More than a decade ago, the anticoagulant apixaban, trade name Eliquis, was shown to be superior to aspirin for preventing recurrent stroke in patients with a heart condition called atrial fibrillation.
But a multicenter, phase 3 clinical trial has found that apixaban is no more effective than aspirin at preventing a second stroke in patients diagnosed with a milder, related condition called atrial cardiopathy, according to results reported by researchers at Weill Cornell Medicine, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian. The findings should inform clinical practice for many thousands of stroke patients worldwide.
It is estimated that about one in seven strokes is caused by atrial fibrillation, a common arrhythmia linked to the formation of blood clots in the heart. These clots can trigger strokes by dislodging and blocking arteries that serve the brain. Atrial cardiopathy, a condition in which the heart shows signs of subtle structural and functional abnormalities, is thought by many researchers to be a potential precursor to atrial fibrillation, and also has been linked to blood clots and strokes. Researchers therefore have hypothesized that anticoagulants might also prevent recurrent strokes more effectively than aspirin in patients with atrial cardiopathy, even when they don’t yet show signs of atrial fibrillation.
The new , tested the two treatments in 1,015 such patients at 185 clinical centers in the United States and Canada. It found that the rate of new strokes was the same, whether the patients took apixaban or aspirin.
“It’s not uncommon that a clinician will suspect atrial fibrillation in a patient despite not having a clear indication of it, and will prescribe anticoagulation therapy – but the implication of this study is that this practice isn’t going to be effective,” said the study’s first author Dr. Hooman Kamel, the Helen and Albert Moon Professor of Neurology and vice chair for research in the Department of Neurology, and director of the Clinical and Translational Neuroscience Unit in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine, and a neurologist at NewYork-Presbyterian/Weill Cornell Medical Center.
“We were trying to find the threshold at which anticoagulant therapy becomes more effective than aspirin, and it may be that that threshold is higher and requires clear signs of atrial fibrillation,” said study senior author Dr. Mitchell Elkind, professor of neurology and epidemiology at Columbia University Vagelos College of Physicians and Surgeons and a neurologist at NewYork-Presbyterian/Columbia University Irving Medical Center. Elkind also currently serves as the chief clinical science officer of the American Heart Association.
Stroke has long been one of the top public health burdens and causes of death globally. In the United States alone, there are about , the vast majority caused by blood clots that block arteries in the brain. Many stroke-causing clots arise directly in cerebral arteries, due to atherosclerosis (arterial narrowing and damage from cholesterol plaques). The rest arise in vessels outside the brain.
Stroke-causing clots in atrial fibrillation patients tend to form in the left atrium of the heart. Research over the past decade has suggested that left atrium clots may also arise when a patient has atrial cardiopathy. The condition can be present even in the absence of atrial fibrillation, although atrial fibrillation is often seen at the same time, and the two conditions are suspected to be related.
A highly collaborative clinical trial, known as ARCADIA (AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke), was set up to test the use of anticoagulants in these cases. Each patient in the trial had signs of atrial cardiopathy without apparent atrial fibrillation and had recently experienced a stroke that could not be attributed to atrial fibrillation, cerebral artery atherosclerosis or other causes. Half the patients were assigned to take one daily 81-mg aspirin, the other to daily apixaban.
As is often the case for such large and costly trials, this one provided for an interim “futility analysis” of results, so that the trial could be stopped if there were insufficient statistical evidence of the hypothesized effect. The futility analysis was performed after an average patient follow-up of 1.8 years and showed that there was the same rate of new strokes – 4.4% per year – in each group, indicating no difference between aspirin and apixaban. Thus, the trial was terminated early.
While the study overall yielded an unexpected negative result, the researchers noted that it represents progress for the field.
“It addressed an important question and should now steer physicians away from prescribing anticoagulants for patients like the ones in our study,” Elkind said.
Kamel and Elkind added that the results have prompted plans for new studies to better clarify which patients can benefit from anticoagulant therapy for reducing stroke risk.
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Jim Schnabel is a freelance writer for Weill Cornell Medicine.
