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Anticoagulation Hub contains news and clinical review articles for physicians seeking the most up-to-date information on the rapidly evolving treatment options for preventing stroke, acute coronary events, deep vein thrombosis, and pulmonary embolism in at-risk patients. The Anticoagulation Hub is powered by Frontline Medical Communications.
VIDEO: NOACs cut intracranial bleeds in real-world atrial fib patients
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.
During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.
These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.
“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.
The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).
In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.
But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.
Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.
He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.
Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
No VTE prophylaxis needed after joint surgery in patients with hemophilia
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
AT WFH 2016 WORLD CONGRESS
Key clinical point: Prophylaxis against thromboembolic events after orthopedic surgery in patients with hemophilia may not be necessary.
Major finding: There were no thromboembolic events after joint surgery without anticoagulant prophylaxis in patients with hemophilia A or B.
Data source: Cohort study of 50 patients with hemophilia A or B undergoing major joint replacement surgery.
Disclosures: The study was internally funded. The investigators reported no conflicts of interest.
Post-AMI death risk model has high predictive accuracy
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: An updated cardiac mortality risk model may help to further reduce in-hospital deaths following acute myocardial infarction.
Major finding: The C-statistic for the model, a measure of predictive accuracy, was 0.88.
Data source: Updated risk model and in-hospital mortality score based on data from 243,440 patients following an AMI in 655 U.S. hospitals.
Disclosures: The ACTION Registry-GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
Study highlights cardiovascular benefits, lower GI risks of low-dose aspirin
Resuming low-dose aspirin after an initial lower gastrointestinal bleed significantly increased the chances of recurrence but protected against serious cardiovascular events, based on a single-center retrospective study published in the August issue of Gastroenterology.
In contrast, “we did not find concomitant use of anticoagulants, antiplatelets, and steroids as a predictor of recurrent lower GI bleeding,” said Dr. Francis Chan of the Prince of Wales Hospital in Hong Kong and his associates. “This may be due to the low percentage of concomitant drug use in both groups. Multicenter studies with a large number of patients will be required to identify additional risk factors for recurrent lower GI bleeding with aspirin use.”
Low-dose aspirin has long been known to help prevent coronary artery and cerebrovascular disease, and more recently has been found to potentially reduce the risk of several types of cancer, the researchers noted. Aspirin is well known to increase the risk of upper GI bleeding, but some studies have also linked it to lower GI bleeding. However, “patients with underlying cardiovascular diseases often require lifelong aspirin,” they added. The risks and benefits of stopping or remaining on aspirin after an initial lower GI bleed are unclear (Gastroenterology 2016 Apr 26. doi: 10.1053/j.gastro.2016.04.013).
Accordingly, the researchers retrospectively studied 295 patients who had an initial aspirin-associated lower GI bleed, defined as 325 mg aspirin a day within a week of bleeding onset. All patients had melena or hematochezia documented by an attending physician and had no endoscopic evidence of upper GI bleeding.
For patients who continued using aspirin at least half the time, the 5-year cumulative incidence of recurrent lower GI bleeding was 19% (95% confidence interval [CI], 13%-25%) – more than double the rate among patients who used aspirin 20% or less of the time (5-year cumulative incidence, 7%; 95% CI, 3%-13%; P = .01). However, the 5-year cumulative incidence of serious cardiovascular events among nonusers was 37% (95% CI, 27%-46%), while the rate among aspirin users was 23% (95% CI, 17%-30%; P = .02). Mortality from noncardiovascular causes was also higher among nonusers (27%) than users (8%; P less than .001), probably because nonusers of aspirin tended to be older than users, but perhaps also because aspirin had a “nonvascular protective effect,” the researchers said.
A multivariate analysis confirmed these findings, linking lower GI bleeding to aspirin but not to use of steroids, anticoagulants, or antiplatelet drugs, or to age, sex, alcohol consumption, smoking, comorbidities, or cardiovascular risks. Indeed, continued aspirin use nearly tripled the chances of a recurrent lower GI bleed (hazard ratio, 2.76; 95% CI, 1.3-6.0; P = .01), but cut the risk of serious cardiovascular events by about 40% (HR, 0.59; 95% CI, 0.4-0.9; P = .02).
Deciding whether to resume aspirin after a severe lower GI bleed “presents a management dilemma for physicians, patients, and their families, particularly in the absence of risk-mitigating therapies and a lack of data on the risks and benefits of resuming aspirin,” the investigators emphasized. Their findings highlight the importance of weighing the cardiovascular benefits of aspirin against GI toxicity, they said. “Since there is substantial risk of recurrent bleeding, physicians should critically evaluate individual patients’ cardiovascular risk before resuming aspirin therapy. Our findings also suggest a need for a composite endpoint to evaluate clinically significant events throughout the GI tract in patients receiving antiplatelet drugs.”
The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.
Resuming low-dose aspirin after an initial lower gastrointestinal bleed significantly increased the chances of recurrence but protected against serious cardiovascular events, based on a single-center retrospective study published in the August issue of Gastroenterology.
In contrast, “we did not find concomitant use of anticoagulants, antiplatelets, and steroids as a predictor of recurrent lower GI bleeding,” said Dr. Francis Chan of the Prince of Wales Hospital in Hong Kong and his associates. “This may be due to the low percentage of concomitant drug use in both groups. Multicenter studies with a large number of patients will be required to identify additional risk factors for recurrent lower GI bleeding with aspirin use.”
Low-dose aspirin has long been known to help prevent coronary artery and cerebrovascular disease, and more recently has been found to potentially reduce the risk of several types of cancer, the researchers noted. Aspirin is well known to increase the risk of upper GI bleeding, but some studies have also linked it to lower GI bleeding. However, “patients with underlying cardiovascular diseases often require lifelong aspirin,” they added. The risks and benefits of stopping or remaining on aspirin after an initial lower GI bleed are unclear (Gastroenterology 2016 Apr 26. doi: 10.1053/j.gastro.2016.04.013).
Accordingly, the researchers retrospectively studied 295 patients who had an initial aspirin-associated lower GI bleed, defined as 325 mg aspirin a day within a week of bleeding onset. All patients had melena or hematochezia documented by an attending physician and had no endoscopic evidence of upper GI bleeding.
For patients who continued using aspirin at least half the time, the 5-year cumulative incidence of recurrent lower GI bleeding was 19% (95% confidence interval [CI], 13%-25%) – more than double the rate among patients who used aspirin 20% or less of the time (5-year cumulative incidence, 7%; 95% CI, 3%-13%; P = .01). However, the 5-year cumulative incidence of serious cardiovascular events among nonusers was 37% (95% CI, 27%-46%), while the rate among aspirin users was 23% (95% CI, 17%-30%; P = .02). Mortality from noncardiovascular causes was also higher among nonusers (27%) than users (8%; P less than .001), probably because nonusers of aspirin tended to be older than users, but perhaps also because aspirin had a “nonvascular protective effect,” the researchers said.
A multivariate analysis confirmed these findings, linking lower GI bleeding to aspirin but not to use of steroids, anticoagulants, or antiplatelet drugs, or to age, sex, alcohol consumption, smoking, comorbidities, or cardiovascular risks. Indeed, continued aspirin use nearly tripled the chances of a recurrent lower GI bleed (hazard ratio, 2.76; 95% CI, 1.3-6.0; P = .01), but cut the risk of serious cardiovascular events by about 40% (HR, 0.59; 95% CI, 0.4-0.9; P = .02).
Deciding whether to resume aspirin after a severe lower GI bleed “presents a management dilemma for physicians, patients, and their families, particularly in the absence of risk-mitigating therapies and a lack of data on the risks and benefits of resuming aspirin,” the investigators emphasized. Their findings highlight the importance of weighing the cardiovascular benefits of aspirin against GI toxicity, they said. “Since there is substantial risk of recurrent bleeding, physicians should critically evaluate individual patients’ cardiovascular risk before resuming aspirin therapy. Our findings also suggest a need for a composite endpoint to evaluate clinically significant events throughout the GI tract in patients receiving antiplatelet drugs.”
The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.
Resuming low-dose aspirin after an initial lower gastrointestinal bleed significantly increased the chances of recurrence but protected against serious cardiovascular events, based on a single-center retrospective study published in the August issue of Gastroenterology.
In contrast, “we did not find concomitant use of anticoagulants, antiplatelets, and steroids as a predictor of recurrent lower GI bleeding,” said Dr. Francis Chan of the Prince of Wales Hospital in Hong Kong and his associates. “This may be due to the low percentage of concomitant drug use in both groups. Multicenter studies with a large number of patients will be required to identify additional risk factors for recurrent lower GI bleeding with aspirin use.”
Low-dose aspirin has long been known to help prevent coronary artery and cerebrovascular disease, and more recently has been found to potentially reduce the risk of several types of cancer, the researchers noted. Aspirin is well known to increase the risk of upper GI bleeding, but some studies have also linked it to lower GI bleeding. However, “patients with underlying cardiovascular diseases often require lifelong aspirin,” they added. The risks and benefits of stopping or remaining on aspirin after an initial lower GI bleed are unclear (Gastroenterology 2016 Apr 26. doi: 10.1053/j.gastro.2016.04.013).
Accordingly, the researchers retrospectively studied 295 patients who had an initial aspirin-associated lower GI bleed, defined as 325 mg aspirin a day within a week of bleeding onset. All patients had melena or hematochezia documented by an attending physician and had no endoscopic evidence of upper GI bleeding.
