Oral anticoagulants plus antiplatelets associated with poor outcome in atrial fibrillation

Combined oral anticoagulant and antiplatelet therapy is associated with a worse prognosis than anticoagulation alone in newly diagnosed atrial fibrillation patients without a clear indication for antiplatelets, according to late breaking results from the GARFIELD-AF registry presented today at ESC Congress 2018.

Professor Keith Fox, principal investigator, University of Edinburgh, UK, said: "These findings challenge the use of combined oral anticoagulant and antiplatelet therapy in patients with atrial fibrillation, especially those without an indication for antiplatelet therapy."

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.

Nearly all patients diagnosed with atrial fibrillation should be started on oral anticoagulation to prevent stroke. Adding an antiplatelet increases the risk of bleeding and is 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.

This analysis of the GARFIELD-AF registry3 investigated whether adding an antiplatelet to oral anticoagulation therapy in those without a clear indication for an antiplatelet would provide an overall 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. However, 1,743 (56%) patients prescribed both drugs did not have coronary artery disease or peripheral artery disease.

Professor 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 followed-up for a minimum of 12 months. Compared to 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).

Associations between treatment type and outcomes were then examined in patients with an indication for antiplatelet therapy (with coronary artery disease or peripheral artery disease) and those without (no coronary artery disease or peripheral artery disease). Compared to oral anticoagulation alone, combined treatment 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.

Professor Fox said: "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."

Professor Fox noted that the findings only apply to full dose anticoagulation. He added: "Patients with atrial fibrillation yet neither coronary artery disease nor other forms of atherosclerosis receiving both medications should consult their doctor."