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PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.
When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).
"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.
"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.
Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.
Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).
In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.
"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.
Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.
"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).
"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.
"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."
ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.
Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.
The ARISTOTLE results hit the trifecta, winning on efficacy, safety, and mortality.
The results achieved what everyone has been striving for: to reduce strokes, bleeding, and mortality in atrial fibrillation (AF) patients, compared with the standard drug for stroke protection, warfarin. There are now two large, randomized, controlled trials that show the benefit of apixaban versus warfarin, both ARISTOTLE and AVERROES, which compared apixaban and aspirin in AF patients who were ineligible for or who had failed warfarin treatment.
Do these data give apixaban an edge over the other two new oral anticoagulants, dabigatran and rivaroxaban? That is a question that many people will ask and debate. With the data available now, apixaban looks pretty good. Apixaban’s significant reduction of mortality in the ARISTOTLE results is a key end point. Physicians, patients, and third-party payers may prefer to go with the agent that was proven to reduce all-cause mortality. Neither dabigatran nor rivaroxaban produced a significant survival benefit in their respective pivotal trials, although dabigatran came very close at the 150 mg b.i.d. dosage. I think people will gravitate to the ARISTOTLE results because the study was large, was well conducted, and had a very vigorous design.
But other factors will also come into play. Rivaroxaban offers once-daily dosing. And there is the issue of cost, which has cropped up for dabigatran, the only one of the new alternatives to warfarin for patients with AF currently on the U.S. market. I have seen limited uptake of dabigatran since its Food and Drug Administration approval for AF patients last October because of its cost, and because of the relatively high rate of gastrointestinal adverse effects it can cause.
Physicians want their reliance on warfarin to fade away because of the drug’s many limitations. But it is also familiar and cheap, and in a good warfarin clinic and with good patient compliance it works pretty well and is difficult to beat. With warfarin monitoring you know your patient’s anticoagulant state. Warfarin clinics won’t be shutting down any time soon, but all three of the new anticoagulants – dabigatran, rivaroxaban, and apixaban – beat warfarin on the important end point of reducing intracranial bleeds.
If a patient is doing well on warfarin it’s attractive to not rock the boat and change things. But there seems to be a real benefit from apixaban that holds up among the various subgroups examined. If I thought a patient would be compliant and cost was not an issue then I would consider switching even patients who are well maintained on warfarin to apixaban because the data look so strong.
Dr. Deepak L. Bhatt is chief of cardiology at VA Boston Health System and is a cardiologist at Brigham and Women’s Hospital in Boston. He has received research grants from Bristol-Myers Squibb and several other drug and device companies, and has served on the steering committee for the APPRAISE-2 trial of apixaban and on the executive committee for the ATLAS-2 trial of rivaroxaban.
The ARISTOTLE results hit the trifecta, winning on efficacy, safety, and mortality.
The results achieved what everyone has been striving for: to reduce strokes, bleeding, and mortality in atrial fibrillation (AF) patients, compared with the standard drug for stroke protection, warfarin. There are now two large, randomized, controlled trials that show the benefit of apixaban versus warfarin, both ARISTOTLE and AVERROES, which compared apixaban and aspirin in AF patients who were ineligible for or who had failed warfarin treatment.
Do these data give apixaban an edge over the other two new oral anticoagulants, dabigatran and rivaroxaban? That is a question that many people will ask and debate. With the data available now, apixaban looks pretty good. Apixaban’s significant reduction of mortality in the ARISTOTLE results is a key end point. Physicians, patients, and third-party payers may prefer to go with the agent that was proven to reduce all-cause mortality. Neither dabigatran nor rivaroxaban produced a significant survival benefit in their respective pivotal trials, although dabigatran came very close at the 150 mg b.i.d. dosage. I think people will gravitate to the ARISTOTLE results because the study was large, was well conducted, and had a very vigorous design.
But other factors will also come into play. Rivaroxaban offers once-daily dosing. And there is the issue of cost, which has cropped up for dabigatran, the only one of the new alternatives to warfarin for patients with AF currently on the U.S. market. I have seen limited uptake of dabigatran since its Food and Drug Administration approval for AF patients last October because of its cost, and because of the relatively high rate of gastrointestinal adverse effects it can cause.
Physicians want their reliance on warfarin to fade away because of the drug’s many limitations. But it is also familiar and cheap, and in a good warfarin clinic and with good patient compliance it works pretty well and is difficult to beat. With warfarin monitoring you know your patient’s anticoagulant state. Warfarin clinics won’t be shutting down any time soon, but all three of the new anticoagulants – dabigatran, rivaroxaban, and apixaban – beat warfarin on the important end point of reducing intracranial bleeds.