For patients who continued using aspirin at least half the time, the 5-year cumulative incidence of recurrent lower GI bleeding was 19% (95% confidence interval [CI], 13%-25%) – more than double the rate among patients who used aspirin 20% or less of the time (5-year cumulative incidence, 7%; 95% CI, 3%-13%; P = .01). However, the 5-year cumulative incidence of serious cardiovascular events among nonusers was 37% (95% CI, 27%-46%), while the rate among aspirin users was 23% (95% CI, 17%-30%; P = .02). Mortality from noncardiovascular causes was also higher among nonusers (27%) than users (8%; P less than .001), probably because nonusers of aspirin tended to be older than users, but perhaps also because aspirin had a “nonvascular protective effect,” the researchers said.
A multivariate analysis confirmed these findings, linking lower GI bleeding to aspirin but not to use of steroids, anticoagulants, or antiplatelet drugs, or to age, sex, alcohol consumption, smoking, comorbidities, or cardiovascular risks. Indeed, continued aspirin use nearly tripled the chances of a recurrent lower GI bleed (hazard ratio, 2.76; 95% CI, 1.3-6.0; P = .01), but cut the risk of serious cardiovascular events by about 40% (HR, 0.59; 95% CI, 0.4-0.9; P = .02).
Deciding whether to resume aspirin after a severe lower GI bleed “presents a management dilemma for physicians, patients, and their families, particularly in the absence of risk-mitigating therapies and a lack of data on the risks and benefits of resuming aspirin,” the investigators emphasized. Their findings highlight the importance of weighing the cardiovascular benefits of aspirin against GI toxicity, they said. “Since there is substantial risk of recurrent bleeding, physicians should critically evaluate individual patients’ cardiovascular risk before resuming aspirin therapy. Our findings also suggest a need for a composite endpoint to evaluate clinically significant events throughout the GI tract in patients receiving antiplatelet drugs.”
The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.
FROM GASTROENTEROLOGY
Key clinical point: Resuming low-dose aspirin after a lower gastrointestinal bleed increased the risk of recurrence but protected against cardiovascular events.
Major finding: At 5 years, the cumulative incidence of recurrent lower GI bleeding was 19% for patients who stayed on aspirin and 7% for patients who largely stopped it (P = .01). The cumulative incidence of serious cardiovascular events was 25% for users and 37% for nonusers (P = .02).
Data source: A single-center 5-year retrospective cohort study of 295 patients with aspirin-associated melena or hematochezia and no upper gastrointestinal bleeding.
Disclosures: The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.
AAN recommends against routine closure of patent foramen ovale for secondary stroke prevention
An updated practice advisory from the American Academy of Neurology does not recommend the routine use of catheter-based closure of patent foramen ovale in patients with a history of cryptogenic ischemic stroke.
“Because of the limitations of the efficacy evidence and the potential for serious adverse effects, we judge the risk-benefit trade-offs of PFO [patent foramen ovale] closure by either the STARFlex or AMPLATZER PFO Occluder to be uncertain,” wrote Steven Messé, MD, associate professor of neurology at the University of Pennsylvania, Philadelphia, and his associates. “In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available,” they noted.
They also supported antiplatelet agents over anticoagulants unless patients have another indication for blood thinners, noting “the uncertainty surrounding the benefit of anticoagulation in the setting of PFO, and anticoagulation’s well-known harm profile.”
PFO affects about one in four individuals overall and up to half of cryptogenic stroke patients. The previous (2004) version of this practice advisory cited insufficient evidence to guide optimal therapy for secondary stroke prevention in these patients (Neurology. 2004;Apr 13;62[7]:1042-50). To update the guideline, Dr. Messé and his associates searched the literature for relevant randomized studies, excluding transient ischemic attacks when feasible because of their subjective nature, and focusing on intention-to-treat analyses to reduce bias (Neurology. 2016 Jul 27;doi: 10.1212/WNL.0000000000002961).
Among 809 initial articles, 5 were considered relevant – a randomized, open-label, multicenter study of the STARFlex device (CLOSURE I), two randomized, controlled trials of the AMPLATZER PFO Occluder (PC Trial and RESPECT), and two randomized studies of warfarin versus aspirin in cryptogenic stroke patients, the experts said.
Percutaneous PFO closure with the STARFlex device did not appear to prevent secondary stroke, compared with medical therapy alone, based on a small positive estimated difference in risk of about 0.1%, and a 95% confidence interval that crossed zero (–2.2% to 2.0%). In contrast, the AMPLATZER PFO Occluder decreased the risk of secondary stroke by about 1.7% (95% CI, –3.2% to –0.2%), but upped the risk of procedural complications by more than 3%, and also slightly increased the risk of new-onset atrial fibrillation (1.6%; 95% CI, 0.1% to 3.2%).
Efficacy data were insufficient to clearly support anticoagulants over antiplatelet therapy for recurrent stroke prevention, the experts concluded. Compared with antiplatelet therapy, anticoagulation was associated with a 2% increase in risk of recurrent stroke, but the 95% confidence interval for this estimate was wide and crossed zero. “In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO,” they wrote. “In rare circumstances, such as stroke that recurs while a patient is undergoing antiplatelet therapy, clinicians may offer anticoagulation to patients with cryptogenic stroke and PFO.”
Their strongest recommendation was to counsel patients who are considering percutaneous PFO closure “that having a PFO is common; it occurs in about 1 in 4 people; it is impossible to determine with certainty whether their PFOs caused their strokes or TIAs; the effectiveness of the procedure for reducing stroke risk remains uncertain; and the procedure is associated with relatively uncommon, yet potentially serious, complications.”
The practice advisory was supported by the American Academy of Neurology. Dr. Messé disclosed ties to GlaxoSmithKline and WL Gore & Associates and has been an investigator for the REDUCE and CLOSURE-I trials. Five of his coauthors have been investigators for RESPECT, CLOSURE-I, and REDUCE, have been editors for Neurology, and have received compensation from Genentech, Pfizer, Gilead Sciences, and other pharmaceutical companies. One coauthor had no disclosures.
An updated practice advisory from the American Academy of Neurology does not recommend the routine use of catheter-based closure of patent foramen ovale in patients with a history of cryptogenic ischemic stroke.
“Because of the limitations of the efficacy evidence and the potential for serious adverse effects, we judge the risk-benefit trade-offs of PFO [patent foramen ovale] closure by either the STARFlex or AMPLATZER PFO Occluder to be uncertain,” wrote Steven Messé, MD, associate professor of neurology at the University of Pennsylvania, Philadelphia, and his associates. “In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available,” they noted.
They also supported antiplatelet agents over anticoagulants unless patients have another indication for blood thinners, noting “the uncertainty surrounding the benefit of anticoagulation in the setting of PFO, and anticoagulation’s well-known harm profile.”
PFO affects about one in four individuals overall and up to half of cryptogenic stroke patients. The previous (2004) version of this practice advisory cited insufficient evidence to guide optimal therapy for secondary stroke prevention in these patients (Neurology. 2004;Apr 13;62[7]:1042-50). To update the guideline, Dr. Messé and his associates searched the literature for relevant randomized studies, excluding transient ischemic attacks when feasible because of their subjective nature, and focusing on intention-to-treat analyses to reduce bias (Neurology. 2016 Jul 27;doi: 10.1212/WNL.0000000000002961).
Among 809 initial articles, 5 were considered relevant – a randomized, open-label, multicenter study of the STARFlex device (CLOSURE I), two randomized, controlled trials of the AMPLATZER PFO Occluder (PC Trial and RESPECT), and two randomized studies of warfarin versus aspirin in cryptogenic stroke patients, the experts said.
Percutaneous PFO closure with the STARFlex device did not appear to prevent secondary stroke, compared with medical therapy alone, based on a small positive estimated difference in risk of about 0.1%, and a 95% confidence interval that crossed zero (–2.2% to 2.0%). In contrast, the AMPLATZER PFO Occluder decreased the risk of secondary stroke by about 1.7% (95% CI, –3.2% to –0.2%), but upped the risk of procedural complications by more than 3%, and also slightly increased the risk of new-onset atrial fibrillation (1.6%; 95% CI, 0.1% to 3.2%).
Efficacy data were insufficient to clearly support anticoagulants over antiplatelet therapy for recurrent stroke prevention, the experts concluded. Compared with antiplatelet therapy, anticoagulation was associated with a 2% increase in risk of recurrent stroke, but the 95% confidence interval for this estimate was wide and crossed zero. “In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO,” they wrote. “In rare circumstances, such as stroke that recurs while a patient is undergoing antiplatelet therapy, clinicians may offer anticoagulation to patients with cryptogenic stroke and PFO.”
Their strongest recommendation was to counsel patients who are considering percutaneous PFO closure “that having a PFO is common; it occurs in about 1 in 4 people; it is impossible to determine with certainty whether their PFOs caused their strokes or TIAs; the effectiveness of the procedure for reducing stroke risk remains uncertain; and the procedure is associated with relatively uncommon, yet potentially serious, complications.”
The practice advisory was supported by the American Academy of Neurology. Dr. Messé disclosed ties to GlaxoSmithKline and WL Gore & Associates and has been an investigator for the REDUCE and CLOSURE-I trials. Five of his coauthors have been investigators for RESPECT, CLOSURE-I, and REDUCE, have been editors for Neurology, and have received compensation from Genentech, Pfizer, Gilead Sciences, and other pharmaceutical companies. One coauthor had no disclosures.
An updated practice advisory from the American Academy of Neurology does not recommend the routine use of catheter-based closure of patent foramen ovale in patients with a history of cryptogenic ischemic stroke.
