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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
CT opens extended window for stroke thrombolysis
MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.
“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”
The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).
“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.
“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.
CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.
The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.
The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.
The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.
Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”
These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.
“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.
Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.
SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.
Ever since results from the WAKE-UP trial came out earlier in 2018, we at the University of Cincinnati have been imaging acute ischemic stroke patients who presented outside the standard 4.5-hour time limit for thrombolysis with MRI to see if they qualify for an extended window for thrombolysis. But this has been a cumbersome and redundant process because our default imaging method is CT, so we have been imaging potential candidates for an extended thrombolytic window twice, first with CT and then later with MRI.
The EXTEND findings also provide a further reason for U.S. stroke centers to purchase and use some type of imaging processing software if they don’t already have it, either the RAPID software that was used in EXTEND or one of the several similar software packages that are now available. Several primary stroke centers in my area still do not currently use this software, although its use has been quickly spreading and it will now be increasingly hard for these centers to hold off acquiring it. Fortunately the increased competition among software vendors who sell this type of software has meant that the price has been dropping.
Pooja Khatri, MD , is a professor of neurology and director of acute stroke at the University of Cincinnati. She has been a consultant to Biogen, Greenwich, and PTC Therapeutics. She made these comments in an interview.
Ever since results from the WAKE-UP trial came out earlier in 2018, we at the University of Cincinnati have been imaging acute ischemic stroke patients who presented outside the standard 4.5-hour time limit for thrombolysis with MRI to see if they qualify for an extended window for thrombolysis. But this has been a cumbersome and redundant process because our default imaging method is CT, so we have been imaging potential candidates for an extended thrombolytic window twice, first with CT and then later with MRI.
The EXTEND findings also provide a further reason for U.S. stroke centers to purchase and use some type of imaging processing software if they don’t already have it, either the RAPID software that was used in EXTEND or one of the several similar software packages that are now available. Several primary stroke centers in my area still do not currently use this software, although its use has been quickly spreading and it will now be increasingly hard for these centers to hold off acquiring it. Fortunately the increased competition among software vendors who sell this type of software has meant that the price has been dropping.
Pooja Khatri, MD , is a professor of neurology and director of acute stroke at the University of Cincinnati. She has been a consultant to Biogen, Greenwich, and PTC Therapeutics. She made these comments in an interview.
Ever since results from the WAKE-UP trial came out earlier in 2018, we at the University of Cincinnati have been imaging acute ischemic stroke patients who presented outside the standard 4.5-hour time limit for thrombolysis with MRI to see if they qualify for an extended window for thrombolysis. But this has been a cumbersome and redundant process because our default imaging method is CT, so we have been imaging potential candidates for an extended thrombolytic window twice, first with CT and then later with MRI.
The EXTEND findings also provide a further reason for U.S. stroke centers to purchase and use some type of imaging processing software if they don’t already have it, either the RAPID software that was used in EXTEND or one of the several similar software packages that are now available. Several primary stroke centers in my area still do not currently use this software, although its use has been quickly spreading and it will now be increasingly hard for these centers to hold off acquiring it. Fortunately the increased competition among software vendors who sell this type of software has meant that the price has been dropping.
Pooja Khatri, MD , is a professor of neurology and director of acute stroke at the University of Cincinnati. She has been a consultant to Biogen, Greenwich, and PTC Therapeutics. She made these comments in an interview.
MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.
“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”
The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).
“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.
“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.
CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.
The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.
The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.
The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.
Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”
These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.
“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.
Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.
SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.
MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.
“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”
The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).
“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.
“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.
CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.
The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.
The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.
The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.
Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”
These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.
“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.
Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.
SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.
REPORTING FROM THE WORLD STROKE CONGRESS
Key clinical point:
Major finding: Patients who received thrombolysis 4.5-9 hours after stroke onset had a 44% increased rate of good outcomes, compared with controls.
Study details: EXTEND, a multicenter, controlled trial with 225 patients.
Disclosures: Dr. Ma and Dr. Shuaib had no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.
Source: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.
TENS cuts fibromyalgia pain in large RCT
CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.
