Presentation Details
| Factor II and X (Fiix) Monitored Warfarin Is More Effective Than PT-INR Monitored Warfarin and Direct Oral Anticoagulants in Patients Anticoagulated Long-Term for Non-Valvular Atrial Fibrillation.The Greater Reykjavik Oral Anticoagulation (GROAC) Study. Arnar B.Ingason1, 2, Brynja R.Gudmundsdottir1, Ragnar Palsson1, 3, 4, Arnar S.Agustsson1, Edward Rumba1, Daniel A.Palsson1, Indridi Reynisson1, Sigrun H.Lund5, Johann P.Hreinsson6, Einar S.Bjornsson1, 5, Pall T.Onundarson1, 5. 1Landspitali National University Hospital, Reykjavik, Iceland.2University of Vermont, Burlington, VT, USA.3Massachusetts General Hospital, Boston, MA, USA.4Harvard University, Boston, MA, USA.5University of Iceland, Reykjavik, Iceland.6Sahlgrenska University, Gothenburg, Sweden |
Abstract
Background: The antithrombotic effect of warfarin depends on reducing factors (F) II and X but PT-INR is influenced not only by reductions in factors FII and FX but also in FVII. Due to short half-life, FVII drives short-term PT-INR variability and, therefore, confounds warfarin management. The FII and FX (Fiix) test is only affected by FII and FX and ignores FVII. Fiix-monitored warfarin (Fiix-warfarin) has been shown to reduce thromboembolism (TE) without increasing major bleeding (MB) compared to PT-INR monitored warfarin (PT-warfarin) in mixed patient populations. Aim: Comparison of effectiveness and safety of Fiix-warfarin, PT-warfarin, apixaban, rivaroxaban, and dabigatran in non-valvular atrial fibrillation (AF). Methods: Real-world TE and MB incidence was compared in all 6,417 AF patients residing in the Greater Reykjavik Area from 2014-2019 treated long-term (>6 months) with Fiix-warfarin (n=1,257), PT-warfarin (n=1,904), apixaban (n=1,171), rivaroxaban (n=1,536) or dabigatran (n=549). Patients were identified through a national outpatient prescription registry. All patients diagnosed with major events were referred to a single hospital system for diagnosis and treatment. Patient data and adverse events were extracted by searching the single electronic health record system used in the area as well as radiology and endoscopy records. Main outcomes were total TE, total TE or death from any cause, and MB by ISTH definition. Inverse probability weighting was used to yield balanced study groups. Outcomes were compared using Cox regression models, adjusting for baseline differences in patient groups. Results: The propensity score weighted total TE with Fiix-warfarin was 1.1% per patient year (ppy), lower than with PT-warfarin (1.9%, adjusted hazard ratio (AHR) 1.86 [95% confidence interval (CI) 1.19-2.91]), apixaban (1.9%, AHR 1.94 [1.13-3.32]), dabigatran (2.2%, AHR 2.19[1.18-4.06]) or rivaroxaban (1.6%, AHR 1.58 [0.96-2.61]), see figure (left panel). The composite outcome of any TE or death with Fiix-warfarin was 2.9% ppy, which was lower than with PT-warfarin (3.8%; AHR 1.31: 1.00-1.72), apixaban (4.4%; AHR 1.56:1.11-2.16), dabigatran (4.6%; AHR 1.57:1.07-2.30) or rivaroxaban (4.5%; AHR 1.54:1.13-2.08), see figure (right panel). Acute myocardial infarction (AMI) occurred at a 2.6-3.3 fold higher rate with PT-warfarin, apixaban, dabigatran and rivaroxaban than with Fiix-warfarin whereas stroke and systemic embolism occurred at similar rates. The MB incidence was 2.7% ppy with Fiix-warfarin and did not differ significantly between the different OACs (PT-warfarin 2.5%; AHR 0.89 [0.65-1.22], apixaban 2.4%; AHR 0.86 [0.57-1.30], Dabigatran 2.2%; AHR 0.77 [0.48-1.23] and rivaroxaban 3.0%; AHR 1.07 [0.76-1.50]). The total intracranial hemorrhage rate was similar with the different OACs: 0.6% ppy with Fiix-warfarin vs PT-warfarin 0.5%; AHR 0.70 [0.35-1.37], apixaban 0.3%; AHR 0.53 [0.18-1.55], Dabigatran 0.6%; AHR 0.82 [0.22-2.06] and rivaroxaban 0.4%; AHR 0.59 [0.24-1.48]. Hemorrhagic stroke occurred in 0.1-0.2% ppy except with dabigatran (0.5%, NS). Conclusions: In all-inclusive real-world practice, anticoagulation with Fiix-monitored warfarin was associated with lower incidence of total TE and composite total TE or death but not increased MB compared to patients on traditional PT-INR monitored warfarin, apixaban, dabigatran or rivaroxaban. Fiix-monitoring might replace the old PT-INR for the purpose of warfarin monitoring and become a new reference in oral anticoagulation studies.
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