“Because of the limitations of the efficacy evidence and the potential for serious adverse effects, we judge the risk-benefit trade-offs of PFO [patent foramen ovale] closure by either the STARFlex or AMPLATZER PFO Occluder to be uncertain,” wrote Steven Messé, MD, associate professor of neurology at the University of Pennsylvania, Philadelphia, and his associates. “In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available,” they noted.
They also supported antiplatelet agents over anticoagulants unless patients have another indication for blood thinners, noting “the uncertainty surrounding the benefit of anticoagulation in the setting of PFO, and anticoagulation’s well-known harm profile.”
PFO affects about one in four individuals overall and up to half of cryptogenic stroke patients. The previous (2004) version of this practice advisory cited insufficient evidence to guide optimal therapy for secondary stroke prevention in these patients (Neurology. 2004;Apr 13;62[7]:1042-50). To update the guideline, Dr. Messé and his associates searched the literature for relevant randomized studies, excluding transient ischemic attacks when feasible because of their subjective nature, and focusing on intention-to-treat analyses to reduce bias (Neurology. 2016 Jul 27;doi: 10.1212/WNL.0000000000002961).
Among 809 initial articles, 5 were considered relevant – a randomized, open-label, multicenter study of the STARFlex device (CLOSURE I), two randomized, controlled trials of the AMPLATZER PFO Occluder (PC Trial and RESPECT), and two randomized studies of warfarin versus aspirin in cryptogenic stroke patients, the experts said.
Percutaneous PFO closure with the STARFlex device did not appear to prevent secondary stroke, compared with medical therapy alone, based on a small positive estimated difference in risk of about 0.1%, and a 95% confidence interval that crossed zero (–2.2% to 2.0%). In contrast, the AMPLATZER PFO Occluder decreased the risk of secondary stroke by about 1.7% (95% CI, –3.2% to –0.2%), but upped the risk of procedural complications by more than 3%, and also slightly increased the risk of new-onset atrial fibrillation (1.6%; 95% CI, 0.1% to 3.2%).
Efficacy data were insufficient to clearly support anticoagulants over antiplatelet therapy for recurrent stroke prevention, the experts concluded. Compared with antiplatelet therapy, anticoagulation was associated with a 2% increase in risk of recurrent stroke, but the 95% confidence interval for this estimate was wide and crossed zero. “In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO,” they wrote. “In rare circumstances, such as stroke that recurs while a patient is undergoing antiplatelet therapy, clinicians may offer anticoagulation to patients with cryptogenic stroke and PFO.”
Their strongest recommendation was to counsel patients who are considering percutaneous PFO closure “that having a PFO is common; it occurs in about 1 in 4 people; it is impossible to determine with certainty whether their PFOs caused their strokes or TIAs; the effectiveness of the procedure for reducing stroke risk remains uncertain; and the procedure is associated with relatively uncommon, yet potentially serious, complications.”
The practice advisory was supported by the American Academy of Neurology. Dr. Messé disclosed ties to GlaxoSmithKline and WL Gore & Associates and has been an investigator for the REDUCE and CLOSURE-I trials. Five of his coauthors have been investigators for RESPECT, CLOSURE-I, and REDUCE, have been editors for Neurology, and have received compensation from Genentech, Pfizer, Gilead Sciences, and other pharmaceutical companies. One coauthor had no disclosures.
FROM NEUROLOGY
Updated Behçet’s disease recommendations expand biologic treatment
LONDON – A EULAR task force issued the first update to recommendations for managing Behçet’s disease since 2008, with revised recommendations that reflect expanded use of biologic agents, and increased evidence to guide management of gastrointestinal involvement, use of anticoagulants in patients with venous involvement, and use of surgical and interventional treatments, Dr. Gülen Hatemi said while presenting the update at the European Congress of Rheumatology.
The task force, which included more than 20 members, identified 304 articles to apply to the update, and produced five overarching principal and 18 specific recommendations divided among six categories of clinical manifestations of Behçet’s disease, said Dr. Hatemi, convenor of the task force and a rheumatologist at Istanbul University.
For mucocutaneous involvement, the update included five items that all received a “strong” recommendation from the task force: For an oral or genital ulcer, use a topical agent, such as a local steroid. Try colchicine first to prevent recurrent mucocutaneous lesions, especially when the dominant lesion is erythema nodosum or a genital ulcer. Treat papulopustular or acnelike lesions with topical or systemic agents, as when treating acne vulgaris. Coordinate treatment of leg ulcers, which can be caused by venous stasis or obliterative vasculitis, with a dermatologist and vascular surgeon. And azathioprine, thalidomide, interferon-alpha, a tumor necrosis factor (TNF)–alpha antagonist, or apremilast (Otezla) may be necessary for selected patients.
The task force issued two strong recommendations for managing eye involvement along with one conditional recommendation. The first strong recommendation was that managing uveitis requires close collaboration with an ophthalmologist, with the goal of inducing and maintaining remission. Patients with an inflammatory eye disease affecting the posterior segment should receive treatment with azathioprine, cyclosporine, interferon-alpha, or a monoclonal TNF-alpha antagonist. Treatment with a systemic corticosteroid should occur only when combined with azathioprine or another systemic immunosuppressant.
The second strong recommendation was that patients who present with an initial or recurrent acute episode of sight-threatening uveitis should receive treatment with a high-dose glucocorticoid, infliximab, or interferon-alpha. Intravitreal injection with a glucocorticoid as an adjunct to systemic therapy is an option for patients with a unilateral exacerbation. The conditional recommendation was for patients with isolated anterior uveitis. When these patients have markers of a poor prognosis – such as young age, male sex, or early disease onset – systemic treatment with an immunosuppressant is a possible option.
The panel issued three strong recommendations along with one conditional recommendation for managing vascular involvement. One of the strong recommendations called for treating acute deep vein thrombosis with a glucocorticoid as well as an immunosuppresant such as azathioprine, cyclophosphamide, or cyclosporine. A conditional recommendation said patients with refractory venous thrombosis could be considered for treatment with a monoclonal TNF-alpha antagonist, along with an anticoagulant if the patient’s risk for bleeding was generally low and a coexistent pulmonary artery aneurysm was ruled out.
Management of arterial aneurysms received the other two strong recommendations. The panel recommended high-dose glucocorticoid plus cyclophosphamide for a pulmonary artery aneurysm, followed by a monoclonal TNF-alpha antagonist for refractory cases. Patients with these aneurysms who are at high risk for major bleeding should undergo embolization in preference to open surgery. When patients have aortic or peripheral artery aneurysms, treatment should start with cyclophosphamide and a corticosteroid before an aneurysm repair is attempted. But surgery or stenting of the aneurysm should not be delayed when patients are symptomatic.
Gastrointestinal involvement received one strong and two conditional recommendations. The panel strongly recommended confirming gastrointestinal involvement using endoscopy, imaging, or both, while also ruling out treatment with a nonsteroidal anti-inflammatory drug, inflammatory bowel disease, or an infection such as tuberculosis as the cause of gastrointestinal symptoms. One of the conditional recommendations called for an urgent surgical consult when patients have perforation, major bleeding, or obstruction. The second conditional recommendation called for considering glucocorticoid treatment to treat an acute exacerbation of gastrointestinal involvement. Additional treatment options to pair with a glucocorticoid include a disease-modifying drug such as 5-aminosalicylic acid or azathioprine. For patients with severe or refractory gastrointestinal symptoms or both, a monoclonal TNF-alpha antagonist or thalidomide is another potential option.
The panel issued two strong recommendations for managing nervous system involvement. The top treatment option for parenchymal involvement is a high-dose glucocorticoid followed by slow tapering while also treating with an immunosuppressant such as azathioprine. Treatment with cyclosporine should be avoided, the panel said. Treatment with a monoclonal TNF-alpha antagonist is an option to consider as first-line treatment for patients with severe nervous system involvement or for those with refractory disease. The second strong recommendation was to treat a cerebral venous thrombus with a high-dose glucocorticoid followed by tapering, with short-term anticoagulant treatment as an option. Patients also need screening for the presence of vascular disease at an extracranial location.
The panel’s final recommendation was a strong endorsement of colchicine as first-line treatment for arthritis in Behçet’s patients, although patients with acute monoarticular disease can be managed with an intra-articular injection of a glucocorticoid. For patients with recurrent or chronic arthritis, treatment options include azathioprine, interferon-alpha, or a TNF-alpha antagonist.
Dr. Hatemi has received research support from, received honoraria from, or has been a speaker for AbbVie, Celgene, Merck Sharp & Dohme, and Pfizer.
On Twitter @mitchelzoler
LONDON – A EULAR task force issued the first update to recommendations for managing Behçet’s disease since 2008, with revised recommendations that reflect expanded use of biologic agents, and increased evidence to guide management of gastrointestinal involvement, use of anticoagulants in patients with venous involvement, and use of surgical and interventional treatments, Dr. Gülen Hatemi said while presenting the update at the European Congress of Rheumatology.
The task force, which included more than 20 members, identified 304 articles to apply to the update, and produced five overarching principal and 18 specific recommendations divided among six categories of clinical manifestations of Behçet’s disease, said Dr. Hatemi, convenor of the task force and a rheumatologist at Istanbul University.
For mucocutaneous involvement, the update included five items that all received a “strong” recommendation from the task force: For an oral or genital ulcer, use a topical agent, such as a local steroid. Try colchicine first to prevent recurrent mucocutaneous lesions, especially when the dominant lesion is erythema nodosum or a genital ulcer. Treat papulopustular or acnelike lesions with topical or systemic agents, as when treating acne vulgaris. Coordinate treatment of leg ulcers, which can be caused by venous stasis or obliterative vasculitis, with a dermatologist and vascular surgeon. And azathioprine, thalidomide, interferon-alpha, a tumor necrosis factor (TNF)–alpha antagonist, or apremilast (Otezla) may be necessary for selected patients.