The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.
The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.
TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.
“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.
“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.
“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.
“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”
TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m2.
The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.
FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.
SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.
This was an encouraging result for a potential benefit from transcutaneous electrical nerve stimulation (TENS). For patients with fibromyalgia who are not having a good outcome with standard treatments I would certainly offer TENS. It’s always good to be able to show patients study results that document a treatment’s benefit. Patients like to get pain relief, even if it is short lived. Wearing a device for 2 hours a day is not a problem for many patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University, Durham, N.C. He has financial relationships with Amgen, Celgene, Celltrion, and ImmunArray. He made these comments in an interview.
This was an encouraging result for a potential benefit from transcutaneous electrical nerve stimulation (TENS). For patients with fibromyalgia who are not having a good outcome with standard treatments I would certainly offer TENS. It’s always good to be able to show patients study results that document a treatment’s benefit. Patients like to get pain relief, even if it is short lived. Wearing a device for 2 hours a day is not a problem for many patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University, Durham, N.C. He has financial relationships with Amgen, Celgene, Celltrion, and ImmunArray. He made these comments in an interview.
This was an encouraging result for a potential benefit from transcutaneous electrical nerve stimulation (TENS). For patients with fibromyalgia who are not having a good outcome with standard treatments I would certainly offer TENS. It’s always good to be able to show patients study results that document a treatment’s benefit. Patients like to get pain relief, even if it is short lived. Wearing a device for 2 hours a day is not a problem for many patients.
David S. Pisetsky, MD , is a professor of medicine at Duke University, Durham, N.C. He has financial relationships with Amgen, Celgene, Celltrion, and ImmunArray. He made these comments in an interview.
CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.
The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.
The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.
TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.
“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.
“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.
“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.
“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”
TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m2.
The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.
FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.
SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.
CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.
The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.
The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.
TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.
“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.
“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.
“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.
“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”
TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m2.
The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.
FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.
SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Transcutaneous electrical nerve stimulation showed efficacy and safety in a large randomized, controlled trial.
Major finding: Active transcutaneous electrical nerve stimulation produced at least a 30% pain reduction in 44% of patients, while 22% had this response to mock transcutaneous electrical nerve stimulation.
Study details: FAST, a randomized, controlled trial with 301 patients at two U.S. centers.
Disclosures: FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.
Source: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.
Risk score validated for major NSAID adverse events
CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.
The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.
Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m2, and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.
The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.
The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.
As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.
Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.
PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.
SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).
CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.
The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.
Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m2, and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.
The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.
The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.
As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.
Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.
PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.
SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).
CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.
The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.
Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m2, and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.
The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.
The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.
As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.
Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.
PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.
SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Five percent of patients had a predicted risk below 1%; 70% had 1%-4% risk; 25% had greater than 4% risk.
Study details: Derivation and validation of the risk score used data from 23,950 patients in the PRECISION trial.
Disclosures: PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.
Source: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).
SLE low-disease definition receives prospective validation
CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.
The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.
The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):
• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.
• No new disease activity.
• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.
• Maintenance on a prednisolone dosage of 7.5 mg/day or less.
• Maintenance on a standard immunosuppressive regimen.
The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).
The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.
The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.
Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.
The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.
SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.
Having a validated, formal definition of low disease activity in patients with systemic lupus erythematosus will be very helpful to clinicians and patients with this disease. The lack of such a widely accepted definition of a treatment target until now has been a significant issue that had made it more challenging to advise and treat patients.
The concept of a low disease state has been much easier to define in other rheumatic diseases, but lupus has posed a major challenge because of its very heterogeneous presentation. This heterogeneity has led to the creation of several measures of disease activity as well as multiple serologic parameters that also help define disease activity. It’s unrealistic to expect most lupus patients to be in a low disease activity state all the time.
Validation of a reasonable definition of low activity is a great, pragmatic step forward for our field that will help clinicians better care for their patients with systemic lupus erythematosus.
Lisa R. Sammaritano, MD , is a rheumatologist at the Hospital for Special Surgery and Cornell University in New York. She had no disclosures. She made these comments in an interview.
