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Safety of once- or twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation: A NOAC-TR study

Sadık Volkan Emren, Mehdi Zoghi, Rida Berilgen, İbrahim Halil Özdemir, Oğuzhan Çelik, Nurullah Çetin, Asım Enhoş, Cemal Köseoğlu, Abdurrahman Akyüz, Volkan Doğan, Fatih Levent, Yüksel Dereli, Tolga Doğan, Özcan Başaran, Ilgın Karaca, Özkan Karaca, Yılmaz Ömür Otlu, Çağlar Özmen, Selvi Coşar, Mutlu Sümerkan, Erdal Gürsul, Sinan İnci, Ersel Onrat, Oktay Ergene


Once-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may increase patient adherence to treatment but may also be associated with a higher risk of bleeding. In this study, we investigated the adherence to once- or twice-daily dosing of NOACs and the risk of bleeding in nonvalvular atrial fibrillation (NVAF) patients. This multicenter cross-sectional study, conducted between 1 September 2015 and 28 February 2016, included 2214 patients receiving NOACs for at least 3 months, due to NVAF. Patients receiving once-daily or twice-daily NOAC doses were 1:1 propensity score matched for baseline demographic characteristics and the presence of other diseases. The medication adherence was assessed by the 8-item Morisky Medication Adherence Scale. Risk factors were investigated in relation to minor and major bleeding. The mean age of patients was 71 ± 10 years, and 53% of the patients were women. The medication adherence was lower in patients receiving twice-daily NOAC doses compared to once-daily-dose group (47% versus 53%, p = 0.001), and there was no difference between the groups in terms of minor (15% versus 16%, p = 0.292) and major bleeding (3% versus 3%, p = 0.796). Independent risk factors for bleeding were non-adherence to medication (OR: 1.62, 95% CI: 1.23–2.14, p = 0.001), presence of 3 or more other diseases (OR: 10.3, 95% CI: 5.3–20.3, p < 0.001), and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol) score (OR: 4.84, 95% CI: 4.04–5.8, p < 0.001). In summary, the once-daily dose of NOACs was associated with increased patient adherence to medication, while it was not associated with bleeding complications.


Daily dosing; bleeding; medication adherence; non-vitamin K antagonist oral anticoagulants; self-report; NOACs; nonvalvular atrial fibrillation; NVAF

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