Fanny Ofek1, Samuel Bar Chaim2, Nirit Kronenfeld3, Tomer Ziv-Baran4, Matitiahu Berkovitch5. 1. Pharmacy Department, Assaf Harofeh Medical Center, Zerifin, Israel. Electronic address: fanny.ofek@gmail.com. 2. Emergency Department, Assaf Harofeh Medical Center, Zerifin, Israel. 3. Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel. 4. Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zerifin, Israel.
Abstract
PURPOSE: Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. METHODS: The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions. FINDINGS: No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001). IMPLICATIONS: Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.
PURPOSE: Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. METHODS: The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions. FINDINGS: No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxabanpatients and 78.3% of apixabanpatients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001). IMPLICATIONS: Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.
Authors: Andrea Huppertz; Caspar Grond-Ginsbach; Chris Dumschat; Kathrin I Foerster; Jürgen Burhenne; Johanna Weiss; David Czock; Jan C Purrucker; Timolaos Rizos; Walter E Haefeli Journal: BMC Pharmacol Toxicol Date: 2019-08-29 Impact factor: 2.483
Authors: Alexander Kaserer; Andreas Schedler; Burkhardt Seifert; Donat R Spahn; Jan-Dirk Studt; Philipp Stein Journal: Perioper Med (Lond) Date: 2019-11-20