In the Journals

Treatment effect of apixaban consistent regardless of history of falls

Renato Lopes
Renato D. Lopes

In a subanalysis of the ARISTOTLE trial, history of falls had no bearing on the improved safety and efficacy of apixaban vs. warfarin in patients with nonvalvular atrial fibrillation, researchers reported.

Patients who had a history of falling had higher rates of bleeding and death compared with those who did not, but the benefits of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) in reducing stroke and causing less bleeding than warfarin were consistent regardless of history of fall in the prior year, Renato D. Lopes, MD, PhD, MHS, professor of medicine in the division of cardiology at Duke University Medical Center, and colleagues wrote.

As Cardiology Today previously reported, in ARISTOTLE, apixaban was associated with lower risk for stroke/systemic embolism and major bleeding compared with warfarin in patients with nonvalvular AF.

Lopes and colleagues analyzed 16,491 patients from ARISTOTLE to determine whether the treatment effect with apixaban vs. warfarin differed in patients with a history of falls (n = 753; mean age, 75 years; 47% women) vs. patients with no history of falls (n = 15,738; mean age, 70 years; 35% women).

Potential for falls

“If a patient has a prior fall, we know they are more likely to fall again, which could make their risk of bleeding even higher,” Lopes told Cardiology Today. “So, sometimes the risk for falling again can be considered a relative contraindication for an anticoagulant from a physician’s perspective. We know that in patients with atrial fibrillation the use of oral anticoagulation therapy for stroke prevention is one of the key pillars of treatment, but unfortunately the history of falls — and associated increased risk of bleeding — is often pointed out by many physicians as an important reason for not treating these patients with an oral anticoagulant. So, this is a very important subgroup of patients for whom we don’t have a lot of information.”

In addition to age and sex differences, compared with those with no history, those with a history of falls were more likely to have dementia, cerebrovascular disease, diabetes, depression, HF, osteoporosis and fractures, and had higher CHA2DS2-VASc and HAS-BLED scores, Lopes and colleagues wrote.

Compared with patients with no history, patients with a history of falls had elevated risk for major bleeding (adjusted HR = 1.39; 95% CI, 1.05-1.84), intracranial bleeding (aHR = 1.87; 95% CI, 1.02-3.43) and death (aHR = 1.7; 95% CI, 1.36-2.14), but similar rates of stroke/systemic embolism and hemorrhagic stroke, the researchers wrote.

There was no difference in treatment effect of apixaban vs. warfarin stratified by falls vs. no falls for any outcome, including stroke/systemic embolism (P for interaction = .69), major bleeding (P for interaction = .57), major or clinically relevant nonmajor bleeding (P for interaction = .06), any bleeding (P for interaction = .46), CV death (P for interaction = .11) and all-cause death (P for interaction = .63), according to the researchers.

Treatment effect preserved

“We showed that the treatment effect of apixaban vs. warfarin was absolutely preserved,” Lopes told Cardiology Today. “Apixaban was a safer and more efficacious treatment than warfarin regardless if the patient had a prior fall or not.”

Although patients with prior falls “are at higher risk for falling, bleeding or dying, nonetheless, preventing stroke — and, therefore, using an anticoagulant — is in general more important than the risk of bleeding, particularly if we have drugs that can be safer than warfarin,” he said. “It is reassuring to have an option that can put high-risk patients at lower risk of bleeding while keeping the benefit of reducing stroke.” – by Erik Swain

For more information:

Renato D. Lopes, MD, PhD, MHS, can be reached at renato.lopes@duke.edu.

Disclosures: The ARISTOTLE study was funded by Bristol-Myers Squibb and Pfizer. Lopes reports he received research grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer and Sanofi Aventis; he received fees for consulting or other services from Bayer AG, Boehringer Ingelheim and Bristol-Myers Squibb; and he received fees for educational activities or lectures from Pfizer. Please see the study for the other authors’ relevant financial disclosures.

