The value and limitations of new oral anticoagulant plasma level assessments

Abstract

The class of new oral anticoagulants (NOACs) has been developed to provide reliable oral anticoagulation without the need for therapeutic drug monitoring. Based on phase I and II trials and pharmacokinetic and pharmacodynamic modeling, fixed drug doses have been selected for large phase III clinical trials for each currently available NOAC. In these trials, the use of the fixed dose without plasma level assessments was shown to be at least as effective and at least as safe as vitamin K antagonists with continuous therapeutic drug monitoring. Real world evidence reaffirms that the use of a fixed NOAC dose without plasma level assessment is safe and effective in a large variety of patients. Nevertheless, measurement of NOAC plasma levels can add information that may be useful in some clinical scenarios. This review discusses the possible use cases, the limitations, and the practical implementation of measuring NOAC plasma concentrations.

Efficacy and Safety of Non–Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation

“…9 The expected "normal" range of drug levels for each NOAC, derived primarily from descriptive post hoc reports of trial substudies, varies by dose and indication. Furthermore, data supporting the applicability of NOAC levels to guide dosing are lacking, 30 with society guidelines noting that evidence-based recommendations cannot be given about dose reduction or escalation in response NOAC level measurements. Thus, our results offer clinicians a more comprehensive overview of the clinical efficacy and safety of NOACs in these patient populations to guide decision-making.…”

Pharmacokinetic drug–drug interactions with direct anticoagulants in the management of cancer‐associated thrombosis

“…Moreover, a partial disconnect between exposure and outcome has been observed, explained largely by patient characteristics, which influence outcome as well. [15][16][17][18] Characteristics of relevant DOACs and LMWHs are summarized in Table 1.…”

“…Importantly, there is no evidence at this time that adjusting the DOAC dose in response to measured levels will actually lead to better clinical outcomes. 16,17 Others have promoted adjusting the dose based on measurements and/or expected drug interactions. 43 In general, we advise caution and do not promote this practice systematically.…”

“…For all DOACs, a broad range of on‐therapy plasma values has been observed in the landmark trials, albeit based on limited sampling and without measurements at the time of a clinical outcome. Moreover, a partial disconnect between exposure and outcome has been observed, explained largely by patient characteristics, which influence outcome as well 15–18 . Characteristics of relevant DOACs and LMWHs are summarized in Table 1.…”

“…(4) Plasma assessment can be performed to exclude DOAC overexposure or underexposure when combined with a strong inhibitor or inducer respectively. Importantly, there is no evidence at this time that adjusting the DOAC dose in response to measured levels will actually lead to better clinical outcomes 16,17 . Others have promoted adjusting the dose based on measurements and/or expected drug interactions 43 .…”