Having a validated, formal definition of low disease activity in patients with systemic lupus erythematosus will be very helpful to clinicians and patients with this disease. The lack of such a widely accepted definition of a treatment target until now has been a significant issue that had made it more challenging to advise and treat patients.
The concept of a low disease state has been much easier to define in other rheumatic diseases, but lupus has posed a major challenge because of its very heterogeneous presentation. This heterogeneity has led to the creation of several measures of disease activity as well as multiple serologic parameters that also help define disease activity. It’s unrealistic to expect most lupus patients to be in a low disease activity state all the time.
Validation of a reasonable definition of low activity is a great, pragmatic step forward for our field that will help clinicians better care for their patients with systemic lupus erythematosus.
Lisa R. Sammaritano, MD , is a rheumatologist at the Hospital for Special Surgery and Cornell University in New York. She had no disclosures. She made these comments in an interview.
Having a validated, formal definition of low disease activity in patients with systemic lupus erythematosus will be very helpful to clinicians and patients with this disease. The lack of such a widely accepted definition of a treatment target until now has been a significant issue that had made it more challenging to advise and treat patients.
The concept of a low disease state has been much easier to define in other rheumatic diseases, but lupus has posed a major challenge because of its very heterogeneous presentation. This heterogeneity has led to the creation of several measures of disease activity as well as multiple serologic parameters that also help define disease activity. It’s unrealistic to expect most lupus patients to be in a low disease activity state all the time.
Validation of a reasonable definition of low activity is a great, pragmatic step forward for our field that will help clinicians better care for their patients with systemic lupus erythematosus.
Lisa R. Sammaritano, MD , is a rheumatologist at the Hospital for Special Surgery and Cornell University in New York. She had no disclosures. She made these comments in an interview.
CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.
The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.
The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):
• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.
• No new disease activity.
• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.
• Maintenance on a prednisolone dosage of 7.5 mg/day or less.
• Maintenance on a standard immunosuppressive regimen.
The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).
The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.
The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.
Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.
The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.
SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.
CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.
The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.
The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):
• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.
• No new disease activity.
• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.
• Maintenance on a prednisolone dosage of 7.5 mg/day or less.
• Maintenance on a standard immunosuppressive regimen.
The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).
The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.
The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.
Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.
The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.
SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: A proposed definition of low disease activity in systemic lupus erythematosus received prospective validation.
Major finding: Patients meeting the definition for 9-12 months had an 86% reduced rate of subsequent damage accrual.
Study details: A prospective, multicenter study of 1,735 patients.
Disclosures: The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.
Source: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.
Ablation plus transplant for severe scleroderma shows 11-year benefits
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
CHICAGO – Follow-up out to as long as 11 years from treatment confirmed the long-term efficacy and safety of myeloablative autologous stem cell transplantation for patients with severe scleroderma.
This extended follow-up comprised 43 survivors from the 75 patients originally randomized in a controlled, 6-year trial. Follow-up showed that, among the patients who underwent myeloablation and autologous transplant with hematopoietic stem cells, there were no long-term deaths or cancers, there was an 88% survival rate, and 92% remained off disease-modifying treatment, Keith M. Sullivan, MD, said at the annual meeting of the American College of Rheumatology.
Long-term survival among patients randomized to the study’s control arm, who received treatment with cyclophosphamide, was 53%.
Patients with severe scleroderma with significant internal organ damage who “are improved and off of disease-modifying antirheumatic drugs after 10 or more years from treatment is something new in autoimmune disease,” said Dr. Sullivan, a professor of medicine at Duke University, Durham, N.C.
Based on accumulated data from this randomized trial and other studies, the American Society for Blood and Marrow Transplantation issued a position statement in June 2018 that endorsed autologous hematopoietic stem cell transplantation as “standard of care” for systemic sclerosis (Biol Blood Marrow Transplant. 2018 June 25. doi: 10.1016/j.bbmt.2018.06.025), Dr. Sullivan noted in a video interview.
