Indirect Comparisons of the New Oral Anticoagulants in Patients with Non-Valvular Atrial Fibrillation

Abstract 4363

The efficacy and safety of new oral anticoagulants has been demonstrated for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) by dabigatran in the RE-LY trial (150mg and 110mg bid), rivaroxaban in the ROCKET AF trial (20mg od), and apixaban in the ARISTOTLE trial (5mg bid) versus INR-adjusted warfarin. Direct comparisons of the NOACs in this indication are unlikely to be performed.

A total of 4 indirect comparisons of these trials on the efficacy and safety of NOACs in patients with NVAF have now been published within only 3 months (Lip et al 2012, Harenberg et al 2012, Mantha et al 2012, Wells et al 2012). Here, we compare the results of these 4 network meta-analysis (NMA).

In all 4 NMAs of the 3 new oral anticoagulants dabigatran (150mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110mg bid, p<0.04) and rivaroxaban (p<0.04). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150mg bid, p<0.04) or rivaroxaban (p<0.005). Intracerebral haemorrhage occurred with equal frequency for all agents and regimens except for rivaroxaban (higher risk than dabigatran 110mg bid, p<0.005). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all p<0.05). All-cause mortality was not different for any agent or regimen. Some minor differences between the NMAs may result from the approved doses of dabigatran by the FDA (150mg bid and 75mg bid) and EMA (150mg bid and 110mg bid), as the inclusion of the 110 mg bid dose of dabigatran into the NMA may not be seen relevant in the US.

Based on this comparison, doctors and patients have to decide which suggestions of the 4 groups of authors seem more convincing: to change to or to start with one of the NOACs depending on the individual thrombotic or bleeding risk or to wait for the results from a large (and expensive) head-to-head randomised controlled trial which may take years to perform.