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Patient management


Patient management and monitoring


The management of patients treated with NOACs has become easier than with VKAs; however, some basic principles still need to be followed


Sylvia Haas MD PhD Formerly Technical University of Munich, Germany


Although effective, there are several drawbacks to the use of VKAs. They have a narrow therapeutic window, resulting from genetic, environmental and dietary factors that affect the pharmacokinetic and pharmacodynamic profile.1


Regular coagulation monitoring


is, therefore, necessary to maintain the correct dose of VKA in each individual patient and an International normalised ratio (INR) range of 2.0–3.0 has been defined as the optimal therapeutic window for safety and efficacy for the vast majority of patients. VKAs also have a slow on- and offset of action, taking up to several days to reach the full antithrombotic effect and to restore normal coagulation after stopping therapy. Importantly, because VKAs are metabolised by cytochrome P450 (CYP) enzymes in the liver, they have significant interactions with other drugs, both prescription and over-the-counter.1 The development of non-vitamin K oral anticoagulants (NOACs) has overcome many limitations of VKAs (Table 1).


Key questions 24


Four NOACs have become available for different indications. The main indications include long-term anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation and treatment and secondary prevention of venous thromboembolism. There are five important questions about patient management and monitoring, and these are addressed in this article.


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Table 1: Characteristics differentiating NOACs from VKAs NOAC


characteristics


Fast onset and offset of action


Predictable mode of action


Fixed dose


No routine laboratory monitoring required


Wide


therapeutic window


Low risk of food and drug interactions


What does this mean in clinical practice?


No need for bridging with heparins in case of interventions


Safe and effective regulation of coagulation from the first dose and throughout therapy


No need for regular dose adjustment for the majority of patients


Saves healthcare costs through fewer hospital/physician visits and provides more convenience


Broad safety margin at a wide range of effective doses


Ease of use regardless of concomitant


medications and diet


Why is basic knowledge of the pharmacology of NOACs important? Health care professionals need to be familiar with some pharmacological characteristics of NOACs, which will help with the management of these compounds in clinical practice. In contrast to VKAs, their target in the coagulation cascade is limited to a single clotting factor: Factor Xa for apixaban, edoxaban and rivaroxaban; and Factor IIa (thrombin) for dabigatran. All NOACs are part of the class of direct oral anticoagulants, that is, their mode of action is provided by direct inhibition at the proteolytic active site of the target enzymes without cofactors, such as antithrombin as required for the mode of action of


heparins, or interference with the production of clotting factors, as for VKAs. Their half-lives and time to reach maximum activities after intake are comparable to subcutaneous injections of low molecular weight heparins (LMWHs), which is important to know in cases of switching to and from these parenteral anticoagulants owing to malabsorption of oral drugs or other clinical reasons. Based on the publications of Heidbuchel et al,2–4


key pharmacological characteristics of NOACs are summarised in Table 2.


How can patients be converted or switched from one anticoagulant to another?


The most important clinical scenarios are to switch a patient from a NOAC to a parenteral anticoagulant and vice versa or to convert a patient from VKA to NOAC and vice versa.


Switching from a NOAC to a parenteral anticoagulant and vice versa


If a patient taking a NOAC needs to be switched to a parenteral anticoagulant, for example, to subcutaneous administration of LMWH, LMWH can be initiated when the next dose of NOAC was due. This recommendation is based on the similar on- and offset of action of LMWHs and NOACs. The time to peak activity and the half-lives of NOACs are shown in Table 2 and the pharmacokinetic profile of LMWHs is comparable. The procedure of switching is represented graphically in Figure 1. Vice versa, the NOAC can be initiated when the next dose of LMWH would have been foreseen.5


some


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