The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial randomized 75 patients with severe scleroderma and substantial internal organ involvement to receive treatment with either cyclophosphamide or myeloablative radiation followed by immune reconstitution with an autologous hematopoietic stem cell transplant. The trial’s primary endpoint, the global rank composite score at 54 months, showed the superiority of transplantation over standard treatment (N Engl J Med. 2018 Jan 4;378[1]:35-47).
Dr. Sullivan and his associates ran their long-term follow-up study on 43 of these 75 patients (25 from the transplanted group and 18 controls), excluding 21 patients who died during the original study, 4 additional patients from the control arm who died following the end of the original SCOT protocol, and 7 patients either lost to follow-up or who refused to participate in follow-up. Among the 25 transplanted patients, none died during the extended follow-up, 2 experienced cardiac failure, and 23 remained off of any disease-modifying antirheumatic drugs. Among the 18 survivors in the control arm, 3 had cardiac failure, 3 had respiratory failure, and 7 were on treatment with disease-modifying drugs, Dr. Sullivan reported.
In addition, 23 of the 25 (92%) transplanted patients had normal performance status by the Eastern Cooperative Oncology Group criteria, compared with 11 of the 18 controls (61%). A total of 14 (56%) transplant patients were employed, compared with 6 of the 18 controls (33%).
Patients who were transplanted “have their life back, are doing well, and are off treatment,” Dr. Sullivan noted.
Myeloablation and transplant is appropriate for scleroderma patients with significant internal organ involvement, about half of all patients with this disease. The best gauge of severe organ involvement is a pulmonary function test, with a forced vital capacity of 70% or less of predicted as a flag for patients who should consider transplantation, Dr. Sullivan said. He recommended monitoring lung function every 3 months in scleroderma patients because it can deteriorate very suddenly and quickly.
SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
SOURCE: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Survival after 11 years was 88% among transplanted patients and 53% among control patients treated with cyclophosphamide.
Study details: A long-term follow-up of 43 of the 75 patients enrolled in the SCOT trial.
Disclosures: SCOT received no commercial funding. Dr. Sullivan had no disclosures to report.
Source: Sullivan KM et al. ACR Annual Meeting, Abstract 1820.
Multiple interventions boost RA treat-to-target success
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
CHICAGO – A novel disease-management approach that paired routine monitoring of the clinical status of patients with RA and training for their rheumatologists on how to refine their treat-to-target practices led to a modest but meaningful boost in the achievement of treat-to-target goals in a single-center study with 2,549 patients.
After 1 year, patients assigned to the intervention program had a 12% improvement in their treat-to-target implementation score, compared with patients who received standard care, an increase that was “clinically meaningful,” Cianna L. Leatherwood, MD, said while presenting a poster at the annual meeting of the American College of Rheumatology.
This increased score represented improvements in its four components: measuring disease activity, using a disease activity score in treatment decision making, documenting evidence for creating a treatment goal, and making shared decisions, Dr. Leatherwood explained in a video interview. Some of Dr. Leatherwood’s collaborators in this study from Brigham and Women’s Hospital in Boston developed and first introduced the treat-to-target implementation score a few years ago (Arthritis Rheum. 2017 July;69[7]:1374-80).
The major interventions used in this program included having patients complete the Routine Assessment of Patient Index Data 3 index (Rheum Dis Clin North Am. 2009 Nov;35[4]:773-8) at every clinic encounter, focus-group discussions with panels of patients both prior to and during the year-long program, and monthly “learning collaborative sessions” for the nine rheumatologists in the intervention arm to discuss and develop treat-to-target practices, said Dr. Leatherwood, a rheumatologist at Kaiser Permanente in Oakland, Calif. The physicians in the intervention group also received frequent email reminders about adopting a treat-to-target approach. The control arm of the study included 11 rheumatologists who did not participate in these sessions or receive the reminders.
Dr. Leatherwood expressed confidence that other health systems could now adapt and use the treatment model she and her associates developed and tested after tailoring it to better match their local conditions.
