The introduction of new medications to the anticoagulation landscape has brought about changes in treatment patterns, which may result in confusion with regard to effective anticoagulation management among patients and practitioners without proper access to information. Now that the NOACs have been shown to be effective and safe for use in clinical trials, Phase IV research is needed to investigate the real-world impact of these new drugs. The availability of a large, variable-rich and non-interventional dataset such as GARFIELD-AF may be used to advance our understanding of how the various types of anticoagulation compare with one another in their uptake and in daily management by patients, and which are consequently most suitable for real-life scenarios.
The preliminary data, with a focus on the Netherlands in this manuscript, show remarkable changes over time, with substantial variation across countries. Within the Netherlands, a very gradual uptake of NOACs has been observed compared with many other countries, including its neighbour Belgium where only approximately 20 % of patients with AF are still on VKA therapy (data not shown). This rather striking contrast between the two countries may be explained by the presence of a network of anticoagulation clinics spanning the Netherlands; this situation is quite different in Belgium as well as many other countries around the globe.
Among the consecutive cohorts, it should be noted that a fairly fixed proportion of patients remain untreated; the proportion of patients on aspirin appears to diminish in time, which may in part be caused by a relatively larger proportion of patients who receive an NOAC. Due to the nature of this study we cannot, however, provide explanations as to the decision-making processes that underlie these apparent changes in prescriptions.
When compared with the pooled world data, it appears that many patients in the Netherlands are prescribed oral anticoagulants; usually they are prescribed VKA, in view of the data presented in this paper. Obviously, VKA therapy is challenging: it requires patient-specific titration and periodic readjustment of the prescribed dose throughout therapy to properly manage the patient’s prothrombin time, reflected by the INR. VKA therapy is reasonably effective and safe within an INR range of 2–3 (in the Netherlands, a slightly higher range of 2.5–3.5 was preferred until recently) , considering a time within therapeutic range (TTR) of >70 % as optimal. According to the Rosendaal linear interpolation technique, the average TTR (INR range 2.5–3.5) for long-term users in the Netherlands is 81 % . The fact that VKA management requires frequent hospital visits and blood sampling may also impact in different ways on the inclination or ability of patients to initiate or continue therapy . Finally, VKAs have a host of food-drug and drug-drug interactions , complicating their management still further. In light of these issues, NOAC therapy offers many practical advantages: NOACs are prescribed in fixed doses, do not require continuous monitoring and have fewer interactions with food and drugs. In spite of the potential advantages of NOACs there are still some hurdles, including the persistent risk of major bleeding complications while on oral anticoagulation . NOACs remain under particular scrutiny in this regard [16, 17], owing to the absence of effective antidotes to factor Xa and direct thrombin inhibitors until recently . However, this situation is changing; a dabigatran antidote, idarucizumab, was approved by the FDA at the end of last year and is currently registered in the Netherlands too .
Perhaps the biggest impediment to treatment efficacy is poor therapy compliance. Although non-compliance patterns are diverse (e. g. regular short gaps in medication-taking versus infrequent longer spells), the impact on treatment efficacy often amounts to the same negative result. This is particularly so for the NOACs, which have much shorter half-lives than VKAs . Research indicates that suboptimal dabigatran adherence is associated with increased risk for all-cause mortality and stroke . This underlines the pressing need to provide good information to patients, but also to organise integrated antithrombotic care for long-term users of anticoagulants. Integrated antithrombotic care has recently been recommended as standard care in the nationally endorsed National Standard of Integrated Antithrombotic Care 2.0 (LSKA 2.0) .
The GARFIELD-AF registry has spawned several research articles that attest to the usefulness of the dataset in informing better anticoagulation practices. An analysis of the characteristics of the first cohort (n = 10,614, spanning 19 countries, enrolment period December 2009 to October 2011) indicates that at the end of the VKA-only era, anticoagulant therapy was underused in patients at high risk of stroke and overused in those at low risk . Another, more recent analysis confirmed these findings and also showed that more women than men were at moderate-to-high risk of stroke . GARFIELD-AF is among the largest and longest-running of several recent large-scale observational registries charting anticoagulation use and outcomes in AF.
National initiatives, such as the PINNACLE (Practice INNovation And Clinical Excellence), ORBIT-AF (Outcomes Registry for Better Treatment of Atrial Fibrillation), the Paul Coverdell National Acute Stroke Registry, AFNET (the German Competence Network on Atrial Fibrillation) and regional initiatives, such as PREFER in AF (Prevention of thromboembolic events – European Registry in Atrial Fibrillation) supplement more broad-scoped registries with a localised focus, including RealiseAF (Real-life global survey evaluating patients with atrial fibrillation), RecordAF (REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation) and GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation).
Large registries such as those described above present a number of real benefits to the various groups in society involved in antithrombotic therapy of AF patients. Healthcare systems will be able to better analyse budgetary impacts in the continuously evolving anticoagulation landscape; clinicians are aided in customising therapy trajectories to best benefit their patients, based on the myriad factors that contribute to interindividual variability (e. g. non-compliance risk factors, comorbidity profiles, renal function); the data could also be used to promote patient understanding of the various competing treatment options and their associated risks and benefits. In the Netherlands, where such awareness is still not optimal, the impact of the GARFIELD-AF registry and others of its ilk could be beneficial.