The task force issued two strong recommendations for managing eye involvement along with one conditional recommendation. The first strong recommendation was that managing uveitis requires close collaboration with an ophthalmologist, with the goal of inducing and maintaining remission. Patients with an inflammatory eye disease affecting the posterior segment should receive treatment with azathioprine, cyclosporine, interferon-alpha, or a monoclonal TNF-alpha antagonist. Treatment with a systemic corticosteroid should occur only when combined with azathioprine or another systemic immunosuppressant.
The second strong recommendation was that patients who present with an initial or recurrent acute episode of sight-threatening uveitis should receive treatment with a high-dose glucocorticoid, infliximab, or interferon-alpha. Intravitreal injection with a glucocorticoid as an adjunct to systemic therapy is an option for patients with a unilateral exacerbation. The conditional recommendation was for patients with isolated anterior uveitis. When these patients have markers of a poor prognosis – such as young age, male sex, or early disease onset – systemic treatment with an immunosuppressant is a possible option.
The panel issued three strong recommendations along with one conditional recommendation for managing vascular involvement. One of the strong recommendations called for treating acute deep vein thrombosis with a glucocorticoid as well as an immunosuppresant such as azathioprine, cyclophosphamide, or cyclosporine. A conditional recommendation said patients with refractory venous thrombosis could be considered for treatment with a monoclonal TNF-alpha antagonist, along with an anticoagulant if the patient’s risk for bleeding was generally low and a coexistent pulmonary artery aneurysm was ruled out.
Management of arterial aneurysms received the other two strong recommendations. The panel recommended high-dose glucocorticoid plus cyclophosphamide for a pulmonary artery aneurysm, followed by a monoclonal TNF-alpha antagonist for refractory cases. Patients with these aneurysms who are at high risk for major bleeding should undergo embolization in preference to open surgery. When patients have aortic or peripheral artery aneurysms, treatment should start with cyclophosphamide and a corticosteroid before an aneurysm repair is attempted. But surgery or stenting of the aneurysm should not be delayed when patients are symptomatic.
Gastrointestinal involvement received one strong and two conditional recommendations. The panel strongly recommended confirming gastrointestinal involvement using endoscopy, imaging, or both, while also ruling out treatment with a nonsteroidal anti-inflammatory drug, inflammatory bowel disease, or an infection such as tuberculosis as the cause of gastrointestinal symptoms. One of the conditional recommendations called for an urgent surgical consult when patients have perforation, major bleeding, or obstruction. The second conditional recommendation called for considering glucocorticoid treatment to treat an acute exacerbation of gastrointestinal involvement. Additional treatment options to pair with a glucocorticoid include a disease-modifying drug such as 5-aminosalicylic acid or azathioprine. For patients with severe or refractory gastrointestinal symptoms or both, a monoclonal TNF-alpha antagonist or thalidomide is another potential option.
The panel issued two strong recommendations for managing nervous system involvement. The top treatment option for parenchymal involvement is a high-dose glucocorticoid followed by slow tapering while also treating with an immunosuppressant such as azathioprine. Treatment with cyclosporine should be avoided, the panel said. Treatment with a monoclonal TNF-alpha antagonist is an option to consider as first-line treatment for patients with severe nervous system involvement or for those with refractory disease. The second strong recommendation was to treat a cerebral venous thrombus with a high-dose glucocorticoid followed by tapering, with short-term anticoagulant treatment as an option. Patients also need screening for the presence of vascular disease at an extracranial location.
The panel’s final recommendation was a strong endorsement of colchicine as first-line treatment for arthritis in Behçet’s patients, although patients with acute monoarticular disease can be managed with an intra-articular injection of a glucocorticoid. For patients with recurrent or chronic arthritis, treatment options include azathioprine, interferon-alpha, or a TNF-alpha antagonist.
Dr. Hatemi has received research support from, received honoraria from, or has been a speaker for AbbVie, Celgene, Merck Sharp & Dohme, and Pfizer.
On Twitter @mitchelzoler
LONDON – A EULAR task force issued the first update to recommendations for managing Behçet’s disease since 2008, with revised recommendations that reflect expanded use of biologic agents, and increased evidence to guide management of gastrointestinal involvement, use of anticoagulants in patients with venous involvement, and use of surgical and interventional treatments, Dr. Gülen Hatemi said while presenting the update at the European Congress of Rheumatology.
The task force, which included more than 20 members, identified 304 articles to apply to the update, and produced five overarching principal and 18 specific recommendations divided among six categories of clinical manifestations of Behçet’s disease, said Dr. Hatemi, convenor of the task force and a rheumatologist at Istanbul University.
For mucocutaneous involvement, the update included five items that all received a “strong” recommendation from the task force: For an oral or genital ulcer, use a topical agent, such as a local steroid. Try colchicine first to prevent recurrent mucocutaneous lesions, especially when the dominant lesion is erythema nodosum or a genital ulcer. Treat papulopustular or acnelike lesions with topical or systemic agents, as when treating acne vulgaris. Coordinate treatment of leg ulcers, which can be caused by venous stasis or obliterative vasculitis, with a dermatologist and vascular surgeon. And azathioprine, thalidomide, interferon-alpha, a tumor necrosis factor (TNF)–alpha antagonist, or apremilast (Otezla) may be necessary for selected patients.
The task force issued two strong recommendations for managing eye involvement along with one conditional recommendation. The first strong recommendation was that managing uveitis requires close collaboration with an ophthalmologist, with the goal of inducing and maintaining remission. Patients with an inflammatory eye disease affecting the posterior segment should receive treatment with azathioprine, cyclosporine, interferon-alpha, or a monoclonal TNF-alpha antagonist. Treatment with a systemic corticosteroid should occur only when combined with azathioprine or another systemic immunosuppressant.
The second strong recommendation was that patients who present with an initial or recurrent acute episode of sight-threatening uveitis should receive treatment with a high-dose glucocorticoid, infliximab, or interferon-alpha. Intravitreal injection with a glucocorticoid as an adjunct to systemic therapy is an option for patients with a unilateral exacerbation. The conditional recommendation was for patients with isolated anterior uveitis. When these patients have markers of a poor prognosis – such as young age, male sex, or early disease onset – systemic treatment with an immunosuppressant is a possible option.
The panel issued three strong recommendations along with one conditional recommendation for managing vascular involvement. One of the strong recommendations called for treating acute deep vein thrombosis with a glucocorticoid as well as an immunosuppresant such as azathioprine, cyclophosphamide, or cyclosporine. A conditional recommendation said patients with refractory venous thrombosis could be considered for treatment with a monoclonal TNF-alpha antagonist, along with an anticoagulant if the patient’s risk for bleeding was generally low and a coexistent pulmonary artery aneurysm was ruled out.
Management of arterial aneurysms received the other two strong recommendations. The panel recommended high-dose glucocorticoid plus cyclophosphamide for a pulmonary artery aneurysm, followed by a monoclonal TNF-alpha antagonist for refractory cases. Patients with these aneurysms who are at high risk for major bleeding should undergo embolization in preference to open surgery. When patients have aortic or peripheral artery aneurysms, treatment should start with cyclophosphamide and a corticosteroid before an aneurysm repair is attempted. But surgery or stenting of the aneurysm should not be delayed when patients are symptomatic.
Gastrointestinal involvement received one strong and two conditional recommendations. The panel strongly recommended confirming gastrointestinal involvement using endoscopy, imaging, or both, while also ruling out treatment with a nonsteroidal anti-inflammatory drug, inflammatory bowel disease, or an infection such as tuberculosis as the cause of gastrointestinal symptoms. One of the conditional recommendations called for an urgent surgical consult when patients have perforation, major bleeding, or obstruction. The second conditional recommendation called for considering glucocorticoid treatment to treat an acute exacerbation of gastrointestinal involvement. Additional treatment options to pair with a glucocorticoid include a disease-modifying drug such as 5-aminosalicylic acid or azathioprine. For patients with severe or refractory gastrointestinal symptoms or both, a monoclonal TNF-alpha antagonist or thalidomide is another potential option.
The panel issued two strong recommendations for managing nervous system involvement. The top treatment option for parenchymal involvement is a high-dose glucocorticoid followed by slow tapering while also treating with an immunosuppressant such as azathioprine. Treatment with cyclosporine should be avoided, the panel said. Treatment with a monoclonal TNF-alpha antagonist is an option to consider as first-line treatment for patients with severe nervous system involvement or for those with refractory disease. The second strong recommendation was to treat a cerebral venous thrombus with a high-dose glucocorticoid followed by tapering, with short-term anticoagulant treatment as an option. Patients also need screening for the presence of vascular disease at an extracranial location.
The panel’s final recommendation was a strong endorsement of colchicine as first-line treatment for arthritis in Behçet’s patients, although patients with acute monoarticular disease can be managed with an intra-articular injection of a glucocorticoid. For patients with recurrent or chronic arthritis, treatment options include azathioprine, interferon-alpha, or a TNF-alpha antagonist.
Dr. Hatemi has received research support from, received honoraria from, or has been a speaker for AbbVie, Celgene, Merck Sharp & Dohme, and Pfizer.
On Twitter @mitchelzoler
AT THE EULAR 2016 CONGRESS
SLEEP TIGHT: CPAP may be vasculoprotective in stroke/TIA
DENVER – Long-term continuous positive airway pressure (CPAP) for treatment of sleep apnea in patients with a recent mild stroke or transient ischemic attack resulted in improved cardiovascular and metabolic risk factors, better neurologic function, and a reduction in the recurrent vascular event rate, compared with usual care in the SLEEP TIGHT study.
