WCM-Q Grand Rounds discusses new anticoagulation drugs

Recent advances in anticoagulation therapies were explained in the latest instalment of Weill Cornell Medicine-Qatar’s (WCM-Q) series of Grand Rounds lectures.

Dr. Liam Fernyhough, Assistant Professor of Medicine at WCM-Q, gave a brief history of the evolution of anticoagulation medications, which are used to prevent blood clots forming in at-risk patients, thereby reducing the likelihood of life-threatening conditions such as strokes and heart attacks.

Dr. Fernyhough explained that the first anticoagulants were developed in the US in the 1930s after outbreaks of fatal hemorrhagic disease among cattle were found to be caused by the animals being fed moldy hay. Researchers analyzed the mold and isolated a compound called dicoumarol, which they found to be a powerful anticoagulant. This was developed into a rat poison called Warfarin that was later found to be a safe and effective therapeutic anticoagulant for humans use. However, Warfarin has a number of drawbacks, as the dosage differs significantly between patients, it requires laboratory monitoring of the patient, it has many interactions with other drugs, and it is affected by diet as foods high in Vitamin K diminish its effects.

Dr. Fernyhough, who is also Senior Consultant in Hematology at the National Center for Cancer Care and Research at Hamad Medical Corporation, said: “These issues are all problematic, but the number one problem with Warfarin is that it causes bleeding. If we could develop a drug that had the anticoagulant properties of Warfarin but did not cause bleeding, had fewer interactions with other drugs, was not affected by diet, and could be given as a fixed dose, that would be highly beneficial for patients.”

He then explained that four effective Warfarin alternatives – Dabigatran, Rivaroxaban, Apixaban, Edoxaban – all require differential dosage depending on a number of variables. These drugs also have the problem that they have interactions with many other drugs. While Apixaban and Edoxaban cause slightly less bleeding than Warfarin, Dabigatran and Rivaroxaban cause about the same amount. 

Dr. Fernyhough said: “Sadly, there is still significant severe bleeding which is encountered in a small number of patients on these agents. So, we cannot say there is no bleeding but at least it is the same or slightly less than Warfarin. They are not the wonder-drugs that we hoped for, but they certainly have a number of good features. Many clinicians prefer to continue using Warfarin, because it still has many benefits in selected stable patients. However, when you do a meta-analysis of these newer therapies, specifically relating to atrial fibrillation (abnormal heart rhythm), all-cause mortality is decreased as compared to Warfarin. This is really powerful information. It is thought that this reduction in all-cause mortality is because of a significant reduction in hemorrhagic stroke and intracranial bleeding that occurs when we are using the newer therapies, although there is a slightly increased risk of gastrointestinal bleeding.”

The lecture, titled ‘A New Era of Anticoagulation’, was accredited locally by the Qatar Council for Healthcare Practitioners-Accreditation Department (QCHP-AD) and internationally by the Accreditation Council for Continuing Medical Education (ACCME).