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Is the ideal anticoagulant a myth?

The ideal anticoagulant does not exist. In all likelihood it will never exist. In 2011, Favaloro and Lippi described the important characteristics of the ideal anticoagulant [1]. Among the list of traits were high efficacy with a wide therapeutic and safe window, oral administration with a rapid onset of action, a predictable anticoagulant effect and, importantly, does not need to be monitored. In this article, I will explore theoretically why chronically administered oral anticoagulants cannot fulfil the wish list criteria proposed by Favaloro and Lippi. I will also highlight the need for appropriate consideration of dose individualization and monitoring in order to optimize patient care. In 1999, Holford described the importance of identifying a target plasma concentration that can be used to guide drug therapy [2]. This concept can also be generalized to a target based on any biomarker related to drug response (e.g., clotting time). Importantly, when defining a target response, the probability that any given dosing regimen will be successful in achieving this target must be considered. This probability is related to the variability in the relationship between the concentration (or effect) of the drug and the chosen dosing regimen. This variability was attributed to ‘population-parameter variability’ and consisted of between-subject variability and within-subject variability. Like Favaloro and Lippi, Holford indicates that if the variability in response to a drug is less than a predefined safe level of variability, then the drug can be safely dosed without need for careful scrutiny of an individual’s biomarker response. If, however, the variability in response exceeds a safe level, then the dosing regimen would need to be individualized.