February 10, 2015 | By Márcio Barra
INFARMED published in its news bulletin a study providing an overview of the consumption trends of anticoagulant therapy in Portugal, from 2010 to 2013. 1 The report shares some interesting numbers, especially when considering the new molecules that have been released during the timeframe, namely the new oral anticoagulants (NOACs). The full version is supposedly available in the regulators website, but unfortunately I was unable to find it.
In the last 5 years, the NOACS, of which there are the direct inhibitors of factors IIa (Dabigatran, commercial name Pradaxa) or factor Xa (Rivaroxaban, commercial name Xarelto, and Apixaban, commercial name Eliquis), have been granted European and US marketing authorization for the prevention of thrombotic events, such as stroke and systemic embolism, in high-risk adult patients. A third factor Xa inhibitor, Edoxaban (commercial name Savaysa) was recently approved in the USA by the FDA for the prevention of stroke and embolic events in patients with non-valvular atrial fibrillation. These drugs overcome some limitations associated with the traditional oral and parenteral anticoagulants, such as Warfarin and Low Molecular Weight Heparins, such as frequent monitoring of INR. As for efficacy, NOACs’ efficacy across a whole spectrum of prothrombotic conditions is, at least, non-inferior to the standard care. 2
Concerning safety, as any other new drug in the market, there are still unknowns associated with these drugs, alongside the fact that, unlike established agents such as Warfarin, at the moment there is no antidote available to reverse the anticoagulant effect. (Boehringer Ingelheim has an antidote currently in clinical development, idarucizumab. Initial Phase I study results appear promising. 3
Several studies have been published highlighting that these drugs are as safe as Warfarin, but these pool data from the pre-market, clinical trial phase. Until more real life data is available, intensive post-marketing intensive monitoring of the new anticoagulants is required. 4, 5, 6
The data used for INFARMEDs analysis concerns all reimbursed anticoagulant drugs, prescribed and dispensed to users of the Portuguese National Health Service (NHS). This includes Warfarin, Heparins, and the NOACs Dabigatran and Rivaroxaban. Apixaban has been reimbursed in 2014 and began commercialization in August of the same year, and as such it is not included in the analysis.
Sales data for NOACs begin in 2010, with the reimbursement approval of Dabigatran and Rivaroxaban. The initial therapeutic indication for Pradaxa was for the primary prevention of venous thromboembolism (VTE) in patients undergoing orthopedic surgery. Rivaroxaban was too initially approved for this indication.
In 2011, Dabigatran sales increased, owing to an additional indication approval – non valvular atrial fibrillation. The use of Warfarin also showed an upward trend over the period under review. An increase in the incidence of cardiovascular diseases was pointed as one potential reason.
Of interest is the expenses associated with the NOACs. The Portuguese National Health Service charges with the anticoagulant therapeutic subgroup increased from € 2.2 million in 2000, to € 26.9 million in 2013, of which € 16.8 million were with oral anticoagulants. Owing to the higher price of the NOACs compared to the more established treatments, in 2013 the costs for the use of Dabigatran – € 12.9 million – were approximately seven times higher than the cost of Warfarin – € 1.7 million, even though the latter enjoyed greater use. Dabigatran, at its highest price, costs around 78.24 € to 75.09 € for a 30 day course, while Warfarin barely reaches 5 €.
The higher cost of therapeutic innovations was recently pointed out by Eurico Castro Alves, president of INFARMED, as an uphill battle between regulators and the industry. In 2011, the expenses with therapeutic innovations in Portugal was € 56 million. This value shot up to € 142 million in 2014. 7
The report also shares some tidbits concerning prescription patterns of anticoagulant drugs. In the case of Dabigatran, the oral thrombin inhibitor was adopted in clinical practice more quickly by physicians in private care. At the end of 2013, Dabigatran accounted for almost 50% of anticoagulants prescribed in private care. This change in usage pattern was also observed by doctors in health centers, but to a less extent.
I am curious to see the full data contained by the report, and hope to see it available to the public soon.