Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study

Objective: This study aimed to evaluate the safety of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) during daily clinical practice.
Methods: This was a prospective study conducted between January 01, 2016, and April 01, 2017, in patients aged ≥18 years with a diagnosis of NVAF. We performed the study in 9 clinical centers from different regions of Turkey, and the mean follow-up period was 12+2 months. We investigated major and minor bleeding events of DOAC.
Results: A total of 1807 patients with NVAF were enrolled. The mean age of the patients was 73.6±10.2 years, CHA2DS2-VASc score was 3.6±1.4, and HAS-BLED score was 2±1.2. The most frequently prescribed DOAC was dabigatran 110 mg bid in 409 (22.6%) patients. The patients on apixaban 2.5 mg bid were older (p<0.001). Patients on rivaroxaban 15 mg od also had a higher prevalence of chronic renal failure, 46 (16.7%) patients. A total of 205 (11.4%) bleeding events were observed; among these, 34 (1.9%) patients had major bleeding and 171 (9.4%) patients had minor bleeding. The major and minor bleeding events were 2/273 (0.7%) and 30/273 (10.9%) in patients receiving dabigatran 150 mg bid, 13/409 (3%) and 44/409 (10.7%) in patients receiving dabigatran 110 mg bid, 4/385 (1%) and 42/385 (10.9%) in patients receiving rivaroxaban 20 mg od, 8/276 (2.9%) and 27/276 (9.7%) in patients receiving rivaroxaban 15 mg od, 3/308 (0.9%) and 14/308 (4.5%) in patients receiving apixaban 5 mg bid, 4/156 (2.5%) and 14/156 (9%) in patients receiving apixaban 2.5 mg bid, respectively. The total bleeding events were 17 (5.6%) in patients receiving apixaban 5 mg, less than those receiving other DOACs. On multivariate analyses, rivaroxaban 20 mg od (p=0.002), ATRIA and HAS-BLED scores, and peripheral artery disease were independent indicators of bleeding. The most frequent location of major bleeding was the gastrointestinal system (GIS) [17 (0.9%) patients], and the most frequent location of minor bleeding was the gingiva [45 (2.5%) patients].
Conclusion: This study showed that similar results as the previous real-life study; however, we had some different results, such as the GIS tract bleeding was more frequent in patients receiving dabigatran 110 mg bid. The major and intracranial bleeding events were similar for different DOACs; and among DOACs, only rivaroxaban 20 mg od was associated with a high risk of bleeding.

DOAKlarda bir yıllık gerçek yaşam, major ve minör kanama verileri: (NOAC-TURK study).

Öz.
Amaç: Nonvalvüler atrial fibrilasyon (NVAF) hastalarında direkt oral antikoagülanların güvenilirliğinin değerlendirilmesi.
Metod: Ocak 2016 ve Nissan 2017 tarihleri arasında yapılan prospektif çalışmada,18 yaşından büyük, direkt oral antikoagulan tedavi altındaki NVAF tanılı hastalar incelendi.Türkiyenin farklı bölgerlerinde yapılan çalışmada ortalama takip süresi 12±2 aydı.Mayor ve minor kanama olayları araştırıldı.
Bulgular: Toplamda 1807 katılımcı kaydedildi. Ortalama yaş (age=73.6 ± 10.2, 39% male, mean CHA2DS2-VASc score =3.6 ± 1.4, HAS-BLED score=2 ± 1.2).En sık reçete edilen DOAK dabigatran 110 mg bid idi 409 (22.6%).Apiksaban 2.5 mg bid alan hastalar en yaşlı gruptu(p<0.001). Rivaroksaban 15 mg alan hastalarda, kronik böbrek yetersizliği oranı daha fazla idi 46(16.7%)). Toplam 205(11.4%) hastada kanama olayı gözlendi. Bunların arasından 34 tanesi (1.9%) major, 171 tanesi (9.4%) minör kanama idi. Sırası ile dabigatran 150 mg alan grupta kanama olayı 2/273(0.7%) major, 30/273(10.9%) minör, dabigatran 110 mg’da major 13/409(3%) ve minör 44/409(10.7%). Rivaroksaban 20 mg’da 42/385(10,9%) ve 4/385(1%), rivaroksaban 15 mg’da 8/276(2.9%) ve 27/276 (9.7%). Apiksaban 5 mg’da 3/308(0.9%) ve 14/308(4.5%), apiksaban 2.5 mg’da 4/156(2.5%) ve 14/156(9%). Apiksaban 5mg ile olan toplam kanama 17(5.6%) diğer DOAK’lardan daha azdı. Ancak bu ilişki çok değişkenli analizde gösterilemedi. Dabigatran 110 mg da toplam kanama ve gastrointestinal sistem (GIS) kanama oranı daha yüksekti. Çok değişkenli analizde,rivaroksaban 20 mg kanama riski için bağımsız bir göstergeydi (HR=1.760, (CI=1.228 - 2.524) P=0.002). ATRIA ve HAS-BLED skorları ile periferik arter hastalığı kanama riski için diğer bağımsız göstergelerdi. Çalışmamızda en sık major kanama odağı GIS 17 (0.9 %) iken, gingiva (45 (2.5%) ise en sık minör kanama odağı idi.
Sonuç: Bu çalışma, gerçek yaşam çalışmalarına benzer sonuçlar göstermekteydi. Rivaroksaban 20 mg, kanama için bağımsız bir risk faktörüydü.