GARFIELD-AF – Initiation of Antiplatelet Therapy Plus Oral Anticoagulation for Newly-diagnosed Atrial Fibrillation is Associated with Worse Outcomes than Anticoagulation Alone

– Insight into the results of the GARFIELD-AF registry, presented at the European Society of Cardiology Congress, Munich, Germany, 25–29 August 2018

Evidence suggests that in patients with atrial fibrillation (AF) and myocardial infarction (MI), or in those undergoing percutaneous coronary intervention, the use of antiplatelet (AP) therapy with anticoagulation is beneficial.¹ In these patients, the combination of an oral anticoagulant (OAC) with AP offers reduced bleeding risk and similar efficacy compared to the use of vitamin K antagonists in combination with AP.²

However, recent observations suggest that many patients with AF who are receiving AP therapy do not have a clinical indication that supports AP treatment in their management strategy.³

This study, using the Global anticoagulant registry in the field-atrial fibrillation (GARFIELD-AF) registry – the largest prospective global registry of over 55,000 patients with AF, recruited from 2010 to 2016 – sought to assess the merits of AP initiation in patients with newly diagnosed AF. It should be noted that this approach is not advocated by current guidelines;¹ this assessment was conducted in response to the observation in the GARFIELD-AF registry that a significant number of patients were prescribed AP treatment at the same time as initiating OAC therapy, following diagnosis of AF.

This analysis examined 25,815 patients with newly diagnosed AF and at least one risk factor for stroke, of whom 3,133 patients were initiated on AP and AOC therapy at entry into the study (22,682 initiated on OAC alone) across 1,317 sites in 35 countries. Patients who were receiving AP therapy for an indication other than stroke prevention were excluded.

Given that the GARFIELD-AF registry is an observational study, there were differences in the baseline characteristics of the two treatment arms. Patients initiated on AP plus OAC had higher incidences of heart failure, coronary artery disease, acute coronary syndrome (ACS), and more frequently a history of stroke, hypertension and hypercholesterolemia than patients entering the study on OAC alone. As expected, when unadjusted for baseline differences, there were more events per 100 patient years in the AP plus OAC group for all-cause mortality, stroke, bleeding and MI/ACS than in the OAC-alone group. After multivariate adjustment for baseline factors, the risk was markedly higher with AP plus OAC than with OAC alone for: all-cause mortality (hazard ratio [HR] 1.31; 95% confidence interval [CI] 1.05, 1.62), stroke (HR 1.60; 95% CI 1.08, 2.35), bleeding (HR 1.45; 95% CI 0.94, 2.23) and MI/ACS (HR 1.15; 95% CI 0.68, 1.94).

Interestingly, over half (56%) of the patients initiated on AP plus OAC did not have a diagnosis of coronary artery disease or peripheral artery disease. In these patients, compared with OAC alone, AP plus OAC therapy was independently associated with increased risk of all-cause mortality (HR 1.37; 95% CI 1.02, 1.85), stroke (HR 1.65; 95% CI 1.02, 2.65) and major bleeding (HR 1.54; 95% CI 0.91, 2.60).

The poor prognosis of patients initiated on AP plus OAC compared with those treated with OAC alone was not surprising, considering the baseline disease characteristics. However, the observation of poorer outcomes in patients given the combination following AF diagnosis but without indications supporting the use of AP therapy highlights an important practical consideration. Physicians need to fully consider if the immediate initiation of AP therapy in addition to OAC is appropriate in newly-diagnosed patients with AF – a perception among some physicians that ‘more is better’ – or whether OAC treatment alone is more appropriate in the absence of underlying vascular disease diagnosis.

References

1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962.
2. Sindet-Pedersen C, Lamberts M, Staerk L, et al. Combining oral anticoagulants with platelet inhibitors in patients with atrial fibrillation and coronary disease. J Am Coll Cardiol. 2018;72:1790–800.
3. Verheugt FWA, Gao H, Al Mahmeed W, et al. Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry. Eur Heart J. 2018;39:464–73.