Renato Lopes
Renato D. Lopes

In a subanalysis of the ARISTOTLE trial, history of falls had no bearing on the improved safety and efficacy of apixaban vs. warfarin in patients with nonvalvular atrial fibrillation, researchers reported.

Patients who had a history of falling had higher rates of bleeding and death compared with those who did not, but the benefits of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) in reducing stroke and causing less bleeding than warfarin were consistent regardless of history of fall in the prior year, Renato D. Lopes, MD, PhD, MHS, professor of medicine in the division of cardiology at Duke University Medical Center, and colleagues wrote.

As Cardiology Today previously reported, in ARISTOTLE, apixaban was associated with lower risk for stroke/systemic embolism and major bleeding compared with warfarin in patients with nonvalvular AF.

Lopes and colleagues analyzed 16,491 patients from ARISTOTLE to determine whether the treatment effect with apixaban vs. warfarin differed in patients with a history of falls (n = 753; mean age, 75 years; 47% women) vs. patients with no history of falls (n = 15,738; mean age, 70 years; 35% women).

Potential for falls

“If a patient has a prior fall, we know they are more likely to fall again, which could make their risk of bleeding even higher,” Lopes told Cardiology Today. “So, sometimes the risk for falling again can be considered a relative contraindication for an anticoagulant from a physician’s perspective. We know that in patients with atrial fibrillation the use of oral anticoagulation therapy for stroke prevention is one of the key pillars of treatment, but unfortunately the history of falls — and associated increased risk of bleeding — is often pointed out by many physicians as an important reason for not treating these patients with an oral anticoagulant. So, this is a very important subgroup of patients for whom we don’t have a lot of information.”

In addition to age and sex differences, compared with those with no history, those with a history of falls were more likely to have dementia, cerebrovascular disease, diabetes, depression, HF, osteoporosis and fractures, and had higher CHA2DS2-VASc and HAS-BLED scores, Lopes and colleagues wrote.

Compared with patients with no history, patients with a history of falls had elevated risk for major bleeding (adjusted HR = 1.39; 95% CI, 1.05-1.84), intracranial bleeding (aHR = 1.87; 95% CI, 1.02-3.43) and death (aHR = 1.7; 95% CI, 1.36-2.14), but similar rates of stroke/systemic embolism and hemorrhagic stroke, the researchers wrote.

There was no difference in treatment effect of apixaban vs. warfarin stratified by falls vs. no falls for any outcome, including stroke/systemic embolism (P for interaction = .69), major bleeding (P for interaction = .57), major or clinically relevant nonmajor bleeding (P for interaction = .06), any bleeding (P for interaction = .46), CV death (P for interaction = .11) and all-cause death (P for interaction = .63), according to the researchers.

Treatment effect preserved

“We showed that the treatment effect of apixaban vs. warfarin was absolutely preserved,” Lopes told Cardiology Today. “Apixaban was a safer and more efficacious treatment than warfarin regardless if the patient had a prior fall or not.”

Although patients with prior falls “are at higher risk for falling, bleeding or dying, nonetheless, preventing stroke — and, therefore, using an anticoagulant — is in general more important than the risk of bleeding, particularly if we have drugs that can be safer than warfarin,” he said. “It is reassuring to have an option that can put high-risk patients at lower risk of bleeding while keeping the benefit of reducing stroke.” – by Erik Swain

For more information:

Renato D. Lopes, MD, PhD, MHS, can be reached at renato.lopes@duke.edu.

Disclosures: The ARISTOTLE study was funded by Bristol-Myers Squibb and Pfizer. Lopes reports he received research grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer and Sanofi Aventis; he received fees for consulting or other services from Bayer AG, Boehringer Ingelheim and Bristol-Myers Squibb; and he received fees for educational activities or lectures from Pfizer. Please see the study for the other authors’ relevant financial disclosures.