A Guide through Acronyms and Major Clinical Trials – 4th edition
Since the first discovery of heparin in 1916 by second year medical student Jay McLean and his Professor of Pharmacology, William Henry Howell, it took 20 years for the introduction of heparin to be used in clinical practice in 1936 and it's clinical use is still wide spread around the world. Since then it has taken decades for a further significant improvement of parenteral anticoagulants. As an example, the discovery of LMWH in 1976 and the first clinical trials during the early 1980s.
The discovery of dicoumarol as the cause of the "sweet clover disease", a hemorrhagic disease of cattle that have been fed with spoiled sweet clover, resulted in the description of the first oral anticoagulant in 1941 (Butt HR, Allen EU, Mayo Clin Proc 1941;16:388).
Despite the introduction of parenteral and oral anticoagulants in routine clinical practice, thromboembolic diseases remain a major cause of mortality and morbidity.
Currently four novel oral anticoagulants (OACs) are either launched or in phase III of clinical development to compete with vitamin K antagonists and parenteral anticoagulants:
- the direct oral thrombin inhibitor dabigatran
- the direct oral factor Xa inhibitors rivaroxaban, apixaban and edoxaban*
*edoxaban: in clinical development. No market authorization in Europe yet.
In addition, a parenteral direct factor Xa inhibitor, otamixaban is developed for acute coronary syndrome.
Around 200,000 patients were involved in dozens of phase III clinical trials with different novel OACs just within a few years. These studies resulted in a vast amount of new data and acronyms.
This guide is focused on providing summaries of phase III clinical trials (both completed and concurrent of the novel OACs) as well as offering an overview of the indications under investigation by the different drugs.
Where available, the phase II data of novel OACs in acute coronary syndrome and in atrial fibrillation, is included.
In addition, as a reminiscence to the plethora of clinical studies that have been conducted with other anticoagulants (i.e. vitamin K antagonists, unfractionated heparin and low molecular weight heparins), for each indication area covered in this book, a few selected examples of major or relevant trials with these drugs are summarized. Obviously the selection of these studies is far from being complete and can only be arbitrary.
Within the guide, antiplatelets are noted as active comparators to OACs, however this guide focuses specifically on OAC, and therefore antiplatelets are not referred to in any detail.
The trials are sorted alphabetically by their acronyms, where no acronyms are available, the name of the first author is referenced. All acronyms and first author names are supplemented by the year of the publication.