LETTER TO THE EDITOR Dabigatran levels in omeprazole versus pantoprazole-treated patients with atrial fibrillation: is there a difference? Tomáš Bolek 1 & Matej Samoš 1 & Ingrid Škorňová 2 & Martin Schnierer 3 & Peter Lipták 3 & Peter Bánovčin 3 & Lukáš Urban 1 & Ján Staško 2 & Peter Kubisz 2 & Peter Galajda 1 & Marián Mokán 1 Received: 3 January 2019 /Accepted: 5 February 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 To the Editor: Proton pump inhibition (PPI) administrated with dabigatran etexilate reduces the risk of gastrointestinal (GI) bleeding on long-term dabigatran therapy [1]. However, we have previously demonstrated [2] that PPI (with omeprazole or pantoprazole) significantly reduces the trough and peak on- treatment levels in dabigatran-treated patients with atrial fibril- lation (AF). Similar observation of significantly lower dabigatran levels in PPI-treated patients was subsequently published in Japanese patients with AF [3]. Now, it is not entirely clear whether this is a Bclass effect^ or a Bdrug effect.^ In fact, there are differences in PPI pharmacokinetics, such as differences in bioavailability, elimination half-life, and metab- olism, which may translate into differences in interaction [4]. Therefore, we decided to compare the effect of omeprazole PPI versus pantoprazole PPI on dabigatran etexilate trough and peak levels in patients with AF. We performed a pilot, prospective, observational study in patients with AF on long-term dabigatran etexilate therapy (DT). Thirty-four consecutive presentations of patients (19 men, 15 women, mean age 76 years, ranging from 63 to 89) with AF on DT were enrolled to this study. The exclusion criteria were the same as in our previous PPI/dabigatran inter- action study [2]. The average length of taking dabigatran be- fore the assessment of dabigatran levels was 100.2 days. PPI with omeprazole dosed 20 mg twice daily was administrated in 12 patients, PPI with pantoprazole dosed 40 mg once daily was administrated in 12 patients, and in 10 patients, no PPI was administrated. To maintain the conditions of real-life clin- ical practice, the decision on PPI strategy was left to the at- tending physician (and was based on the individual estimation of gastrointestinal bleeding risk on long-term anticoagulation). Blood samples were taken 12 h after a pre- vious drug dose administration (at 7:00 AM, trough sample) and 2 h after the next drug dose administration (at 9:00 AM, peak sample); patients were tested on the fifth day of their in- hospital stay, and were fasting before the blood sampling. Dabigatran levels were measured with the Hemoclot Thrombin Inhibitor Assay (Hyphen BioMed, Neuville sur- Oise, France) [5]. This research was performed according to ethical standards and was approved by the local ethical com- mittee. All patients agreed with study participation and signed a written informed consent form before blood sampling. STATISTICA v 5.0 (StatSoft, Tula, OK) was used for the analysis of all data. Data were in the first step tested for nor- mality with the Shapiro–Wilk test. Group effects were tested with t test in the case of normally distributed data or with the Mann–Whitney U test when data distribution was asymmet- rical. The significance of p ≤ 0.05 was considered as a criteri- on for comparison between data sets with equal and unequal variances. First, there were no significant differences in basic de- mographic data, concomitant medication, and duration of DT (Supplementary material 1) between omeprazole- treated patients, pantoprazole-treated patients, and patients without PPI. Second, comparing omeprazole-treated pa- tients with patients without PPI (Table 1), there were signif- icant differences in dabigatran trough (62.4 ± 51.1 ng/mL Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-019-02647-8) contains supplementary material, which is available to authorized users. * Matej Samoš matej.samos@gmail.com 1 Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59 Martin, Slovak Republic 2 National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic 3 Department of Gastroenterology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic European Journal of Clinical Pharmacology https://doi.org/10.1007/s00228-019-02647-8