The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
SOURCE: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: After 1 year, the treat-to-target implementation score in the intervention patients was 12% higher than among the control patients.
Study details: A single-center, controlled study with 2,549 RA patients and 22 rheumatologists.
Disclosures: The study received partial funding from Pfizer. Dr. Leatherwood had no disclosures to report.
Source: Leatherwood CL et al. ACR Annual Meeting, Abstract 326.
Prior TIA proves less risky than stroke in AF patients
MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.
Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.
“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).
“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”
Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS2 score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA2DS2-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.
To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.
When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
Source: Hacke W et al. World Stroke Congress, Abstract.
MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.
Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.
“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).
“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”
Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS2 score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA2DS2-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.
To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.
When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
Source: Hacke W et al. World Stroke Congress, Abstract.
MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.
Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.
“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).
“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”
Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS2 score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA2DS2-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.
To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.
When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
Source: Hacke W et al. World Stroke Congress, Abstract.
REPORTING FROM THE WORLD STROKE CONGRESS
Key clinical point:
Major finding: The adjusted rate of stroke in patients with a TIA history was not significantly different from patients with no history.
Study details: GARFIELD-AF, a multinational registry of 52,014 patients newly diagnosed with atrial fibrillation.
Disclosures: GARFIELD-AF is funded by Bayer. Dr. Hacke has been an adviser to Boehringer Ingelheim and Cerenovus and he has received research funding from Boehringer Ingelheim.
Source: Hacke W et al. World Stroke Congress, Abstract.
DAPT’s benefit after stroke or TIA clusters in first 21 days
MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.
The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).
The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.
In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.
“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).
Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”
Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.
“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.
POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.
SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.
The new model using data from the POINT trial confirms what had been previously shown in the CHANCE trial – that 21 days is a sensible cutoff for dual antiplatelet treatment for patients immediately following a mild stroke or transient ischemic attack. Treatment with dual antiplatelet therapy for 21 days provides the same added benefit as 90 days of treatment but with less excess bleeding. The new findings confirm that the CHANCE results were not specific to a Chinese population.
For the time being, clopidogrel is the evidence-based antiplatelet drug to pair with aspirin for this indication. Clopidogrel has the advantages of being generic, cheap, available, and familiar. It’s possible that another P2Y12 inhibitor, such as ticagrelor (Brilinta), might work even better, but that needs to be proven to justify the added expense of a brand-name antiplatelet drug.
Mike Sharma, MD , is a stroke neurologist at McMaster University, Hamilton, Ont. He has been an advisor to Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. He made these comments in an interview.
The new model using data from the POINT trial confirms what had been previously shown in the CHANCE trial – that 21 days is a sensible cutoff for dual antiplatelet treatment for patients immediately following a mild stroke or transient ischemic attack. Treatment with dual antiplatelet therapy for 21 days provides the same added benefit as 90 days of treatment but with less excess bleeding. The new findings confirm that the CHANCE results were not specific to a Chinese population.
For the time being, clopidogrel is the evidence-based antiplatelet drug to pair with aspirin for this indication. Clopidogrel has the advantages of being generic, cheap, available, and familiar. It’s possible that another P2Y12 inhibitor, such as ticagrelor (Brilinta), might work even better, but that needs to be proven to justify the added expense of a brand-name antiplatelet drug.
Mike Sharma, MD , is a stroke neurologist at McMaster University, Hamilton, Ont. He has been an advisor to Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. He made these comments in an interview.
The new model using data from the POINT trial confirms what had been previously shown in the CHANCE trial – that 21 days is a sensible cutoff for dual antiplatelet treatment for patients immediately following a mild stroke or transient ischemic attack. Treatment with dual antiplatelet therapy for 21 days provides the same added benefit as 90 days of treatment but with less excess bleeding. The new findings confirm that the CHANCE results were not specific to a Chinese population.
For the time being, clopidogrel is the evidence-based antiplatelet drug to pair with aspirin for this indication. Clopidogrel has the advantages of being generic, cheap, available, and familiar. It’s possible that another P2Y12 inhibitor, such as ticagrelor (Brilinta), might work even better, but that needs to be proven to justify the added expense of a brand-name antiplatelet drug.