If a patient is doing well on warfarin it’s attractive to not rock the boat and change things. But there seems to be a real benefit from apixaban that holds up among the various subgroups examined. If I thought a patient would be compliant and cost was not an issue then I would consider switching even patients who are well maintained on warfarin to apixaban because the data look so strong.
Dr. Deepak L. Bhatt is chief of cardiology at VA Boston Health System and is a cardiologist at Brigham and Women’s Hospital in Boston. He has received research grants from Bristol-Myers Squibb and several other drug and device companies, and has served on the steering committee for the APPRAISE-2 trial of apixaban and on the executive committee for the ATLAS-2 trial of rivaroxaban.
The ARISTOTLE results hit the trifecta, winning on efficacy, safety, and mortality.
The results achieved what everyone has been striving for: to reduce strokes, bleeding, and mortality in atrial fibrillation (AF) patients, compared with the standard drug for stroke protection, warfarin. There are now two large, randomized, controlled trials that show the benefit of apixaban versus warfarin, both ARISTOTLE and AVERROES, which compared apixaban and aspirin in AF patients who were ineligible for or who had failed warfarin treatment.
Do these data give apixaban an edge over the other two new oral anticoagulants, dabigatran and rivaroxaban? That is a question that many people will ask and debate. With the data available now, apixaban looks pretty good. Apixaban’s significant reduction of mortality in the ARISTOTLE results is a key end point. Physicians, patients, and third-party payers may prefer to go with the agent that was proven to reduce all-cause mortality. Neither dabigatran nor rivaroxaban produced a significant survival benefit in their respective pivotal trials, although dabigatran came very close at the 150 mg b.i.d. dosage. I think people will gravitate to the ARISTOTLE results because the study was large, was well conducted, and had a very vigorous design.
But other factors will also come into play. Rivaroxaban offers once-daily dosing. And there is the issue of cost, which has cropped up for dabigatran, the only one of the new alternatives to warfarin for patients with AF currently on the U.S. market. I have seen limited uptake of dabigatran since its Food and Drug Administration approval for AF patients last October because of its cost, and because of the relatively high rate of gastrointestinal adverse effects it can cause.
Physicians want their reliance on warfarin to fade away because of the drug’s many limitations. But it is also familiar and cheap, and in a good warfarin clinic and with good patient compliance it works pretty well and is difficult to beat. With warfarin monitoring you know your patient’s anticoagulant state. Warfarin clinics won’t be shutting down any time soon, but all three of the new anticoagulants – dabigatran, rivaroxaban, and apixaban – beat warfarin on the important end point of reducing intracranial bleeds.
If a patient is doing well on warfarin it’s attractive to not rock the boat and change things. But there seems to be a real benefit from apixaban that holds up among the various subgroups examined. If I thought a patient would be compliant and cost was not an issue then I would consider switching even patients who are well maintained on warfarin to apixaban because the data look so strong.
Dr. Deepak L. Bhatt is chief of cardiology at VA Boston Health System and is a cardiologist at Brigham and Women’s Hospital in Boston. He has received research grants from Bristol-Myers Squibb and several other drug and device companies, and has served on the steering committee for the APPRAISE-2 trial of apixaban and on the executive committee for the ATLAS-2 trial of rivaroxaban.
PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.
When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).
"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.
"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.
Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.
Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).
In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.
"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.
Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.
"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).
"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.
"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."
ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.
Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.
PARIS – The growing list of oral anticoagulant drugs jockeying to replace warfarin as the go-to agent for stroke prevention in patients with atrial fibrillation added a new candidate, apixaban, that appeared to immediately take the lead on the strength of strikingly impressive results in an 18,000-patient trial.
When matched against warfarin, atrial fibrillation (AF) patients treated with apixaban (Bristol-Myers Squibb, Pfizer) had significantly lower rates of stroke and systemic embolism, major bleeding complication, and overall mortality, compared with patients randomized to warfarin during a median follow-up of 1.8 years, Dr. Christopher B. Granger reported Aug. 28 at the annual congress of the European Society of Cardiology, and in a published article that concurrently appeared online (N. Engl. J. Med. 2011 Aug. 28 [10.1056/NEJMoa1107039]).
"Treatment with apixaban as compared with warfarin in patients with AF and at least one additional risk factor for stroke reduces stroke and systemic embolism by [a relative] 21%, reduces major bleeding by [a relative] 31%, and reduces mortality by [a relative] 11%," all statistically significant differences, reported Dr. Granger, director of the cardiac care unit at Duke University in Durham, N.C.
