Patients With Atrial Fibrillation at Risk of Stroke.
GARFIELD (Global Anticoagulant Registry in the FIELD).
Lord Ajay Kakkar,
en representación del Comité Directivo y de Publicaciones del Registro GARFIELD/On behalf of the Global GARFIELD Steering Committee & Publication Committee.
Global GARFIELD Steering Committee/Publication Committee.
Jean-Pierre Bassand (France), David Fitzmaurice (Birmingham, UK);
Samuel Goldhaber (Boston, MA. USA), Shinya Goto (Kanagawa, Japan),
Sylvia Haas (Munich, Germany), Werner Hacke (Berlin, Germany),
Lord Ajay Kakkar (London, UK), Gregory Lip (Birmingham, UK)
Lorenzo Mantovani (Naples, Italy), Alexander G G Turpie (Hamilton, ON, Canada), Freek Verheugt (Amsterdam, The Netherlands).
Trombosis Research Institute.
Emmanuel Kaye Building, Manresa Road
SW3 6LR – Tel: +44(0)20 7351 8300
Fax: +44(0)20 7351 8324
Chelsea, London. United Kingdom.
Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia, affecting 1–2% of the population, and its prevalence is anticipated to increase [1,2]. Patients with AF are more likely to have a severe stroke, and if they do, are twice as likely to die within 1 year  as those without the arrhythmia [4,5]. Hospitalizations are frequent, quality of life and exercise capacity are reduced , and ventricular function is impaired . Yet current AF management is often inadequate, with wide variations reported in physician adherence to evidence-based recommendations, leaving vulnerable patients at risk of a fatal or disabling event [5,8-11].
Clinical trials have demonstrated the effectiveness of oral anticoagulants in the prevention of stroke and systemic embolism in patients with non-valvular AF , the most widely used being the vitamin K antagonists (VKAs) and aspirin. The VKAs have a narrow therapeutic window, leaving patients at risk of an AF-related stroke or bleed if the target international normalized ratio (INR) is not maintained; they have a high degree of inter- and intra-patient variability; require routine laboratory monitoring; interact with a large number of foods and drugs; and have a slow onset and offset of action, particularly in the elderly. The resultant reluctance among clinicians to give oral anticoagulant therapy to patients for whom it is appropriate – because of contraindications, fear of bleeding, or inability to comply with monitoring or dosing – represents a lost opportunity to prevent stroke.
As a consequence of these limitations, considerable research efforts have been directed toward new oral anticoagulants that do not have the disadvantages associated with the VKAs. These agents fall broadly into two classes: the oral direct thrombin inhibitors (e.g., dabigatran etexilate  and AZD0837) and the oral factor Xa inhibitors (e.g. rivaroxaban, apixaban , edoxaban, betrixaban, and YM150). Promising results have been reported recently from the Randomized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate (RE-LY) study , and the double-blind phase 3 Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial . These novel agents provide alternatives to warfarin, changing the paradigm of care for non-valvular AF.
In clinical trials of novel anticoagulants versus warfarin for stroke prevention in non-valvular AF, regulatory authorities mandate very tight control of anticoagulant therapy. This strategy results in lower rates of therapeutic failure than usually seen in real-life clinical practice. Thus accurate assessment of the value of novel antithrombotic drugs is more difficult. There is, therefore, a need for an international observational registry of patients treated in everyday clinical practice to test the external validity of the trial data and provide complementary information to that derived from the trials.
