In the introductory sentence, the authors of the very interesting article (1) point out that patients with nonvalvular atrial fibrillation or venous thromboembolism require vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) in “therapeutic doses”.
The differentiation of the VKA group based on international normalized ratio (INR) values in the prospective study, however, revealed that 33% of the patients are below the therapeutic INR range of 2–3, and 38.1% of the patients are above INR 3 (the INR upper limit after mechanical valve replacement would be 3.5).
With measured INR values down to 1.65, it is worth discussing whether these underdosed patients even fit into a study on the desired therapeutic anticoagulation. Can a patient with an INR of 1.65 be considered as having effective anticoagulation? Studies on the effect of a low-level oral anticoagulation (INR value ≤ 1.5) have expressly not recommended this dose level.
On the other hand, patients with an INR value >3 could already be at an increased risk of bleeding and mortality due to this overdose alone. There are different statements in the literature on the risk of bleeding in higher VKA dose ranges. Some authors refer to an increase in the risk of intracranial bleeding with an INR value > 3.0 (and especially > 3.5) (2, 3). In contrast, however, there are also statements in the literature that the risk of bleeding only increases rapidly with an INR value of 5 (4).
Therefore, it is worth discussing whether patients who were not “therapeutically dosed” with VKA should be compared to those who received DOAC in the correct dose, and whether this should be included in the comparative assessment of mortality rates.
Wouldn’t it be better to compare only the VKA patients in the recommended therapeutic INR range (of 2.0 to 3.0 or 3.5) with the DOAC patients who received the correct dose?
Dr. med. Gerrit Müntefering
Moers, Germany, firstname.lastname@example.org
Conflict of interest statement
The author declares that no conflict of interest exists.
|1.||Lindhoff-Last E, Herrmann E, Lindau S, et al.: Severe hemorrhage associated with oral anticoagulants—a prospective observational study of the clinical course during treatment with vitamin K antagonists or direct oral anticoagulants. Dtsch Arztebl Int 2020; 117: 312–9 VOLLTEXT|
|2.||Oden A, Fahlen M, Hart RG: Optimal INR for preventing of stroke and death inartrial fibrillation: a critical appraisal: Thromb Res 2006; 117: 493–9 CrossRef MEDLINE|
|3.||Camm AJ, Kirchhof P, Lip GY, et al.: Guidelines for the management of atrial fibrillation: the Task Force for the management of Atrial fibrillation of the European Society of Cardiology (ESC). Europace 2010; 12: 1360–420 CrossRef MEDLINE|
|4.||Niederer A, Wuillemin WA, Moerlosse PD: Orale Antikoagulation: Praktisches Vorgehen. Schweiz Med Forum 2001; 17: 425–30 CrossRef MEDLINE|