Elderly people are inherently sensitive to the pharmacological activity of rivaroxaban: implications for DOAC prescribin
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Elderly people are inherently sensitive to the pharmacological activity of rivaroxaban: implications for DOAC prescribing Emmanouela Kampouraki1 · Salah Abohelaika1 · Peter Avery2 · Tina Biss1 · Paul Murphy3 · Hilary Wynne4 · Farhad Kamali5 Accepted: 26 October 2020 © The Author(s) 2020
Abstract According to both trial and clinical data on direct oral anticoagulants (DOACs) elderly patients are at greatest risk of bleeding. It is unclear whether age intrinsically affects anticoagulation response. To investigate the age-related sensitivity to DOACs, we compared the pharmacological activity of the direct factor Xa inhibitor, rivaroxaban, between young and elderly subjects ex-vivo. 36 fit elderly and 30 fit young subjects [median (IQR) age: 83(75–87) vs 30(26–38) years] provided a blood sample. Clotting parameters were measured in the resultant plasma samples incubated with rivaroxaban (100–500 ng/ml). Parametric, non-parametric tests and regression lines adjusted for rivaroxaban concentration and baseline values were used to compare data. Rivaroxaban produced a greater prolongation of both Prothrombin Time (PT) and modified Prothrombin Time (mPT) (both p < 0.001) in the elderly compared to young subjects (with difference in mean PT increasing from 1.6 to 6.1s and for mPT from 23.5 to 71.1s at 100 ng/ml and 500 ng/ml plasma rivaroxaban concentration, respectively). Factor X and factor II activity was significantly lower in the elderly in the presence of rivaroxaban (p < 0.001 for both). Rivaroxaban prolonged time-based parameters and suppressed the amount of thrombin generation to a significantly greater extent in the elderly compared to young subjects [%change from baseline for Endogenous Thrombin Potential (ETP): − 35.0 ± 4.4 vs − 29.8 ± 7.4 nM*min; p = 0.002]. The use of validated DOAC assays will be of considerable benefit for monitoring elderly patients who, because of their increased sensitivity to rivaroxaban, may require lower doses of the drug for therapeutic anticoagulation. Keywords Aged · Anticoagulants · Blood coagulation tests · Rivaroxaban
Highlights • Elderly patients on DOACs are at highest risk of bleeding
complications.
* Farhad Kamali [email protected] 1
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
2
School of Mathematics, Statistics and Physics, Newcastle University, Newcastle upon Tyne, United Kingdom
3
Department of Hematology, Newcastle University, Newcastle upon Tyne, United Kingdom
4
Older People’s Medicine, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
5
Translational and Clinical Research Institute, Newcastle University, and Newcastle upon Tyne Hospitals, NHS Foundation Trust, NE1 7RU Newcastle upon Tyne, United Kingdom
• This study investigated whether age intrinsically affects
anticoagulation response to rivaroxaban.
• Elderly subjects are inherently more sensitive to rivar-
oxaban compared to young subjects.
• Due to age-related increase in sensitivity, elderly patients
may requir
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