New ACC Pathway in Atrial Fibrillation Calls for Limiting Aspirin

The American College of Cardiology provides new guidance on the best therapy to prevent blood clots for patients with atherosclerotic cardiovascular disease who also have atrial fibrillation or venous thromboembolism and require an anticoagulant.

Cardiologists should stop routinely prescribing a 3-drug antithrombotic regimen to patients needing both anticoagulant and antiplatelet therapy because its inclusion of aspirin significantly increases the risk of major bleeding, according to new guidance from the American College of Cardiology (ACC).

The ACC now “strongly recommends” a “dual therapy”—an anticoagulant and an antiplatelet agent known as a P2y12 inhibitor—in most circumstances, according to a statement. In cases where the regimen commonly known as “triple therapy” is appropriate for trying to avoid blood clots, cardiologists should discontinue the aspirin as soon as possible—generally no more than 30 days. 

The guidance was published Friday in a new Expert Consensus Decision Pathway (ECDP) document in the Journal of the American College of Cardiology. The new ECDP, led by chairman Dharam J. Kumbhani, MD, SM, FACC, and Vice Chair Christopher P. Cannon, MD, FACC, acknowledges that choosing the best antithrombotic regimen can be challenging for clinicians treating patients with atherosclerotic cardiovascular disease who simultaneously have atrial fibrillation (AFib) or venous thromboembolism (VTE) patients and require an anticoagulant. 

However, review of newer research suggests that avoiding aspirin in such patients is usually a safer route, decreasing the chances of major bleeding. The risk of death is up to 5 times higher after an acute coronary syndrome when major bleeding occurs.

Much of the discussion in the new ECDP was developed based on ACC-sponsored Heart House Roundtables held in Washington, DC, in 2016 and 2017. Additional evidence from clinical trials and meta-analyses also was used. Data for patients with VTE is limited, the authors said, so they had to extrapolate from trials in patients with AFib for many of the ECDP recommendations. The ECDP explores four different clinical scenarios providing more detailed guidance.

Clinicians had been relying on older trials that suggested an oral anticoagulant alone was not optimal for those undergoing percutaneous coronary intervention (PCI). Similarly, dual antiplatelet therapy was not optimal with those with AFib or VTE.

But the risks with triple therapy are too high to continue using in most cases, the authors wrote. Estimates are that adding a single antiplatelet therapy to an oral coagulant increase the risk of bleeding from 20-60%. In contrast, the addition of two antiplatelet agents increases the risk two- or threefold.

“The risk of major bleeding with major antithrombotic therapy can be as high as 2.2% at 1 month and 4% to 12% at 1 year,” the authors wrote.

Approximately 1 in 4 individuals develop AFib during their lifetime, increasing the risk of stroke by 4 to 5 times, accounting for 15% to 20% of ischemic strokes. Treatment with an oral anticoagulant is associated with a much lower stroke risk.

Coronary artery disease is common in patients with AFib. About 25% to 35% of such patients have both conditions, which have common risk factors such as obesity, hypertension, and type 2 diabetes (T2D).

VTE, including deep venous thrombosis and pulmonary embolism, is common as well (1 to 2 per 1000 person-years). It is usually treated with anticoagulants. Given the apparent common risk factors for VTE and coronary artery disease, antiplatelet therapy is often used in treatment. 

The routine use of a second antiplatelet agent—aspirin—is what needs to change, the authors wrote. One approach has been the use of triple therapy, with shorter duration of a P2 y12 inhibitor such as clopidogrel. But in the ISAR-TRIPLE trial (Triple Therapy in Patients on Oral Anticoagulation after Drug Eluting Stent Implementation), there was no reduction in major bleeding (hazard ratio 1.35; 95% CI 0.64 to 2.84).

However, multiple trials have been performed on use of triple therapy where aspirin was discontinued after discharge. Major bleeding was significantly less.


Khumbani DJ, Cannon, CP, Beavers, CJ, et al. 2020 ACC Expert Consensus Decision Pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease. J Am Coll Cardiol. Published online December 18, 2020. doi:10.1016/j.jacc.2020.09.011