“Up to 25% of patients will have a stroke, cardiovascular event, or death within 90 days after a minor stroke or TIA [transient ischemic attack] despite current preventive strategies. And, importantly, patients with a TIA or stroke have a high prevalence of obstructive sleep apnea – on the order of 60%-80%,” explained Dr. H. Klar Yaggi at the annual meeting of the Associated Professional Sleep Societies.
SLEEP TIGHT’s findings support the hypothesis that diagnosis and treatment of sleep apnea in patients with a recent minor stroke or TIA will address a major unmet need for better methods of reducing the high vascular risk present in this population, said Dr. Yaggi of Yale University in New Haven, Conn.
SLEEP TIGHT was a National Heart, Lung, and Blood Institute–sponsored phase II, 12-month, multicenter, single-blind, randomized, proof-of-concept study. It included 252 patients, 80% of whom had a recent minor stroke, the rest a TIA. These were patients with high levels of cardiovascular risk factors: two-thirds had hypertension, half were hyperlipidemic, 40% had diabetes, 15% had a prior MI, 10% had atrial fibrillation, and the group’s mean body mass index was 30 kg/m2. Polysomnography revealed that 76% of subjects had sleep apnea as defined by an apnea-hypopnea index of at least 5 events per hour. In fact, they averaged about 23 events per hour, putting them in the moderate-severity range. As is common among stroke/TIA patients with sleep apnea, they experienced less daytime sleepiness than is typical in a sleep clinic population, with a mean baseline Epworth Sleepiness Scale score of 7.
Participants were randomized to one of three groups: a usual care control group, a CPAP arm, or an enhanced CPAP arm. The enhanced intervention protocol was designed to boost CPAP adherence; it included targeted education, a customized cognitive intervention, and additional CPAP support beyond the standard CPAP protocols used in sleep medicine clinics. Patients with sleep apnea in the two intervention arms were then placed on CPAP.
At 1 year of follow-up, the stroke rate was 8.7 per 100 patient-years in the usual care group, compared with 5.5 per 100 person-years in the combined intervention arms. The composite cardiovascular event rate, composed of all-cause mortality, acute MI, stroke, hospitalization for unstable angina, or urgent coronary revascularization, was 13.1 per 100 person-years with usual care and 11.0 in the CPAP intervention arms. While these results are encouraging, SLEEP TIGHT wasn’t powered to show significant differences in these hard events.
Outcomes across the board didn’t differ significantly between the CPAP and enhanced CPAP groups. And since the mean number of hours of CPAP use per night was also similar in the two groups – 3.9 hours with standard CPAP and 4.3 hours with enhanced CPAP – it’s likely that the phase III trial will rely upon the much simpler standard CPAP intervention, according to Dr. Yaggi.
He deemed CPAP adherence in this stroke/TIA population to be similar to the rates typically seen in routine sleep medicine practice. Roughly 40% of the stroke/TIA patients were rated as having good adherence, 30% made some use of the therapy, and 30% had no or poor adherence.
Nonetheless, patients in the two intervention arms did significantly better than the usual care group in terms of 1-year changes in insulin resistance and glycosylated hemoglobin. They also had lower 24-hour mean systolic blood pressure and were more likely to convert to a favorable pattern of nocturnal blood pressure dipping. However, no differences between the intervention and usual care groups were seen in levels of high-sensitivity C-reactive protein and interleukin-6, the two markers of systemic inflammation analyzed. Nor did the CPAP intervention provide any benefit in terms of heart rate variability and other measures of autonomic function.
Fifty-eight percent of patients in the intervention arms ended up with a desirable National Institutes of Health Stroke Scale score of 0-1, compared with 38% of the usual care group. In addition, daytime sleepiness as reflected in Epworth Sleepiness Scale scores was reduced at last follow-up to a significantly greater extent in the CPAP groups, Dr. Yaggi noted.
Greater CPAP use was associated with a favorable trend for improvement in the modified Rankin score, a measure of functional ability: a 0.3-point reduction with no or poor CPAP use, a 0.4-point decrease with some use, and a 0.9-point reduction with good use.
The encouraging results will be helpful in designing a planned much larger, event-driven, definitive phase III trial, Dr. Yaggi said.
Dr. Yaggi reported having no financial conflicts regarding this National Heart, Lung and Blood Institute-sponsored study.
DENVER – Long-term continuous positive airway pressure (CPAP) for treatment of sleep apnea in patients with a recent mild stroke or transient ischemic attack resulted in improved cardiovascular and metabolic risk factors, better neurologic function, and a reduction in the recurrent vascular event rate, compared with usual care in the SLEEP TIGHT study.
“Up to 25% of patients will have a stroke, cardiovascular event, or death within 90 days after a minor stroke or TIA [transient ischemic attack] despite current preventive strategies. And, importantly, patients with a TIA or stroke have a high prevalence of obstructive sleep apnea – on the order of 60%-80%,” explained Dr. H. Klar Yaggi at the annual meeting of the Associated Professional Sleep Societies.
SLEEP TIGHT’s findings support the hypothesis that diagnosis and treatment of sleep apnea in patients with a recent minor stroke or TIA will address a major unmet need for better methods of reducing the high vascular risk present in this population, said Dr. Yaggi of Yale University in New Haven, Conn.
SLEEP TIGHT was a National Heart, Lung, and Blood Institute–sponsored phase II, 12-month, multicenter, single-blind, randomized, proof-of-concept study. It included 252 patients, 80% of whom had a recent minor stroke, the rest a TIA. These were patients with high levels of cardiovascular risk factors: two-thirds had hypertension, half were hyperlipidemic, 40% had diabetes, 15% had a prior MI, 10% had atrial fibrillation, and the group’s mean body mass index was 30 kg/m2. Polysomnography revealed that 76% of subjects had sleep apnea as defined by an apnea-hypopnea index of at least 5 events per hour. In fact, they averaged about 23 events per hour, putting them in the moderate-severity range. As is common among stroke/TIA patients with sleep apnea, they experienced less daytime sleepiness than is typical in a sleep clinic population, with a mean baseline Epworth Sleepiness Scale score of 7.
Participants were randomized to one of three groups: a usual care control group, a CPAP arm, or an enhanced CPAP arm. The enhanced intervention protocol was designed to boost CPAP adherence; it included targeted education, a customized cognitive intervention, and additional CPAP support beyond the standard CPAP protocols used in sleep medicine clinics. Patients with sleep apnea in the two intervention arms were then placed on CPAP.
At 1 year of follow-up, the stroke rate was 8.7 per 100 patient-years in the usual care group, compared with 5.5 per 100 person-years in the combined intervention arms. The composite cardiovascular event rate, composed of all-cause mortality, acute MI, stroke, hospitalization for unstable angina, or urgent coronary revascularization, was 13.1 per 100 person-years with usual care and 11.0 in the CPAP intervention arms. While these results are encouraging, SLEEP TIGHT wasn’t powered to show significant differences in these hard events.
Outcomes across the board didn’t differ significantly between the CPAP and enhanced CPAP groups. And since the mean number of hours of CPAP use per night was also similar in the two groups – 3.9 hours with standard CPAP and 4.3 hours with enhanced CPAP – it’s likely that the phase III trial will rely upon the much simpler standard CPAP intervention, according to Dr. Yaggi.
He deemed CPAP adherence in this stroke/TIA population to be similar to the rates typically seen in routine sleep medicine practice. Roughly 40% of the stroke/TIA patients were rated as having good adherence, 30% made some use of the therapy, and 30% had no or poor adherence.
Nonetheless, patients in the two intervention arms did significantly better than the usual care group in terms of 1-year changes in insulin resistance and glycosylated hemoglobin. They also had lower 24-hour mean systolic blood pressure and were more likely to convert to a favorable pattern of nocturnal blood pressure dipping. However, no differences between the intervention and usual care groups were seen in levels of high-sensitivity C-reactive protein and interleukin-6, the two markers of systemic inflammation analyzed. Nor did the CPAP intervention provide any benefit in terms of heart rate variability and other measures of autonomic function.
Fifty-eight percent of patients in the intervention arms ended up with a desirable National Institutes of Health Stroke Scale score of 0-1, compared with 38% of the usual care group. In addition, daytime sleepiness as reflected in Epworth Sleepiness Scale scores was reduced at last follow-up to a significantly greater extent in the CPAP groups, Dr. Yaggi noted.
Greater CPAP use was associated with a favorable trend for improvement in the modified Rankin score, a measure of functional ability: a 0.3-point reduction with no or poor CPAP use, a 0.4-point decrease with some use, and a 0.9-point reduction with good use.
The encouraging results will be helpful in designing a planned much larger, event-driven, definitive phase III trial, Dr. Yaggi said.
Dr. Yaggi reported having no financial conflicts regarding this National Heart, Lung and Blood Institute-sponsored study.
DENVER – Long-term continuous positive airway pressure (CPAP) for treatment of sleep apnea in patients with a recent mild stroke or transient ischemic attack resulted in improved cardiovascular and metabolic risk factors, better neurologic function, and a reduction in the recurrent vascular event rate, compared with usual care in the SLEEP TIGHT study.
“Up to 25% of patients will have a stroke, cardiovascular event, or death within 90 days after a minor stroke or TIA [transient ischemic attack] despite current preventive strategies. And, importantly, patients with a TIA or stroke have a high prevalence of obstructive sleep apnea – on the order of 60%-80%,” explained Dr. H. Klar Yaggi at the annual meeting of the Associated Professional Sleep Societies.
