Are Novel Oral Anticoagulants (Noacs) as Safe as They are Said to Be

Abstract

The main advantages of NOACs over warfarin are their predictable pharmacokinetics and clinical response thus obviating the need for routine anticoagulation monitoring or monitoring of plasma drug levels, fewer drug interactions and the lack of interaction with diet. More crucially NOACS were developed and marketed to be used as fixed-dose regimens, which is considered to be a substantial advantage over warfarin. Prescription numbers for NOACs have risen sharply since their launch for both newly diagnosed patients requiring initiation of anticoagulant therapy and existing patients on warfarin with poor anticoagulation control being switched to a NOAC, with prescriptions in England for dabigatran in 2012 compared to 2011 increasing 1,600%, from around 3,000 to around 48,000, and prescriptions for rivaroxaban in 2012 being around 16,000 [2]. Whilst non-inferiority of NOACs to warfarin in their clinical effectiveness for stroke prophylaxis in patients with atrial fibrillation in the RE-LY, ROCKET-AF, and ARISTOTLE studies has been established, the bleeding adverse reactions reported in those trials, may be contributed to by patient age, with the noted incidence of bleeding being greater in those aged 75 years and over [3-5]. It is of concern that in view of the use of NOACs in atrial fibrillation the more elderly were not well represented in the trials, and clinical experience is too short to provide models of use which optimise the benefits of therapy and ensure therapy can be safely prescribed. Although prescribing rates for NOACs have grown rapidly since their launch, concerns about fatal bleeds have emerged particularly in elderly people, who are at a greater risk. A later sub-analysis of the RE-LY trial data by the manufacturer of dabigatran, Boehringer Ingleheim, showed that there were 5-fold variations in plasma dabigatran concentration for each of the two doses (110 and 150 mg) that were tested [6]. Further analysis of the data showed that renal function is the most important determinant for