ESC 2022: What Do the Latest Real-World Data Say About the Use of DOACs in Atrial Fibrillation?

A bridge between studies and routine practice

In clinical studies, we have a highly controlled environment, homogeneous study populations with good adherence to treatment, and patients with comorbidities are often excluded. In routine practice, on the other hand, we encounter a heterogeneous patient population, unselected by specific criteria, living in a less controlled environment, with varying numbers and types of comorbidities and unknown compliance. Analyses of real-world data thus represent a bridge between clinical studies and routine practice.

The main sources of these data are retrospectively analyzed databases and electronic health records, as well as retrospectively and prospectively analyzed registries and phase IV studies or post-marketing surveillance data. When evaluating real-world studies, key considerations include methodological criteria, the availability of dosage information, and data collection limitations. Such analyses provide insights into the safety profiles and efficacy of treatment strategies in clinical practice, where the patient population composition is not selectively influenced.

Real-world insights on DOACs

In a large real-world study conducted by the U.S. Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (FDA/CMS), it was found that the use of any direct oral anticoagulant was associated with lower risks of stroke compared to the vitamin K antagonist (VKA) warfarin [1]. Numerous retrospective analyses of real-world data further provide comparative safety and efficacy data among individual DOACs.

GARFIELD registry

The international prospective GARFIELD-AF registry includes 57,262 patients with newly diagnosed AF and at least one risk factor for stroke, treated at more than 1000 centers in 35 countries. Analysis of data from 2-year follow-up in this registry showed a significantly lower rate of major bleeding and all-cause mortality with DOACs compared to VKAs (non-hemorrhagic stroke/systemic embolism rates were similar between DOACs and VKAs), with dabigatran achieving the best results in these outcomes (0.7 major bleeding events per 100 patient-years with dabigatran vs. 1.0 with FXa inhibitors vs. 1.4 with VKAs; all-cause mortality was 3.3 vs. 3.7 vs. 4.8 events per 100 patient-years) [2].

Innovative GLORIA-AF registry

Professor Gregory Y. H. Lip from Liverpool University subsequently presented fresh data from the innovative GLORIA-AF registry [3, 4]. This is a prospective global study providing long-term comparative data on the use of oral anticoagulants in an unselected population and without patient selection based on existing conditions or other criteria. It includes about 56,000 patients from nearly 50 countries in Europe, Asia, North America, Latin America, and Africa. It has three main objectives: to characterize patients with newly diagnosed AF and risk of stroke, describe thromboembolic treatment patterns in preventing stroke in these patients, and gather data on the safety and efficacy of DOACs compared to VKAs in routine patient care.

From data of 21,300 patients at 935 sites in 38 countries collected over 3 years, the following key points can be summarized:

• The relative risk of major bleeding was reduced by 39% with dabigatran compared to VKAs, and the relative risk of all-cause mortality was reduced by 22%. The risks of stroke or myocardial infarction (MI) were similar [3].
• Patients taking dabigatran had a 41% lower relative risk of major bleeding compared to those taking rivaroxaban. No significant difference was found in the risks of stroke, MI, all-cause mortality, or composite endpoints between the two drugs [4].
• Dabigatran had similar clinical outcomes as apixaban [4].

Analyses from GLORIA-AF provide data confirming the safety and efficacy of direct anticoagulation in a broad spectrum of patients with AF and comorbidities.

Eva Srbová
Editorial team for ProLékaře.cz

Sources:
1. Graham D. J., Baro E., Zhang R. et al. Comparative stroke, bleeding, and mortality risks in older Medicare patients treated with oral anticoagulants for nonvalvular atrial fibrillation. Am J Med 2019; 132 (5): 596–604, e11, doi: 10.1016/j.amjmed.2018.12.023.
2. Camm A. J., Fox K. A. A., Virdone S. et al. Comparative effectiveness of oral anticoagulants in everyday practice. Heart 2021; 107 (12): 962–670, doi: 10.1136/heartjnl-2020-318420.
3. Huisman M. V., Teutsch C., Lu S. et al. Dabigatran versus vitamin K antagonists for atrial fibrillation in clinical practice: final outcomes from phase III of the GLORIA-AF registry. Clin Res Cardiol 2022; 111 (5): 548–559, doi: 10.1007/s00392-021-01957-1.
4. Lip G. Y. H., Kotalczyk A., Teutsch C. et al. Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry. Clin Res Cardiol 2022; 111 (5): 560–573, doi: 10.1007/s00392-022-01996-2.
5. Halperin J. Real-world evidence: a bridge between trials and clinical practice. Enhancing the evidence: latest real-world insights into NOACs for AF. ESC Congress, Barcelona, 2022 Aug 28.
6. Huisman M. What do real-world analyses tell us about NOACs? Enhancing the evidence: latest real-world insights into NOACs for AF. ESC Congress, Barcelona, 2022 Aug 28.
7. Lip G. Y. H. GLORIA-AF: New phase III data from this innovative registry program. Enhancing the evidence: latest real-world insights into NOACs for AF. ESC Congress, Barcelona, 2022 Aug 28.