Key Papers on Atrial Fibrillation and Other Sessions From Day 3, ESC 2010
I'm Dr. Melissa Walton-Shirley reporting to you on this third day of the European Society of Cardiology (ESC) meeting in Stockholm. It's Tuesday, August 31. Today's hot studies included ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation), which studied the effect of olmesartan on atrial fibrillation recurrence, EINSTEIN DVT (Oral rivaroxaban vs standard therapy in the initial treatment of symptomatic deep vein thrombosis and long-term prevention of recurrent venous thromboembolism) reporting on oral rivaroxaban, and AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes)[3] looking at the factor Xa inhibitor apixaban in stroke prevention. I'll also briefly discuss DANPACE (The Danish multicenter randomized trial on single lead atrial vs dual chamber pacing in sick sinus syndrome), an analysis of single- vs dual-chamber pacing in sick sinus syndrome and then move on to the prevention trial RESPONSE (Effect of a nurse coordinated prevention program on cardiovascular risk after an acute coronary syndrome) and finally FUTURA OASIS-8 (A randomized trial comparing two regimens of adjunctive intravenous unfractionated heparin during PCI in high-risk patients with non-ST-segment elevation acute coronary syndrome treated with fondaparinux) comparing fondaparinux with 2 different unfractionated heparin (UFH) regimens and non-ST-segment elevation acute coronary syndrome (non-STE-ACS).
Let's get started with the ANTIPAF study presented by Dr. Andreas Goette of Germany. This was the first prospective trial that examined the impact of an angiotensin receptor blocker (ARB), specifically olmesartan, on the incidence of atrial fibrillation. Patients who were taking beta-blockers were chosen to participate in the study to remove the question of the impact of that therapy on atrial fibrillation recurrence. The patients were monitored with intermittent home telemetry monitoring with the primary endpoint being that of the percentage of days with documented episodes of atrial fibrillation over 12 months.
Four hundred twenty-five patients submitted 87,181 electrocardiograms for analysis. The unfortunate result was that there was no impact of the ARB olmesartan utilization on atrial fibrillation recurrence rate. This was an important negative trial in the quest to find the right combination for prophylaxis against atrial fibrillation recurrence.
EINSTEIN DVT came to us by way of Dr. Harry Büller of Amsterdam, who presented this trial pitting rivaroxaban, an oral direct factor Xa inhibitor, against standard low-molecular-weight heparin and coumadin or acenocoumarol for treatment of deep venous thrombosis (DVT), but not pulmonary embolism. The treatment arm was a single drug approach from the outset, but was an open-label randomized study powered to evaluate noninferiority to standard care, which it well demonstrated with a P value of less than .0001.
The dosing regimen utilized was 15 mg twice daily for 3 weeks followed by 20 mg once daily for 3, 6, or 12 months depending on the physician's assessment. The primary endpoint of this trial was recurrent DVT with a secondary endpoint of a composite of major and clinically relevant non-major bleeding. The presenter was careful to note that there were no trends of abnormal liver signals noted in this trial.
Rivaroxaban is marketed outside of the United States under the name of Xarelto® and is so far approved for the prophylaxis of DVT. But according to Bloomberg with a second verification from the company they will be seeking regulatory approval for the prevention of embolic stroke in atrial fibrillation by the end of 2010.
Now for the AVERROES study presented by Dr. Stuart Connelly of Ontario. This was a phase 3 trial of yet another factor Xa inhibitor, apixaban, which has already been investigated for the prevention of DVT following orthopaedic surgery. Five thousand six hundred patients with atrial fibrillation were enrolled with a mean age of 70 years and these were patients who were not thought to be optimal candidates for a vitamin K antagonist. The characteristics of those cohorts included simple refusal to take warfarin, increased risk for hemorrhage, or difficult-to-control international normalized ratios (INRs) and included those with intermediate stroke risk as well.