SLEEP TIGHT’s findings support the hypothesis that diagnosis and treatment of sleep apnea in patients with a recent minor stroke or TIA will address a major unmet need for better methods of reducing the high vascular risk present in this population, said Dr. Yaggi of Yale University in New Haven, Conn.
SLEEP TIGHT was a National Heart, Lung, and Blood Institute–sponsored phase II, 12-month, multicenter, single-blind, randomized, proof-of-concept study. It included 252 patients, 80% of whom had a recent minor stroke, the rest a TIA. These were patients with high levels of cardiovascular risk factors: two-thirds had hypertension, half were hyperlipidemic, 40% had diabetes, 15% had a prior MI, 10% had atrial fibrillation, and the group’s mean body mass index was 30 kg/m2. Polysomnography revealed that 76% of subjects had sleep apnea as defined by an apnea-hypopnea index of at least 5 events per hour. In fact, they averaged about 23 events per hour, putting them in the moderate-severity range. As is common among stroke/TIA patients with sleep apnea, they experienced less daytime sleepiness than is typical in a sleep clinic population, with a mean baseline Epworth Sleepiness Scale score of 7.
Participants were randomized to one of three groups: a usual care control group, a CPAP arm, or an enhanced CPAP arm. The enhanced intervention protocol was designed to boost CPAP adherence; it included targeted education, a customized cognitive intervention, and additional CPAP support beyond the standard CPAP protocols used in sleep medicine clinics. Patients with sleep apnea in the two intervention arms were then placed on CPAP.
At 1 year of follow-up, the stroke rate was 8.7 per 100 patient-years in the usual care group, compared with 5.5 per 100 person-years in the combined intervention arms. The composite cardiovascular event rate, composed of all-cause mortality, acute MI, stroke, hospitalization for unstable angina, or urgent coronary revascularization, was 13.1 per 100 person-years with usual care and 11.0 in the CPAP intervention arms. While these results are encouraging, SLEEP TIGHT wasn’t powered to show significant differences in these hard events.
Outcomes across the board didn’t differ significantly between the CPAP and enhanced CPAP groups. And since the mean number of hours of CPAP use per night was also similar in the two groups – 3.9 hours with standard CPAP and 4.3 hours with enhanced CPAP – it’s likely that the phase III trial will rely upon the much simpler standard CPAP intervention, according to Dr. Yaggi.
He deemed CPAP adherence in this stroke/TIA population to be similar to the rates typically seen in routine sleep medicine practice. Roughly 40% of the stroke/TIA patients were rated as having good adherence, 30% made some use of the therapy, and 30% had no or poor adherence.
Nonetheless, patients in the two intervention arms did significantly better than the usual care group in terms of 1-year changes in insulin resistance and glycosylated hemoglobin. They also had lower 24-hour mean systolic blood pressure and were more likely to convert to a favorable pattern of nocturnal blood pressure dipping. However, no differences between the intervention and usual care groups were seen in levels of high-sensitivity C-reactive protein and interleukin-6, the two markers of systemic inflammation analyzed. Nor did the CPAP intervention provide any benefit in terms of heart rate variability and other measures of autonomic function.
Fifty-eight percent of patients in the intervention arms ended up with a desirable National Institutes of Health Stroke Scale score of 0-1, compared with 38% of the usual care group. In addition, daytime sleepiness as reflected in Epworth Sleepiness Scale scores was reduced at last follow-up to a significantly greater extent in the CPAP groups, Dr. Yaggi noted.
Greater CPAP use was associated with a favorable trend for improvement in the modified Rankin score, a measure of functional ability: a 0.3-point reduction with no or poor CPAP use, a 0.4-point decrease with some use, and a 0.9-point reduction with good use.
The encouraging results will be helpful in designing a planned much larger, event-driven, definitive phase III trial, Dr. Yaggi said.
Dr. Yaggi reported having no financial conflicts regarding this National Heart, Lung and Blood Institute-sponsored study.
AT SLEEP 2016
Key clinical point: CPAP treatment of obstructive sleep apnea in patients with a recent TIA or mild stroke appears to reduce their risk of further vascular events.
Major finding: At 1 year of follow-up, the stroke rate in patients randomized to CPAP, including the large subgroup with poor or no adherence, was 5.5 events per 100 person-years, compared with 8.7 in usual care controls.
Data source: SLEEP TIGHT was a 12-month, multicenter, prospective, randomized, single-blind, phase II trial including 252 patients.
Disclosures: The study presenter reported having no financial conflicts regarding this National Heart, Lung, and Blood Institute–sponsored trial.
Prasugrel beats clopidogrel for complex PCI in ACS
PARIS – Patients undergoing complex percutaneous intervention for acute coronary syndrome fared significantly better with prasugrel than clopidogrel as antiplatelet therapy in the large, real-world PROMETHEUS registry, Dr. Jaya Chandrasekhar reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
Cumulative 1-year all-cause mortality was 8% with clopidogrel (Plavix), compared with 2% with prasugrel (Effient), for an adjusted 42% relative risk reduction favoring the more potent oral thienopyridine.
Moreover, the 1-year composite MACE (major adverse cardiac events) outcome comprising death, MI, stroke, or unplanned revascularization occurred in 24.3% of the clopidogrel group, compared with 13.3% of the prasugrel group. That translates to an adjusted 22% relative risk reduction, noted Dr. Chandrasekhar of Mount Sinai Medical Center in New York.
Bleeding rates were similar in the prasugrel and clopidogrel groups, she added.
She stressed that these findings must be viewed as hypothesis-generating rather than definitive, since PROMETHEUS was not a randomized clinical trial. Rather, it was a retrospective observational study of 19,914 patients who underwent PCI for ACS at eight major U.S. medical centers, 20% of whom got prasugrel, 80% clopidogrel. Half of the patients had a complex PCI, defined by Dr. Chandrasekhar and coinvestigators as one targeting the left main coronary artery, any bifurcation lesion, any moderate or severely calcified lesion, or an intervention resulting in a total stent length of 30 mm or longer.
The complex PCI patients were significantly older, by just under 2 years. They had higher rates of diabetes, unstable angina, and multivessel disease, and were more likely to receive at least one second-generation drug-eluting stent.
In a multivariate analysis adjusted for these potential confounders as well as race, body mass index, kidney function, hypertension, hemoglobin, previous PCI, and concomitant use of bivalirudin, the benefits of prasugrel over clopidogrel at 1 year remained significant in patients who underwent complex PCI. In contrast, among the 10,179 ACS patients who underwent noncomplex PCI, the trends favoring lower mortality and MACE in the prasugrel group no longer attained statistical significance upon multivariate adjustment, she said.
Discussant Dr. Pascal Meier said that registry data on prasugrel are inevitably biased because physicians don’t give the drug to patients older than 75 or patients who have had a prior stroke, are low weight, or low risk.
“Do you think there’s any way we can adjust for this bias?” asked Dr. Meier of University Hospital, Geneva.
Dr. Chandrasekhar conceded the possibility of unrecognized confounders.
“I think no matter what statistical methods you use, there will be that potential for bias. This is a real-world study. We understand that physicians and operators select their patients very carefully and the healthier ones get prasugrel rather than clopidogrel.”
She reported having no financial conflicts regarding this study. PROMETHEUS was sponsored and funded by Daiichi Sankyo and Eli Lilly.
PARIS – Patients undergoing complex percutaneous intervention for acute coronary syndrome fared significantly better with prasugrel than clopidogrel as antiplatelet therapy in the large, real-world PROMETHEUS registry, Dr. Jaya Chandrasekhar reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
Cumulative 1-year all-cause mortality was 8% with clopidogrel (Plavix), compared with 2% with prasugrel (Effient), for an adjusted 42% relative risk reduction favoring the more potent oral thienopyridine.
Moreover, the 1-year composite MACE (major adverse cardiac events) outcome comprising death, MI, stroke, or unplanned revascularization occurred in 24.3% of the clopidogrel group, compared with 13.3% of the prasugrel group. That translates to an adjusted 22% relative risk reduction, noted Dr. Chandrasekhar of Mount Sinai Medical Center in New York.
Bleeding rates were similar in the prasugrel and clopidogrel groups, she added.
She stressed that these findings must be viewed as hypothesis-generating rather than definitive, since PROMETHEUS was not a randomized clinical trial. Rather, it was a retrospective observational study of 19,914 patients who underwent PCI for ACS at eight major U.S. medical centers, 20% of whom got prasugrel, 80% clopidogrel. Half of the patients had a complex PCI, defined by Dr. Chandrasekhar and coinvestigators as one targeting the left main coronary artery, any bifurcation lesion, any moderate or severely calcified lesion, or an intervention resulting in a total stent length of 30 mm or longer.
The complex PCI patients were significantly older, by just under 2 years. They had higher rates of diabetes, unstable angina, and multivessel disease, and were more likely to receive at least one second-generation drug-eluting stent.
In a multivariate analysis adjusted for these potential confounders as well as race, body mass index, kidney function, hypertension, hemoglobin, previous PCI, and concomitant use of bivalirudin, the benefits of prasugrel over clopidogrel at 1 year remained significant in patients who underwent complex PCI. In contrast, among the 10,179 ACS patients who underwent noncomplex PCI, the trends favoring lower mortality and MACE in the prasugrel group no longer attained statistical significance upon multivariate adjustment, she said.
Discussant Dr. Pascal Meier said that registry data on prasugrel are inevitably biased because physicians don’t give the drug to patients older than 75 or patients who have had a prior stroke, are low weight, or low risk.
“Do you think there’s any way we can adjust for this bias?” asked Dr. Meier of University Hospital, Geneva.
Dr. Chandrasekhar conceded the possibility of unrecognized confounders.
