Barmer GEK's Pharmaceutical Report 2014 criticises new oral anticoagulants as sales grow exponentially in Germany

New oral anticoagulants come under the microscope in Barmer GEK's Pharmaceutical Report 2014

In the latest edition of the influential Pharmaceutical Report (Arzneimittelreport) of Barmer GEK, one of Germany's largest statutory health insurance (GKV) funds, for 2014, published at the end of May, a considerable amount of attention is paid to new oral anticoagulant medicines – specifically Xarelto (rivaroxaban; Bayer, Germany), Pradaxa (dabigatran etexilate; Boehringer Ingelheim, Germany), and Eliquis (apixaban; Pfizer, US) – as part of a wider consideration of the potential savings on pharmaceuticals that the GKV funds could make if less emphasis were placed on the prescription of new, innovative medicines (see Germany: 29 May 2014: German pharma industry criticises Barmer GEK's call for savings measures, as drug spending rises 9% y/y in Q1).

At the press conference for the release of the 2014 report, one of its authors, Professor Dr Gerd Glaeske, head of the health economics, health policy and outcome research department at the University of Bremen, stated – as reports Deutsche Apotheker Zeitung – that the safety profile and benefit-risk ratio of these drugs (referring specifically to Xarelto and Pradaxa) have not been conclusively demonstrated, concluding that they should only be used in the case of patients for whom a vitamin K-antagonist (VKA) such as phenoprocoumon or warfarin is not a treatment option. Furthermore, Glaeske has reportedly referred to the fact that Xarelto is discussed "in connection" with 133 deaths in 2013, stating that while a causal link between Xarelto and these deaths has not been confirmed, it is possible to speak of the new oral anticoagulants as "problematic" drugs. He is also reported as criticising the fact that no effective antidotes are available for these new drugs, in order to stop unwanted bleeding.

Bayer defends Xarelto

Deutsche Apothker Zeitung reports the response of Bayer stating that the conclusion that Xarelto should only be used in patients for whom warfarin or another VKA is not an option is "incomprehensible", pointing to what it describes as a "more predictable anticoagulation", in the case of which routine coagulation monitoring or regular adjustment of dosing is unnecessary. Furthermore, Bayer is reported as emphasising the lower risk of unwanted interactions with other medicines, insisting that VKAs do not have these advantages. In addition, the source also quotes the guidance from Germany's Federal Institute for Drugs and Medical Devices (BfArM) in 2013 that no new risk position was in place regarding the new oral anticoagulants, based on risk assessment at a European level, while citing BfArM's estimate that there were 102 reports of deaths of patients previously treated with Xarelto. However, the source has emphasised that no causal links between these deaths and Xarelto treatment could be established, pointing to the fact that there had been a significant increase in the number of prescriptions written for the drug in recent years.

Massive rise in sales of new oral anticoagulants in 2012–13

In the Barmer GEK Pharmaceutical Report 2014, which can be accessed in its entirety, here, in German, the development of the sales of the new oral anticoagulants can be seen over the last two years, compared with that of VKAs. As shown below, there has been a dramatic rise in the sales of the new oral drugs, with the sales of the longer-established Xarelto rising by as much as 205% year-on-year (y/y) in 2013, while the newest of the group, Eliquis, saw an increase of 5,017% y/y in sales last year.

Outlook and implications

Glaeske has called for the urgent preparation of a report regarding the risk-benefit ratio of the group of new oral anticoagulants, two of which – Xarelto and Pradaxa – were originally placed in the market before the Pharmaceutical Market Restructuring Act (AMNOG) came into force at the beginning of 2011 and have therefore not been put through the early benefit assessment process, although the G-BA identified them last year as drugs that should undergo a retroactive benefit assessment, before the retrospective benefit process was abandoned completely. This abandonment has been controversial, specifically for the GKV funds, which have seen it as a reason why medicines that have not been through a full benefit assessment under AMNOG continue to enjoy high sales – the funds consider these disproportionate to the drugs' actual benefits.

The fact that a report by a major GKV fund is questioning the considerable increase in the number of prescriptions written for these medicines, at a time when spending on pharmaceuticals by GKV funds is increasing significantly – 9% y/y in the first quarter of 2014 – is hardly a surprise. This is especially apposite considering the fact that the new oral anticoagulants have yet to establish themselves as the standard of care above warfarin in the prevention of venous thromboembolism in patients undergoing hip or knee surgery or in the prevention of stroke in atrial fibrillation patients, among the other approved indications of Xarelto and its competitor new oral anticoagulants.

The influential Barmer GEK report is likely to create the conditions for debate on this subject, which in turn has the potential to lead to new savings measures in the pharmaceutical sphere, which the report's authors and sponsors are so keen to see implemented.