The study drug was compared with aspirin alone. The results were that the primary outcome of stroke or systemic embolization was 3.9% per year with aspirin alone, but only 1.7% on apixaban. The rate of major hemorrhage was 1.4% per year on aspirin and 1.6% on apixaban, but with a nonsignificant P value of 0.33. The rate of hemorrhagic stroke was identical and there was no evidence of hepatotoxicity.
The presenter concluded that it appears that apixaban will be an excellent treatment for many patients with atrial fibrillation who are unsuitable for or are unwilling to take warfarin. These findings will reduce the burden of stroke in society. We were unable to verify when the US Food and Drug Administration approval process will start because the company stated there are no regulatory information pieces to report at this time.
DANPACE was a trial presented by Dr. Jens Nielsen of Denmark and sought to answer the question as to whether single-chamber or dual-chamber pacing was best in the treatment of sick sinus syndrome. Although there are no differences in survival between single-chamber atrial rate-adaptive pacing (AAIR) and dual-chamber rate responsive (DDDR) pacing, the risk for reoperation was double with AAIR pacing and a paroxysmal atrial fibrillation incidence was increased by 27% in single lead pacing.
The final recommendation stemming from this trial was that AAIR pacing should not be used and even more specifically that DDDR pacing with an atrioventricular interval of less than 220 milliseconds is the preferred pacing mode for sick sinus syndrome.
The RESPONSE trial, presented by Dr. Ron Peters of The Netherlands, was an interesting look at secondary prevention where outpatient nursing follow-up was coordinated for patients who had been hospitalized for heart attack or impending heart attack. The trial design included regular nursing follow-up for 754 patients randomized to either usual care alone or usual care plus 6 month nursing interventions that included 4 extra visits to an outpatient clinic for advice on food choices, exercise, smoking, and weight control.
The nurses monitored blood pressure, cholesterol, blood sugar, and preventative medications. Six months after the last nursing visit, which was the 12-month mark following enrollment, the primary endpoint was measured. The nurses were able to achieve a reduction in the risk for death by 17%, but failed in the categories of smoking cessation and weight loss. They did achieve improvements in blood pressure control and low-density lipoprotein cholesterol. It was noted that more than 93% of patients attended all visits, a very impressive display of visit compliance. When asked following the presentation regarding smoking cessation training, there were no cessation medications given and the nurses received no special training in that area.
Finally we have FUTURA OASIS-8, a randomized trial presented by Dr. Jolly of Ontario. The presentation began by referencing OASIS-5, which had previously led to a decrease in utilization of the anticoagulant fondaparinux. In that former trial it reduced mortality and serious bleeding rates in post-myocardial infarction patients, besting enoxaparin; however, the catheter thrombosis rates left the greatest impression, which prompted the addition of UFH for clot prevention and quelled the enthusiasm for this anticoagulant in the percutaneous coronary intervention setting.
This trial sought to resolve the question regarding the optimal dose of heparin when fondaparinux is being used. The double-blind, randomized trial of 2026 patients with non-STE-ACS began by delivering fondaparinux at a dose of 2.5 mg subcutaneously and then if the patients underwent PCI, they were given heparin at a dose of 85 U/kg or if a 2b3a was used they received 60 U/kg. The competing arm of the trial received low-dose UFH at 50 U/kg irrespective of whether they received a 2b3a.
The results were the following: ACS patients treated with fondaparinux can undergo PCI safely with UFH and there were no significant differences in major or minor bleeding or vascular complications between low and standard dose UFH during PCI. Therefore the presenter concluded that there was no need to depart from guideline-recommended standard dose UFH for PCI. Although there was no enoxaparin arm in this trial when compared with OASIS-5, UFH plus fondaparinux does not increase periprocedural major bleeding and with rates apparently lower than those with enoxaparin.
Well that's a wrap for the day in review for the ESC 2010. It's been a pleasure having you join us for practice-changing and thought-provoking trial data. I hope you enjoyed our coverage and please tune in for more updates from the upcoming American Heart Association meeting in November. Thank you and I hope you have a pleasant and most productive day.