“I think no matter what statistical methods you use, there will be that potential for bias. This is a real-world study. We understand that physicians and operators select their patients very carefully and the healthier ones get prasugrel rather than clopidogrel.”
She reported having no financial conflicts regarding this study. PROMETHEUS was sponsored and funded by Daiichi Sankyo and Eli Lilly.
PARIS – Patients undergoing complex percutaneous intervention for acute coronary syndrome fared significantly better with prasugrel than clopidogrel as antiplatelet therapy in the large, real-world PROMETHEUS registry, Dr. Jaya Chandrasekhar reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
Cumulative 1-year all-cause mortality was 8% with clopidogrel (Plavix), compared with 2% with prasugrel (Effient), for an adjusted 42% relative risk reduction favoring the more potent oral thienopyridine.
Moreover, the 1-year composite MACE (major adverse cardiac events) outcome comprising death, MI, stroke, or unplanned revascularization occurred in 24.3% of the clopidogrel group, compared with 13.3% of the prasugrel group. That translates to an adjusted 22% relative risk reduction, noted Dr. Chandrasekhar of Mount Sinai Medical Center in New York.
Bleeding rates were similar in the prasugrel and clopidogrel groups, she added.
She stressed that these findings must be viewed as hypothesis-generating rather than definitive, since PROMETHEUS was not a randomized clinical trial. Rather, it was a retrospective observational study of 19,914 patients who underwent PCI for ACS at eight major U.S. medical centers, 20% of whom got prasugrel, 80% clopidogrel. Half of the patients had a complex PCI, defined by Dr. Chandrasekhar and coinvestigators as one targeting the left main coronary artery, any bifurcation lesion, any moderate or severely calcified lesion, or an intervention resulting in a total stent length of 30 mm or longer.
The complex PCI patients were significantly older, by just under 2 years. They had higher rates of diabetes, unstable angina, and multivessel disease, and were more likely to receive at least one second-generation drug-eluting stent.
In a multivariate analysis adjusted for these potential confounders as well as race, body mass index, kidney function, hypertension, hemoglobin, previous PCI, and concomitant use of bivalirudin, the benefits of prasugrel over clopidogrel at 1 year remained significant in patients who underwent complex PCI. In contrast, among the 10,179 ACS patients who underwent noncomplex PCI, the trends favoring lower mortality and MACE in the prasugrel group no longer attained statistical significance upon multivariate adjustment, she said.
Discussant Dr. Pascal Meier said that registry data on prasugrel are inevitably biased because physicians don’t give the drug to patients older than 75 or patients who have had a prior stroke, are low weight, or low risk.
“Do you think there’s any way we can adjust for this bias?” asked Dr. Meier of University Hospital, Geneva.
Dr. Chandrasekhar conceded the possibility of unrecognized confounders.
“I think no matter what statistical methods you use, there will be that potential for bias. This is a real-world study. We understand that physicians and operators select their patients very carefully and the healthier ones get prasugrel rather than clopidogrel.”
She reported having no financial conflicts regarding this study. PROMETHEUS was sponsored and funded by Daiichi Sankyo and Eli Lilly.
AT EUROPCR 2016
Key clinical point: One-year outcomes were significantly better following complex PCI for acute coronary syndrome in prasugrel rather than in clopidogrel recipients.
Major finding: The composite rate of mortality, MI, stroke, or unplanned revascularization 1 year after patients underwent complex PCI for ACS was 13.3% in those who received prasugrel, compared with 24.3% in patients given clopidogrel.
Data source: PROMETHEUS, a retrospective observational study of 19,914 patients who underwent PCI for ACS at eight major U.S. medical centers.
Disclosures: Daiichi Sankyo and Eli Lilly sponsored and funded the study. The presenter reported having no conflicts of interest.
Rotor ablation for atrial fibrillation strikes out in first randomized trial
SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.
In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.
“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.
“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.
In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.
At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).
Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).
There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”
Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.
All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.
There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.
My gut sense is that there’s something to rotor mapping, but we are not there yet. There are a lot of investment dollars and a lot of bright people working on this. It really is the Holy Grail to find the source of AF.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He had no disclosures.
My gut sense is that there’s something to rotor mapping, but we are not there yet. There are a lot of investment dollars and a lot of bright people working on this. It really is the Holy Grail to find the source of AF.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He had no disclosures.
My gut sense is that there’s something to rotor mapping, but we are not there yet. There are a lot of investment dollars and a lot of bright people working on this. It really is the Holy Grail to find the source of AF.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He had no disclosures.
SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.
In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.
“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.
“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.
In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.
At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).
Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).
There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”
Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.
All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.
There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.
SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.
In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.
“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.
“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.
In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.
At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).
Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).
There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”
Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.
All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.
There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.
AT HEART RHYTHM 2016
Key clinical point: Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes.
Major finding: At about 1 year, four rotor ablation-only patients (14%), 22 RA plus pulmonary vein antral isolation patients (52.4%), and 32 patients in the PVAI plus trigger group (76%) were free of atrial fibrillation and atrial tachycardias without antiarrhythmic drugs (P < .0001).
Data source: A randomized trial in 113 persistent AF patients.
Disclosures: There was no industry funding for the work. The senior investigator disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.
PVI redo at 2 months drops 1 year AF recurrence by 30%
SAN FRANCISCO – Repeat, invasive electrophysiology studies conducted 2 months after pulmonary vein isolation – regardless of symptoms and, if necessary, with repeat ablations – substantially reduce atrial fibrillation recurrence and improve quality of life at 1 year, according to an investigation conducted at the Liverpool (Eng.) Heart and Chest Hospital.
After initial pulmonary vein isolation (PVI), 40 patients with drug-refractory, paroxysmal atrial fibrillation (AF) were randomized to the repeat approach, and 40 others to the current standard of care (SC), meaning repeat PVI based on recurrent AF symptoms.
Pulmonary vein reconnections were found in 25 patients (63%) checked at 2 months, and all 25 had repeat PVIs without complications. Meanwhile, nine (23%) patients in the SC group had repeat PVIs for clinical recurrence at a mean of about 7 months.
At one year, 33 patients in the repeat group (82.5%), but only 23 in the SC group (57.5%), were free of atrial tachyarrhythmia (AT) (P = .03), and total group AT burden was lower (91 versus 127 days, P = .03). Quality of life scores on the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire were higher in the repeat study group, too (mean 92.2 versus 79.1 out of 126 points, P = .030).
“A strategy of early assessment with re-isolation of PV reconnections can be deployed safely and improves freedom from AT recurrence and quality of life compared with current standard care. While the gold standard remains durable PVI from the initial procedure, until rates of this can be substantially improved, early re-intervention could be considered as a reasonable strategy to improve outcomes,” the investigators concluded.
“If it was my dad and I was doing a PVI today, I’d say, ‘Dad, let’s bring you back and look at how you’re doing in 2 months,’” lead investigator Dr. Dhiraj Gupta said during an interview after his presentation at the Heart Rhythm Society annual meeting.
“We can’t really afford to do everybody twice, but this has certainly lowered our threshold for reintervention,” said Dr. Gupta, a cardiologist at the Liverpool hospital. “We used to try antiarrhythmic drugs” for recurrence; “we don’t do that anymore. We complete the job that [we] set out to do in the first place. Our threshold is any recurrence beyond 1 month. A surprising number of patients agree with this [recheck] strategy, which is one of the reasons we didn’t have a single drop out in this study. I tell them that it’s highly likely that some of the pulmonary veins I isolated for them are going to reconnect.”
Audience members were concerned that 15 patients in the study arm (38%) ended up having an invasive test they didn’t need. Dr. Gupta said it’s a “glass half full or half empty” situation. “I see it as half full. These repeat procedures are short, safe, and quick [about 80 minutes], and even shorter for those patients who don’t require pulmonary reisolation.” For those patients who do, only a few have symptoms; the rest would have had to wait for remergent symptoms to trigger a second procedure. “I believe that these repeat procedures have become so safe that the risk is more than made up” for by the benefits.
There were no complications with early reinterventions, and there were just two complications with the original PVI; one patient who ended up in the repeat group had a spontaneously resolving phrenic nerve palsy with the first procedure, and one SC patient had a transient ischemic attack. In short, “the complication rates for the two groups were identical,” Dr. Gupta said.
Patients were split about evenly between men and women in both study arms, and patients were in their early 60s, on average. The mean baseline AFEQT score was 46.8 points; 78% in the standard care group, but 55% in the early reintervention group, were on baseline anticoagulants.
All of the subjects were given portable ECG recorders after their initial PVIs, and told to take a daily 30-second recording, and to record if they felt any heart symptoms. They followed the instructions and made more than 32,000 recordings.
Every PVI patient at the Liverpool hospital now gets a recorder at discharge, and physicians there base early interventions on the results, whether or not patients are symptomatic. “We’ve bought lots of them, and tell patients to have a low threshold for recording. I believe 24-hours Holters are a bit outdated,” Dr. Gupta said.
All the PVIs in the study were contact-force guided and used wide area circumferential ablation with the help of 3-D mapping and automated lesion tagging. Entrance and exit block were demonstrated, and adenosine was administered to unmask dormant reconnections after a waiting period of at least 20 minutes. Antiarrhythmic drugs were stopped at 4 weeks.
Biosense Webster funded the work. Dr. Gupta is a speaker for and receives research and fellowship funding from the company.
This is a provocative study, but the redo rate was very low in the standard of care arm [23%], much lower than we typically see. In my mind, they should have been more aggressive with that group. I would love to see them repeat this study but with a redo procedure in the standard of care arm with the first recurrence after 2 months.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He has no disclosures.
