Data show bleeding risk from aspirin could outweigh protection from another heart event.
In a finding that suggests less is more, researchers led by the DCRI found that the drugs apixaban and clopidogrel — without aspirin — comprise the safest treatment regimen for certain patients with atrial fibrillation (AF).
The finding, which applies specifically to patients with AF who have had a heart attack and/or are undergoing percutaneous coronary intervention, should reassure clinicians and patients that dropping aspirin results in no significant increase in ischemic events such as heart attacks, strokes and blood clots.
The researchers presented data from the large study, known as AUGUSTUS, on March 17 at the American College of Cardiology annual meeting. The research was also simultaneously published by The New England Journal of Medicine.
“We have a lot of studies on antithrombotic drugs in patients with coronary artery disease and similarly in patients with AF, but few studies in patients with both conditions,” said cardiologist Renato D. Lopes, MD, PhD, principal investigator for the trial and a member of the DCRI.
“The reality is that doctors and patients have a challenge in treating these patients without causing bleeding,” Lopes said. “The results of this trial give us an opportunity to better understand how to best treat them.”
Atrial fibrillation is the most common heart arrhythmia in clinical practice. Around a third of patients with AF also have coronary artery disease and might be taking as many as three different blood thinners to prevent heart attack and stroke. But taking multiple blood thinners increases the risk of uncontrolled bleeding.
Findings from the 4,600-person trial suggest patients double their bleeding risk by adding aspirin to blood thinners without any obvious reduction in risk for heart attack or stroke.
The trial used a factorial design to determine which combinations of antiplatelet and anticoagulant drugs could reduce bleeding in patients who have both coronary artery disease and AF and were already taking an anti-platelet drug such as clopidogrel.
Patients were randomly assigned to add the newer anticoagulant drug apixaban, or a vitamin-K antagonist (VKA) such as warfarin; patients were additionally randomized to take aspirin or a placebo as part of the regimen.
Comparing patients who used apixaban to those who used a VKA, the researchers found that apixaban reduced bleeding by 31 percent and cut death or hospitalizations by 17 percent. There was no difference between apixaban and a VKA to prevent a subsequent major coronary event such as a heart attack.
In the double-blinded segment of the trial that randomized patients to receive either aspirin or a placebo in addition to their other antiplatelet and anticoagulant regimen, the data suggest adding aspirin might do these patients more harm than good, Lopes said.
People who added aspirin had similar rates of death and hospitalization and heart attack compared to patients who received a placebo, Lopes said, but faced almost double the risk of bleeding.
“Patients who got aspirin actually ended up having about an 89 percent increase in major bleeds or clinically relevant non-major bleeds,” Lopes said. “By not giving aspirin, the reduction in bleeds was about 47 percent.”
The data did suggest that although a placebo reduced bleeding risk, more patients experienced ischemic events such as stent thrombosis, myocardial infarction and urgent revascularization. But these findings were not statistically significant and the study was not designed to fully evaluate each specific risk.
“In AUGUSTUS, we identified two effective independent strategies to substantially reduce bleeding, using apixaban rather than a VKA and stopping aspirin, which adds to a growing body of evidence on how to best treat these high-risk and complicated patients,” said cardiologist John H. Alexander, MD, chair of the trial’s executive committee and a member of the DCRI. “While there might be some increased risk of thrombotic events, these are rare compared to the large reductions we saw in bleeding.”
In addition to Lopes, study collaborators included Gretchen Heizer, Ronald Aronson, Amit N. Vora, Tyler Massaro, Roxana Mehran, Shaun G. Goodman, Stephan Windecker, Harald Darius, Jia Li, Oleg Averkov, María Cecilia Bahit, Otavio Berwanger, Andrzej Budaj, Ziad Hijazi, Alexander Parkhomenko, Peter Sinnaeve, Robert F. Storey, Holger Thiele, Dragos Vinereanu, Christopher B. Granger, John H. Alexander and others.
The trial was funded by Bristol-Myers Squibb and Pfizer, Inc., which market the drugs studied. Authors provided individual statements with financial disclosures and potential conflicts of interest.