I'm Dr. Melissa Walton-Shirley reporting to you on this third day of the European Society of Cardiology (ESC) meeting in Stockholm. It's Tuesday, August 31. Today's hot studies included ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation), which studied the effect of olmesartan on atrial fibrillation recurrence, EINSTEIN DVT (Oral rivaroxaban vs standard therapy in the initial treatment of symptomatic deep vein thrombosis and long-term prevention of recurrent venous thromboembolism) reporting on oral rivaroxaban, and AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes)[3] looking at the factor Xa inhibitor apixaban in stroke prevention. I'll also briefly discuss DANPACE (The Danish multicenter randomized trial on single lead atrial vs dual chamber pacing in sick sinus syndrome), an analysis of single- vs dual-chamber pacing in sick sinus syndrome and then move on to the prevention trial RESPONSE (Effect of a nurse coordinated prevention program on cardiovascular risk after an acute coronary syndrome) and finally FUTURA OASIS-8 (A randomized trial comparing two regimens of adjunctive intravenous unfractionated heparin during PCI in high-risk patients with non-ST-segment elevation acute coronary syndrome treated with fondaparinux) comparing fondaparinux with 2 different unfractionated heparin (UFH) regimens and non-ST-segment elevation acute coronary syndrome (non-STE-ACS).
Let's get started with the ANTIPAF study presented by Dr. Andreas Goette of Germany. This was the first prospective trial that examined the impact of an angiotensin receptor blocker (ARB), specifically olmesartan, on the incidence of atrial fibrillation. Patients who were taking beta-blockers were chosen to participate in the study to remove the question of the impact of that therapy on atrial fibrillation recurrence. The patients were monitored with intermittent home telemetry monitoring with the primary endpoint being that of the percentage of days with documented episodes of atrial fibrillation over 12 months.
Four hundred twenty-five patients submitted 87,181 electrocardiograms for analysis. The unfortunate result was that there was no impact of the ARB olmesartan utilization on atrial fibrillation recurrence rate. This was an important negative trial in the quest to find the right combination for prophylaxis against atrial fibrillation recurrence.
EINSTEIN DVT came to us by way of Dr. Harry Büller of Amsterdam, who presented this trial pitting rivaroxaban, an oral direct factor Xa inhibitor, against standard low-molecular-weight heparin and coumadin or acenocoumarol for treatment of deep venous thrombosis (DVT), but not pulmonary embolism. The treatment arm was a single drug approach from the outset, but was an open-label randomized study powered to evaluate noninferiority to standard care, which it well demonstrated with a P value of less than .0001.
The dosing regimen utilized was 15 mg twice daily for 3 weeks followed by 20 mg once daily for 3, 6, or 12 months depending on the physician's assessment. The primary endpoint of this trial was recurrent DVT with a secondary endpoint of a composite of major and clinically relevant non-major bleeding. The presenter was careful to note that there were no trends of abnormal liver signals noted in this trial.
Rivaroxaban is marketed outside of the United States under the name of Xarelto® and is so far approved for the prophylaxis of DVT. But according to Bloomberg with a second verification from the company they will be seeking regulatory approval for the prevention of embolic stroke in atrial fibrillation by the end of 2010.
Now for the AVERROES study presented by Dr. Stuart Connelly of Ontario. This was a phase 3 trial of yet another factor Xa inhibitor, apixaban, which has already been investigated for the prevention of DVT following orthopaedic surgery. Five thousand six hundred patients with atrial fibrillation were enrolled with a mean age of 70 years and these were patients who were not thought to be optimal candidates for a vitamin K antagonist. The characteristics of those cohorts included simple refusal to take warfarin, increased risk for hemorrhage, or difficult-to-control international normalized ratios (INRs) and included those with intermediate stroke risk as well.
