Effects of Antiplatelet Therapy on Clinical Outcomes in AF Treated With Anticoagulation

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Researchers conducted a meta-analysis to assess the association between antiplatelet therapy with or without anticoagulant use and outcomes including stroke, intracranial hemorrhage, major bleeding, MI, and death in patients with atrial fibrillation.

In patients with atrial fibrillation, antiplatelet therapy was found to be associated with a reduction in myocardial infarction (MI), an increase in bleeding, and no effect on mortality while showing a slight reduction in stroke, according to research published in European Heart Journal – Cardiovascular Pharmacotherapy.

Through this systematic review and meta-analysis of previously conducted trials on antiplatelet therapy with or without anticoagulation (N=18 selected of 5446 drawn from 3 databases), researchers investigated various outcomes (stroke, intracranial hemorrhage, major bleeding, MI, death) in patients with atrial fibrillation. Trials, released beginning in 1989 and ending in 2019, were selected only if patients were on oral aspirin or P2Y12 inhibitor therapy for at least 12 weeks and were compared with participants in a control group.

In patients who were on antiplatelet therapy but not on anticoagulants, study authors observed a modest reduction in stroke (486 events/6165 patients vs 621 events/6061 patients; risk ratio [RR], 0.77; 95% CI, 0.69-0.86; I2 =0%). On the other hand, in patients who were receiving anticoagulants and antiplatelets, there was a signal for an increased risk in all-cause stroke associated with antiplatelets (97 events/4608 patients vs 72 events/4684 patients; RR, 1.33; 95% CI, 0.98-1.79; I2=0%; P <.001).

Of 15 trials that evaluated major bleeding, 837 bleeding events were recorded in 20,898 patients. Antiplatelet use caused a significant increase in major bleeding (509 events/10,402 patients vs 328 events/10,496 patients; RR, 1.54; 95% CI, 1.35-1.77; interaction, P =.94).

Overall, 172 intracranial hemorrhage events were recorded in 20,453 patients. Study authors observed that antiplatelet use was associated with a significant increase in intracranial hemorrhage (107 events/10,221 patients vs 65 events/10,232 patients; RR, 1.64; 95% CI, 1.20-2.24) with or without anticoagulant therapy (interaction, P =.36).

Antiplatelet therapy was accompanied by a reduction in ischemic stroke in patients not taking anticoagulants (RR, 0.72; 95% CI, 0.63-0.82, I2=0%). Study authors noted a corresponding signal for harm in patients using antiplatelets with background oral anticoagulants (RR, 1.36; 95% CI, 0.96-1.94; I2 =0%).

Of 13 studies reporting MI data, 461 MI events were recorded in 19,430 patients. There was a moderate reduction in MI associated with the use of antiplatelets without regard to anticoagulant therapy (201 events/9679 patients vs 260 events/9751 patients; RR, 0.79; 95% CI, 0.65-0.94; interaction, P =.82)

Heterogeneity was not significant between groups or studies for intracranial hemorrhage, ischemic stroke, and MI.

Overall, 15 studies reported 2432 deaths out of 20,586 patients. Mortality did not seem to be affected by antiplatelet use with comparable incidences between groups (1221 events/10,299 patients vs 1211 events/10,287 patients; RR, 1.02; 95% CI, 0.89-1.17; interaction, P =.23) independent of anticoagulant therapy.

There was moderate heterogeneity overall (I2 =29%) and significant heterogeneity (I2 =52%) in patients on anticoagulant background therapy; the association was later eliminated via sensitivity analysis conducted post hoc by excluding one trial “prematurely stopped for an excess in mortality.”

Researchers also found most of the trials selected to have “low risk of bias.” The quality of evidence (of increase observed in all-cause, ischemic stroke in patients using anticoagulants) was designated as moderate and the quality of evidence was designated as high for the other outcomes based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.

A limitation acknowledged by the authors includes the lack of direct access to patient data and differing comorbid cardiovascular conditions aside from atrial fibrillation.

For patients with atrial fibrillation, researchers found that antiplatelet therapy was associated with an increase in bleeding and intracranial hemorrhage, a reduction in MI, and no effect on mortality irrespective of anticoagulation. However, a signal for harm was observed when used in conjunction with anticoagulants. On the other hand, antiplatelet therapy without anticoagulants showed a slight reduction in stroke.

The authors state that, “the association with a moderate reduction in myocardial infarction with antiplatelets, also independent of background oral anticoagulation, highlights the clinical challenge of balancing the risks of thromboembolism and major hemorrhage in patients who require antithrombotic therapy.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures


Benz AP, Johansson I, Dewilde WJM, et al. Antiplatelet therapy in patients with atrial fibrillation: a systematic review and meta-analysis of randomized trials. Eur Heart J Cardiovasc Pharmacother Published online June 17, 2021. doi:10.1093/ehjcvp/pvab044