"I view the study as a home run. It is incredibly important, and it put another stake in the heart of warfarin in the management of atrial fibrillation to prevent stroke," commented Dr. Ralph Brindis, senior adviser for cardiovascular diseases at Northern California Kaiser.
Apixaban’s accomplishment in significantly surpassing warfarin’s performance for the trio of stroke prevention, bleeding safety, and overall mortality in its pivotal trial, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, appeared to vault it ahead of dabigatran (Pradaxa, Boehringer Ingelheim), which received Food and Drug Administration approval for stroke prevention in AF patients last October, and the still-investigational agent rivaroxaban (Xarelto, Janssen), which the FDA is currently reviewing for a similar AF indication.
Neither dabigatran nor rivaroxaban could match apixaban’s performance in their respective pivotal AF trials: the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study that matched dabigatran against warfarin in 18,113 randomized patients (N. Engl. J. Med. 2009;361:1139-51), and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study that pitted rivaroxaban against warfarin in 14,264 randomized patients (N. Engl. J. Med. 2011 Aug. 10 [10.1056/NEJMoa1009638]).
In RE-LY, which tested two different dabigatran dosages, the 110-mg/b.i.d. dosage produced stroke and systemic embolism prevention that was noninferior to warfarin while leading to a statistically significant reduction in major bleeds, and the 150-mg/b.i.d. dosage (the primary dosage approved by the FDA) produced a statically significant reduction in strokes and systemic embolisms compared with warfarin while being noninferior to the comparator for major bleeds. In ROCKET-AF, once-daily treatment with rivaroxaban proved noninferior to warfarin for both the primary efficacy end point of fewer strokes and systemic embolisms and the safety end point of major bleeds.
"We think we hit the sweet spot in terms of the [apixaban] dose" in ARISTOTLE, said Dr. Granger, and although he and other experts warned against the pitfalls of cross-trial comparisons, many also acknowledged that mental calculations comparing the demonstrated pros and cons of each of these three new drugs are inevitable once all three drugs become routinely available.
Results from a study directly comparing two or all three of these drugs won’t be available soon, leaving it to clinicians to take into account not only the efficacy and safety performance of the three agents in these studies but other considerations as well, such as their prices, dosing convenience, adverse effects, and individual patient reactions.
"Apixaban has a certain edge because of its safety; [it] reduced all types of bleeding and had impressive tolerability," said Dr. Lars Wallentin, professor and head of cardiology research at Uppsala University in Sweden, and a coinvestigator in both the ARISTOTLE and RE-LY trials. Apixaban also has the attraction of having another major stroke-prevention in AF under its belt, the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study, which randomized 5,599 patients (N. Engl. J. Med. 2011;364:806-17).
"We have two [apixaban] trials [in] a large program, showing this safety. In AVERROES the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Wallentin said in an interview.
"I think it will be very competitive" among the three new drugs, said Dr. Michael D. Ezekowitz, professor of medicine at Thomas Jefferson University in Philadelphia and a lead investigator of the RE-LY trial. "That’s what we want; multiple agents competing, each one finding their niche in the huge field of atrial fibrillation treatment. The companies [that make these new drugs] will compete at multiple levels."
ARISTOTLE’s results showed that among patients randomized to apixaban, the rate of the primary stroke and systemic end point during follow-up was 1.27%, major bleeds occurred in 2.13%, the rate of death from any cause was 3.52%, and 0.24% of patients developed a hemorrhagic stroke. In patients randomized to warfarin, strokes or embolisms occurred in 1.60%, major bleeds in 3.09%, all-cause death in 3.94%, and hemorrhagic stroke in 0.47%. All of the differences between the two treatment groups were statistically significant. Over the median 1.8-year follow-up of the study, treatment of 1,000 patients with apixaban prevented on average six strokes (four hemorrhagic and two ischemic or unknown type), 15 major bleeds, and eight deaths compared with patients treated with warfarin.
Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Patients treated with the investigational factor Xa inhibitor apixaban had significantly fewer strokes and systemic embolisms, major bleeds, and mortality compared with patients treated with warfarin.
Data Source: The ARISTOTLE trial, which randomized 18,201 patients with atrial fibrillation and at least one other stroke risk factor.
Disclosures: Dr. Granger said that he has received grants and consultant fees from numerous pharmaceutical companies, including Boehringer Ingelheim. Dr. Brindis said that he had no disclosures. Dr. Wallentin has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Roche, and Merck-Schering Plough, and has been an advisor or consultant to Portola, CSL Behring, Evola, Athera, and Regado. Dr. Ezekowitz said that he has been a consultant to and has received grants from numerous companies including Boehringer Ingelheim. He was also a co–principal investigator for the RE-LY study, on the executive committee of Engage AF, and lead investigator for betrixaban.