The study drug was compared with aspirin alone. The results were that the primary outcome of stroke or systemic embolization was 3.9% per year with aspirin alone, but only 1.7% on apixaban. The rate of major hemorrhage was 1.4% per year on aspirin and 1.6% on apixaban, but with a nonsignificant P value of 0.33. The rate of hemorrhagic stroke was identical and there was no evidence of hepatotoxicity.
The presenter concluded that it appears that apixaban will be an excellent treatment for many patients with atrial fibrillation who are unsuitable for or are unwilling to take warfarin. These findings will reduce the burden of stroke in society. We were unable to verify when the US Food and Drug Administration approval process will start because the company stated there are no regulatory information pieces to report at this time.
DANPACE was a trial presented by Dr. Jens Nielsen of Denmark and sought to answer the question as to whether single-chamber or dual-chamber pacing was best in the treatment of sick sinus syndrome. Although there are no differences in survival between single-chamber atrial rate-adaptive pacing (AAIR) and dual-chamber rate responsive (DDDR) pacing, the risk for reoperation was double with AAIR pacing and a paroxysmal atrial fibrillation incidence was increased by 27% in single lead pacing.
The final recommendation stemming from this trial was that AAIR pacing should not be used and even more specifically that DDDR pacing with an atrioventricular interval of less than 220 milliseconds is the preferred pacing mode for sick sinus syndrome.
The RESPONSE trial, presented by Dr. Ron Peters of The Netherlands, was an interesting look at secondary prevention where outpatient nursing follow-up was coordinated for patients who had been hospitalized for heart attack or impending heart attack. The trial design included regular nursing follow-up for 754 patients randomized to either usual care alone or usual care plus 6 month nursing interventions that included 4 extra visits to an outpatient clinic for advice on food choices, exercise, smoking, and weight control.
The nurses monitored blood pressure, cholesterol, blood sugar, and preventative medications. Six months after the last nursing visit, which was the 12-month mark following enrollment, the primary endpoint was measured. The nurses were able to achieve a reduction in the risk for death by 17%, but failed in the categories of smoking cessation and weight loss. They did achieve improvements in blood pressure control and low-density lipoprotein cholesterol. It was noted that more than 93% of patients attended all visits, a very impressive display of visit compliance. When asked following the presentation regarding smoking cessation training, there were no cessation medications given and the nurses received no special training in that area.
Finally we have FUTURA OASIS-8, a randomized trial presented by Dr. Jolly of Ontario. The presentation began by referencing OASIS-5, which had previously led to a decrease in utilization of the anticoagulant fondaparinux. In that former trial it reduced mortality and serious bleeding rates in post-myocardial infarction patients, besting enoxaparin; however, the catheter thrombosis rates left the greatest impression, which prompted the addition of UFH for clot prevention and quelled the enthusiasm for this anticoagulant in the percutaneous coronary intervention setting.
This trial sought to resolve the question regarding the optimal dose of heparin when fondaparinux is being used. The double-blind, randomized trial of 2026 patients with non-STE-ACS began by delivering fondaparinux at a dose of 2.5 mg subcutaneously and then if the patients underwent PCI, they were given heparin at a dose of 85 U/kg or if a 2b3a was used they received 60 U/kg. The competing arm of the trial received low-dose UFH at 50 U/kg irrespective of whether they received a 2b3a.
The results were the following: ACS patients treated with fondaparinux can undergo PCI safely with UFH and there were no significant differences in major or minor bleeding or vascular complications between low and standard dose UFH during PCI. Therefore the presenter concluded that there was no need to depart from guideline-recommended standard dose UFH for PCI. Although there was no enoxaparin arm in this trial when compared with OASIS-5, UFH plus fondaparinux does not increase periprocedural major bleeding and with rates apparently lower than those with enoxaparin.
Well that's a wrap for the day in review for the ESC 2010. It's been a pleasure having you join us for practice-changing and thought-provoking trial data. I hope you enjoyed our coverage and please tune in for more updates from the upcoming American Heart Association meeting in November. Thank you and I hope you have a pleasant and most productive day.
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