This is a provocative study, but the redo rate was very low in the standard of care arm [23%], much lower than we typically see. In my mind, they should have been more aggressive with that group. I would love to see them repeat this study but with a redo procedure in the standard of care arm with the first recurrence after 2 months.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He has no disclosures.
This is a provocative study, but the redo rate was very low in the standard of care arm [23%], much lower than we typically see. In my mind, they should have been more aggressive with that group. I would love to see them repeat this study but with a redo procedure in the standard of care arm with the first recurrence after 2 months.
Dr. John Day is the director of Intermountain Heart Rhythm Specialists in Murray, Utah, and the current president of the Hearth Rhythm Society. He has no disclosures.
SAN FRANCISCO – Repeat, invasive electrophysiology studies conducted 2 months after pulmonary vein isolation – regardless of symptoms and, if necessary, with repeat ablations – substantially reduce atrial fibrillation recurrence and improve quality of life at 1 year, according to an investigation conducted at the Liverpool (Eng.) Heart and Chest Hospital.
After initial pulmonary vein isolation (PVI), 40 patients with drug-refractory, paroxysmal atrial fibrillation (AF) were randomized to the repeat approach, and 40 others to the current standard of care (SC), meaning repeat PVI based on recurrent AF symptoms.
Pulmonary vein reconnections were found in 25 patients (63%) checked at 2 months, and all 25 had repeat PVIs without complications. Meanwhile, nine (23%) patients in the SC group had repeat PVIs for clinical recurrence at a mean of about 7 months.
At one year, 33 patients in the repeat group (82.5%), but only 23 in the SC group (57.5%), were free of atrial tachyarrhythmia (AT) (P = .03), and total group AT burden was lower (91 versus 127 days, P = .03). Quality of life scores on the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire were higher in the repeat study group, too (mean 92.2 versus 79.1 out of 126 points, P = .030).
“A strategy of early assessment with re-isolation of PV reconnections can be deployed safely and improves freedom from AT recurrence and quality of life compared with current standard care. While the gold standard remains durable PVI from the initial procedure, until rates of this can be substantially improved, early re-intervention could be considered as a reasonable strategy to improve outcomes,” the investigators concluded.
“If it was my dad and I was doing a PVI today, I’d say, ‘Dad, let’s bring you back and look at how you’re doing in 2 months,’” lead investigator Dr. Dhiraj Gupta said during an interview after his presentation at the Heart Rhythm Society annual meeting.
“We can’t really afford to do everybody twice, but this has certainly lowered our threshold for reintervention,” said Dr. Gupta, a cardiologist at the Liverpool hospital. “We used to try antiarrhythmic drugs” for recurrence; “we don’t do that anymore. We complete the job that [we] set out to do in the first place. Our threshold is any recurrence beyond 1 month. A surprising number of patients agree with this [recheck] strategy, which is one of the reasons we didn’t have a single drop out in this study. I tell them that it’s highly likely that some of the pulmonary veins I isolated for them are going to reconnect.”
Audience members were concerned that 15 patients in the study arm (38%) ended up having an invasive test they didn’t need. Dr. Gupta said it’s a “glass half full or half empty” situation. “I see it as half full. These repeat procedures are short, safe, and quick [about 80 minutes], and even shorter for those patients who don’t require pulmonary reisolation.” For those patients who do, only a few have symptoms; the rest would have had to wait for remergent symptoms to trigger a second procedure. “I believe that these repeat procedures have become so safe that the risk is more than made up” for by the benefits.
There were no complications with early reinterventions, and there were just two complications with the original PVI; one patient who ended up in the repeat group had a spontaneously resolving phrenic nerve palsy with the first procedure, and one SC patient had a transient ischemic attack. In short, “the complication rates for the two groups were identical,” Dr. Gupta said.
Patients were split about evenly between men and women in both study arms, and patients were in their early 60s, on average. The mean baseline AFEQT score was 46.8 points; 78% in the standard care group, but 55% in the early reintervention group, were on baseline anticoagulants.
All of the subjects were given portable ECG recorders after their initial PVIs, and told to take a daily 30-second recording, and to record if they felt any heart symptoms. They followed the instructions and made more than 32,000 recordings.
Every PVI patient at the Liverpool hospital now gets a recorder at discharge, and physicians there base early interventions on the results, whether or not patients are symptomatic. “We’ve bought lots of them, and tell patients to have a low threshold for recording. I believe 24-hours Holters are a bit outdated,” Dr. Gupta said.
All the PVIs in the study were contact-force guided and used wide area circumferential ablation with the help of 3-D mapping and automated lesion tagging. Entrance and exit block were demonstrated, and adenosine was administered to unmask dormant reconnections after a waiting period of at least 20 minutes. Antiarrhythmic drugs were stopped at 4 weeks.
Biosense Webster funded the work. Dr. Gupta is a speaker for and receives research and fellowship funding from the company.
SAN FRANCISCO – Repeat, invasive electrophysiology studies conducted 2 months after pulmonary vein isolation – regardless of symptoms and, if necessary, with repeat ablations – substantially reduce atrial fibrillation recurrence and improve quality of life at 1 year, according to an investigation conducted at the Liverpool (Eng.) Heart and Chest Hospital.
After initial pulmonary vein isolation (PVI), 40 patients with drug-refractory, paroxysmal atrial fibrillation (AF) were randomized to the repeat approach, and 40 others to the current standard of care (SC), meaning repeat PVI based on recurrent AF symptoms.
Pulmonary vein reconnections were found in 25 patients (63%) checked at 2 months, and all 25 had repeat PVIs without complications. Meanwhile, nine (23%) patients in the SC group had repeat PVIs for clinical recurrence at a mean of about 7 months.
At one year, 33 patients in the repeat group (82.5%), but only 23 in the SC group (57.5%), were free of atrial tachyarrhythmia (AT) (P = .03), and total group AT burden was lower (91 versus 127 days, P = .03). Quality of life scores on the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire were higher in the repeat study group, too (mean 92.2 versus 79.1 out of 126 points, P = .030).
“A strategy of early assessment with re-isolation of PV reconnections can be deployed safely and improves freedom from AT recurrence and quality of life compared with current standard care. While the gold standard remains durable PVI from the initial procedure, until rates of this can be substantially improved, early re-intervention could be considered as a reasonable strategy to improve outcomes,” the investigators concluded.
“If it was my dad and I was doing a PVI today, I’d say, ‘Dad, let’s bring you back and look at how you’re doing in 2 months,’” lead investigator Dr. Dhiraj Gupta said during an interview after his presentation at the Heart Rhythm Society annual meeting.
“We can’t really afford to do everybody twice, but this has certainly lowered our threshold for reintervention,” said Dr. Gupta, a cardiologist at the Liverpool hospital. “We used to try antiarrhythmic drugs” for recurrence; “we don’t do that anymore. We complete the job that [we] set out to do in the first place. Our threshold is any recurrence beyond 1 month. A surprising number of patients agree with this [recheck] strategy, which is one of the reasons we didn’t have a single drop out in this study. I tell them that it’s highly likely that some of the pulmonary veins I isolated for them are going to reconnect.”
Audience members were concerned that 15 patients in the study arm (38%) ended up having an invasive test they didn’t need. Dr. Gupta said it’s a “glass half full or half empty” situation. “I see it as half full. These repeat procedures are short, safe, and quick [about 80 minutes], and even shorter for those patients who don’t require pulmonary reisolation.” For those patients who do, only a few have symptoms; the rest would have had to wait for remergent symptoms to trigger a second procedure. “I believe that these repeat procedures have become so safe that the risk is more than made up” for by the benefits.
There were no complications with early reinterventions, and there were just two complications with the original PVI; one patient who ended up in the repeat group had a spontaneously resolving phrenic nerve palsy with the first procedure, and one SC patient had a transient ischemic attack. In short, “the complication rates for the two groups were identical,” Dr. Gupta said.
Patients were split about evenly between men and women in both study arms, and patients were in their early 60s, on average. The mean baseline AFEQT score was 46.8 points; 78% in the standard care group, but 55% in the early reintervention group, were on baseline anticoagulants.
All of the subjects were given portable ECG recorders after their initial PVIs, and told to take a daily 30-second recording, and to record if they felt any heart symptoms. They followed the instructions and made more than 32,000 recordings.
Every PVI patient at the Liverpool hospital now gets a recorder at discharge, and physicians there base early interventions on the results, whether or not patients are symptomatic. “We’ve bought lots of them, and tell patients to have a low threshold for recording. I believe 24-hours Holters are a bit outdated,” Dr. Gupta said.
All the PVIs in the study were contact-force guided and used wide area circumferential ablation with the help of 3-D mapping and automated lesion tagging. Entrance and exit block were demonstrated, and adenosine was administered to unmask dormant reconnections after a waiting period of at least 20 minutes. Antiarrhythmic drugs were stopped at 4 weeks.
Biosense Webster funded the work. Dr. Gupta is a speaker for and receives research and fellowship funding from the company.
AT HEART RHYTHM 2016
Key clinical point: Repeat, invasive electrophysiology studies 2 months after pulmonary vein isolation – regardless of symptoms and, if necessary, with repeat ablations – substantially reduce atrial fibrillation recurrence and improve quality of life at 1 year.
Major finding: Thirty-three patients in the repeat group (82.5%), but only 23 in the SC group (57.5%), were free of atrial tachyarrhythmias at 12 months (P = .03).
Data source: Randomized study in 80 drug-refractory, paroxysmal atrial fibrillation patients
Disclosures: Biosense Webster funded the work. Dr. Gupta is a speaker for and receives research and fellowship funding from Biosense Webster.