text: Researchers at Boehringer Ingelheim also used the publicized information about the NAPAP-fIIa crystal structure, starting with the NAPAP structure that led to the discovery of dabigatran, which is a very polar compound and therefore not orally active.  By masking the amidinium moiety as a carbamate-ester and turning the carboxylate into an ester they were able to make a prodrug called dabigatran etexilate, a highly lipophilic, gastrointestinally absorbed and orally bioavailable double prodrug such as ximelagatran, with the plasma half-life of approximately 12 hours. Dabigatran etexilate is rapidly absorbed, it lacks interaction with cytochrome P450 enzymes and with other food and drugs, there is no need for routine monitoring and it has a broad therapeutic index and a fixed-dose administration, which is excellent safety compared with warfarin. Unlike ximelagatran, a long-term treatment of dabigatran etexilate has not been linked with hepatic toxicity, seeing as how the drug is predominantly eliminated (>80%) by the kidneys. Dabigatran etexilate was approved in Canada and Europe in 2008 for the prevention of VTE in patients undergoing hip- and knee surgery. In October 2010 the US FDA approved dabigatran etexilate for the prevention of stroke in patients with atrial fibrillation (AF). Many pharmaceutical companies have attempted to develop orally bioavailable DTI drugs but dabigatran etexilate is the only one to reach the market.
  In a 2012 meta-analysis dabigatran was associated with increased risk of myocardial infarction (MI) or ACS when tested against different controls in a broad spectrum of patients.