Oral anticoagulants and antiplatelets linked to poor outcome in atrial fibrillation

Combined oral anticoagulant and antiplatelet therapy has been linked to a worse prognosis than anticoagulation alone for newly-diagnosed atrial fibrillation patients without a clear indication for antiplatelets, according to new research.

The results from the GARFIELD-AF registry, presented recently at European Society of Cardiology (ESC) Congress, challenged the use of combined oral anticoagulant and antiplatelet therapy in patients with atrial fibrillation, especially those without an indication for antiplatelet therapy, said Professor Keith Fox, principal investigator, University of Edinburgh.

Nearly all patients diagnosed with atrial fibrillation should be started on oral anticoagulation to prevent stroke, according to 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with European Association for Cardio-Thoracic Surgery (EACTS). The addition of platelets was said to increase the risk of bleeding was not recommended unless required to prevent coronary or peripheral artery thrombosis. For example: in patients who have received a stent, had a myocardial infarction, or have peripheral artery disease.

Antithrombotic drugs

Anticoagulants and antiplatelets are both antithrombotic drugs, meaning they prevent the formation of blood clots. Anticoagulants do this by stopping the circulation of proteins needed for clotting, while antiplatelets stop platelets sticking together.

The researchers analysed the GARFIELD-AF registry3 to investigate whether adding an antiplatelet to oral anticoagulation therapy in those without a clear indication for an antiplatelet would provide benefit or harm. Patients were excluded if they had previously been prescribed antiplatelets, which included aspirin and P2Y12 receptor inhibitors.

The study enrolled 25,815 patients with newly diagnosed atrial fibrillation from 1,317 sites in 35 countries. Of those, 3,133 patients were prescribed antiplatelet and oral anticoagulant therapy for the first time and 22,682 were prescribed oral anticoagulants alone.

Patients receiving oral anticoagulants and antiplatelets had a higher prevalence of coronary artery disease, acute coronary syndrome, and stroke. But 1,743 (56%) patients prescribed both drugs did not have coronary artery disease or peripheral artery disease.

Prof Fox said: "More than half of patients prescribed both drugs did not have coronary artery disease or peripheral artery disease, suggesting that they did not have a clear indication for antiplatelet therapy."

Patients were monitored for a minimum of one year. Compared with oral anticoagulation alone, combined treatment with oral anticoagulation and antiplatelet therapy was independently associated with increased risks of major bleeding (hazard ratio [HR] 1.45, 95% confidence interval [CI] 0.94–2.23), all-cause death (HR 1.31, 95% CI 1.05–1.62), and stroke (HR 1.60, 95% CI 1.08–2.35).

Coronary artery disease

Associations between treatment type and outcomes were examined in patients with an indication for antiplatelet therapy – with coronary artery disease or peripheral artery disease – and those without. Combined treatment, compared with oral anticoagulation alone, was independently associated with increased risks of all-cause death (HR 1.37, 95% CI 1.02–1.85) and stroke (HR 1.65, 95% CI 1.02–2.65) in patients without an indication for antiplatelets, but was not harmful in those with an indication.

Prof Fox concluded: "Combined oral anticoagulant and antiplatelet therapy was harmful in patients without an indication for antiplatelets. In those with an indication, it was not harmful but there did not appear to be any benefit. The results question the use of combined treatment in any patient with atrial fibrillation, but particularly in those without an indication for antiplatelets."

The results applied only to patients on full dose anticoagulation. "Patients with atrial fibrillation yet neither coronary artery disease nor other forms of atherosclerosis receiving both medications should consult their doctor," said Prof Fox.

Meanwhile, the ESC Congress took place between 25 – 29 August 2018 in Munich, Germany.

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