incidence of intracranial bleeding) of dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Bayer) and apixaban (Eliquis, Pfizer and Bristol-Myers Squibb) in patients with non-valvular atrial fibrillation. They then compared these figures with the net clinical benefit of not receiving any treatment and the net clinical benefit of receiving warfarin in patients with non-valvular atrial fibrillation using data from the Danish National Patient Registry.
Overall, the incidence of ischaemic stroke was lower in people receiving warfarin than in people not receiving any treatment (0.53 per 100 person years vs. 1 per 100 person years, respectively). However, compared with warfarin, the incidence of ischaemic stroke was lower for all of the oral anticoagulants with dabigatran 150mg having the lowest rate of ischaemic stroke (0.35 per 100 person years). Additionally, the numbers needed to treat (NNT) to prevent one ischaemic stroke a year were also lower for the new oral anticoagulants. Banerjee et al reported: “The NNT at CHADS2 score of ≥2 were 74 for warfarin, 66 for dabigatran 110mg, 52 for dabigatran 150mg, 60 for rivaroxaban (intention-to-treat analysis) and 59 for apixaban, respectively. The corresponding NNTs at CHA2DS2-VASc score of ≥2 were 109 for warfarin, 97 for dabigatran 110mg, 78 for dabigatran 150mg, 88 for rivaroxaban (intention-to-treat analysis), and 87 for apixaban, respectively.”
The incidence of intracranial haemorrhage was also lower in people receiving a new oral anticoagulant compared with people receiving warfarin, and again the lowest rate was seen in people receiving dabigatran (but with 110mg dose rather than the 150mg dose): 0.44 per 100 person years for warfarin vs. 0.14 per 100 person years for 110mg dabigatran.
Compared with people receiving no treatment, all of the new anticoagulants provided a net clinical benefit except in people with a CHADS2 score of 0 and a HAS-BLED score of >3. Warfarin only had a net clinical benefit (compared with no treatment) in people with a CHADS2 score of≥1 or a CHADS2DS2-VASc score of ≥2. Banerjee et al reported: “In patients with CHADS2 score of ≥1 or CHA2DS2DS2-VASc score of ≥2, the three new oral anticoagulants appear superior to warfarin for net clinical benefit, regardless of the risk of bleeding. When risk of bleeding and stroke are both high, all three drugs had a greater net clinical benefit than warfarin.”
Banerjee et al explained that a limitation of their study was that while the figures for people receiving warfarin or no treatment did reflect “real world” data because they were taken from the registry, the data for the novel oral anticoagulants did not (because they were from clinical trials). They wrote: “Therefore, modelling the net clinical benefit of the new oral anticoagulants on the basis of trial outcomes may not be the same as if derived from a ‘real world’ clinical registry of these drugs.” However they added in the absence of head-to-head trials for these new drugs, their analysis “may help inform decision-making processes when all these new oral anticoagulants become available for clinicians to prescribe for stroke prevention in atrial fibrillation.” Banerjee told Cardiac Rhythm News: “We need longer-term data regarding stroke and bleeding outcomes with the new agents in the ‘real-world’ setting, but at the moment, this type of modelling analysis is our best estimate, based on trial outcomes.”