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MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.
"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.
The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).
But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.
"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).
"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.
The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).
"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.
In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."
Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."
The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m2 or less.
The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.
In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.
The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.
Renal dysfunction is highly prevalent in patients with atrial fibrillation and is associated with both stroke and bleeding risk. In ARISTOTLE, the overall findings of the trial are consistent with the outcomes seen in patients with moderate renal dysfunction, with an estimated glomerular filtration rate (eGFR) of less than 50 mL/min per 1.73 m2.
The ARISTOTLE results showed that the rate of ischemic stroke was twofold higher, the rate of major bleeds was threefold higher, and the mortality rate was threefold higher among patients with an eGFR of 50 mL/min per 1.73 m2 or less compared with patients with an eGFR of greater than 80 mL/min per 1.73 m2.
The benefit over warfarin of reduced bleeding appears to be more marked in patients with moderate renal dysfunction. These patients received a reduced apixaban dosage, 2.5 mg b.i.d. instead of the full dosage of 5 mg b.i.d., but results of a sensitivity analysis by the researchers suggested that this reduced dosage was not the key factor producing the reduced rate of major bleeds.
In my view, apixaban provides a treatment option and advantages over warfarin in atrial fibrillation patients with moderate renal dysfunction, a group of patients who currently receive suboptimal management.
Keith A.A. Fox, M.D., is professor of cardiology at the University of Edinburgh. He said that he has received grant funding and honoraria from Sanofi, Lilly, Bayer/Johnson & Johnson, Astra Zeneca, and Boehringer Ingelheim. He made these comments as designated discussant for the report by Dr. Hohnloser.
Renal dysfunction is highly prevalent in patients with atrial fibrillation and is associated with both stroke and bleeding risk. In ARISTOTLE, the overall findings of the trial are consistent with the outcomes seen in patients with moderate renal dysfunction, with an estimated glomerular filtration rate (eGFR) of less than 50 mL/min per 1.73 m2.
The ARISTOTLE results showed that the rate of ischemic stroke was twofold higher, the rate of major bleeds was threefold higher, and the mortality rate was threefold higher among patients with an eGFR of 50 mL/min per 1.73 m2 or less compared with patients with an eGFR of greater than 80 mL/min per 1.73 m2.
The benefit over warfarin of reduced bleeding appears to be more marked in patients with moderate renal dysfunction. These patients received a reduced apixaban dosage, 2.5 mg b.i.d. instead of the full dosage of 5 mg b.i.d., but results of a sensitivity analysis by the researchers suggested that this reduced dosage was not the key factor producing the reduced rate of major bleeds.
In my view, apixaban provides a treatment option and advantages over warfarin in atrial fibrillation patients with moderate renal dysfunction, a group of patients who currently receive suboptimal management.
Keith A.A. Fox, M.D., is professor of cardiology at the University of Edinburgh. He said that he has received grant funding and honoraria from Sanofi, Lilly, Bayer/Johnson & Johnson, Astra Zeneca, and Boehringer Ingelheim. He made these comments as designated discussant for the report by Dr. Hohnloser.
Renal dysfunction is highly prevalent in patients with atrial fibrillation and is associated with both stroke and bleeding risk. In ARISTOTLE, the overall findings of the trial are consistent with the outcomes seen in patients with moderate renal dysfunction, with an estimated glomerular filtration rate (eGFR) of less than 50 mL/min per 1.73 m2.
The ARISTOTLE results showed that the rate of ischemic stroke was twofold higher, the rate of major bleeds was threefold higher, and the mortality rate was threefold higher among patients with an eGFR of 50 mL/min per 1.73 m2 or less compared with patients with an eGFR of greater than 80 mL/min per 1.73 m2.
The benefit over warfarin of reduced bleeding appears to be more marked in patients with moderate renal dysfunction. These patients received a reduced apixaban dosage, 2.5 mg b.i.d. instead of the full dosage of 5 mg b.i.d., but results of a sensitivity analysis by the researchers suggested that this reduced dosage was not the key factor producing the reduced rate of major bleeds.
In my view, apixaban provides a treatment option and advantages over warfarin in atrial fibrillation patients with moderate renal dysfunction, a group of patients who currently receive suboptimal management.
Keith A.A. Fox, M.D., is professor of cardiology at the University of Edinburgh. He said that he has received grant funding and honoraria from Sanofi, Lilly, Bayer/Johnson & Johnson, Astra Zeneca, and Boehringer Ingelheim. He made these comments as designated discussant for the report by Dr. Hohnloser.
MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.
"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.
The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).
But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.
"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).
"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.
The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).
"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.
In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."
Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."
The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m2 or less.
The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.
In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.
The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.
MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.
"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.
The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).
But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.
"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).
"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.
The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).
"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.
In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."
Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."
The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m2 or less.
The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.
In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.
The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Among atrial fibrillation patients with renal dysfunction, apixiban produced 35%-52% fewer major bleeding episodes compared with warfarin.
Data Source: A prespecified substudy of ARISTOTLE, a multicenter, randomized trial of 18,201 patients with atrial fibrillation.
Disclosures: The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from sanofi-aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.