The Global Anticoagulant Registry in the FIELD (GARFIELD) Registry is an observational, multicentre, international prospective study designed to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF and at least one additional risk factor for stroke . The aim is to enroll 55000 patients at more than 1000 centers in 50 countries over 4 years in five independent, sequential, prospective cohorts, each comprising approximately 10000 adult patients (age ≥18 years) diagnosed with non-valvular AF according to standard local procedures within the past 6 weeks and ≥1 additional, investigator-defined risk factor for stroke. The registry will include ‘incident’ patients who are started on oral anticoagulants or other pharmacological therapy for the prevention of thromboembolic stroke, as well as patients receiving no such therapies. The objectives of the registry are to describe ‘real-life’ treatment patterns; to assess rates of stroke and systemic embolism; and to assess the outcomes of these patients with specific reference to the incidence of bleeding complications, therapy persistence (including discontinuation, interruption, and changes of therapy regimen), and fluctuations over time in the INR for patients on VKAs. The registry is limited to patients with newly diagnosed AF, in order to provide a complete overview of the management of such patients through the course of their disease.
Investigator sites will be representative of the distribution of care settings and geography in each participating country. A sufficient number of sites, both globally and on a national level, will be identified from hospital, community, and anticoagulation clinic settings to ensure proportional representation of AF treating care settings in all countries. Sites will be contacted randomly within the identified care settings and selected following a qualification call. Patients will be identified from multiple sources including office-based specialists, hospital departments (neurology, cardiology, geriatrics, internal medicine, and emergency departments), anticoagulant clinics, stroke units, and general or family practice settings. The identifying clinician will register the patients using an electronic case report form. Physicians involved in the initial diagnosis of AF may transfer or refer the patients to other physicians, who will treat and follow up the patients for the registry. Thereafter, data on outcomes relevant to the registry will be collected from five clinical sources associated with the patient: the hospital, emergency department, anticoagulation clinic, stroke unit, and office-based settings such as general or family practitioners, cardiologists and internists, through review of patient notes and clinical records.
At baseline, available data will be collected on the following: patient demographics, medical history, nature of AF (paroxysmal versus persistent versus permanent), date and method of diagnosis, symptoms, and treatment decisions. The application of a patient satisfaction scale (for those on antithrombotic therapy) is planned for later cohorts. The following additional information will be collected in a validation cohort from 6 months up to 2 years prior to the screening visit: past treatments; changes in treatments; past INR values, dates of monitoring, and past events.
Follow-up in terms of data collection will take place at 4, 8, 12, 16, 20, and 24 months and will be obtained from the enrolling sites; patients will not be required to attend 4-monthly clinic visits. The aim will be to capture all planned and unplanned visits, interruptions to treatment, and clinical events, and outcomes will include clinical events, therapy persistence, and healthcare utilization.
No feedback or comparative data will be provided to participating sites in order to minimize any impact on normal practise. However, involvement in a study, albeit one that does not alter practice patterns, may ultimately improve practice at participating sites. A validation cohort of 4970 patients has been enrolled into the first cohort, to describe the nature and characteristics of care for patients at participating sites prior to registry initiation and to confirm either no or any change in baseline care as a result of each site’s participation in the registry. Comparison of the retrospective cohort with the first prospective cohort will serve to evaluate how far the initiation of the GARFIELD registry influenced AF management patterns on a site level.
In summary, the GARFIELD registry will provide unique and valuable insights into real-life patient risk profiles, treatment-initiation strategies, and the long-term clinical management and related outcomes of AF patients throughout the world. The inclusion of consecutive, treatment-naive patients with newly diagnosed non-valvular AF, irrespective of age and comorbidities or whether they receive anticoagulant therapy, will provide a representative perspective of AF management in unselected patient populations and across the spectrum of national healthcare systems. By capturing real-life risk stratification, management, and outcomes in AF patients, the registry will also allow evaluation of the application and effectiveness of currently available treatment guidelines and risk scores for stroke and bleeding . The registry may highlight deficiencies in available treatment options for specific patient populations; it will describe how therapeutic strategies, patient care, and outcomes evolve over time, as well as in the light of new treatment options that become available during the course of the registry. Finally, the GARFIELD database will offer unique global and national perspectives into the profiles of patients with AF including modifiable and other pathophysiological risk factors, related management strategies, and the clinical and economic effectiveness of therapeutic options in everyday clinical practice.
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Publication: May 2012