Mike Sharma, MD , is a stroke neurologist at McMaster University, Hamilton, Ont. He has been an advisor to Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. He made these comments in an interview.
MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.
The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).
The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.
In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.
“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).
Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”
Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.
“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.
POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.
SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.
MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.
The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).
The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.
In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.
“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).
Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”
Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.
“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.
POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.
SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.
REPORTING FROM THE WORLD STROKE CONGRESS
Key clinical point: All of DAPT’s extra benefit over aspirin alone in recent stroke or transient ischemic attack patients happened during the first 21 days.
Major finding: During the first 21 days, DAPT cut major ischemic events by 35%, compared with aspirin only.
Study details: A prespecified, secondary analysis from POINT, a multicenter, randomized trial with 4,881 patients.
Disclosures: POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm had no disclosures.
Source: Elm JJ et al. World Stroke Congress, Late-breaking session.
Smartphone device beat Holter for post-stroke AF detection
MONTREAL – A smartphone-based method for quick and inexpensive monitoring for atrial fibrillation in patients hospitalized for a recent acute ischemic stroke or transient ischemic attack identified three times more patients with the arrhythmia than did 24-hour Holter monitoring of the same patients after their hospital discharge.
This high level of atrial fibrillation (AF) detection using a relatively cheap and noninvasive device suggests that this method is a good “complement” to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in recent stroke patients, as called for in current guidelines of the world’s cardiology societies.
In the study, 294 of 1,079 patients hospitalized for an acute ischemic stroke or transient ischemic attack (TIA) underwent Holter monitoring, which identified 8 patients (3%) with AF, compared with 25 of these 294 patients (9%) identified with AF while they were hospitalized using serial, 30-second monitoring with the AliveCor device for smartphone assessment of ECG measurement, Bernard Yan, MD, said at the World Stroke Congress. Seven of the eight patients identified with AF by Holter monitoring were also found to have AF by the AliveCor device.
Dr. Yan, an interventional neurologist at the Comprehensive Stroke Center at the Royal Melbourne Hospital, attributed the higher pick-up rate for AF by monitoring during hospitalization to the timing of screening, which was within days of the stroke or TIA, rather than waiting to run a Holter sometime after the patient left the hospital.
“I suspect the difference in timing explains the difference” in detection, he said in an interview. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their ‘hot’ period, right after their stroke.”
The SPOT-AF trial ran at several centers in Australia, China, and Hong Kong, and enrolled 1,079 patients hospitalized for acute ischemic stroke or TIA who all underwent AliveCor monitoring during their median 4-day stay in the hospital. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, usually three or four times a day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician. This 27% incidence of postdischarge Holter monitoring despite guidelines that call for AF screening in all recent ischemic stroke and TIA patients was consistent with a 2016 review of more than 17,000 stroke or TIA patients in Canada that showed 31% underwent 24-hour Holter monitoring for AF during the 30 days following their index event (Stroke. 2016 Aug;47[8]:1982-9).
Although AF screening with a smartphone-based device is inexpensive and easy, Dr. Yan stopped short of suggesting that it is time for this approach to replace a Holter monitor or an implanted loop recorder because that is what current guidelines call for. “To change the guidelines, we need a different study that compares these approaches head to head.”
SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has been a speaker on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.
MONTREAL – A smartphone-based method for quick and inexpensive monitoring for atrial fibrillation in patients hospitalized for a recent acute ischemic stroke or transient ischemic attack identified three times more patients with the arrhythmia than did 24-hour Holter monitoring of the same patients after their hospital discharge.
This high level of atrial fibrillation (AF) detection using a relatively cheap and noninvasive device suggests that this method is a good “complement” to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in recent stroke patients, as called for in current guidelines of the world’s cardiology societies.
In the study, 294 of 1,079 patients hospitalized for an acute ischemic stroke or transient ischemic attack (TIA) underwent Holter monitoring, which identified 8 patients (3%) with AF, compared with 25 of these 294 patients (9%) identified with AF while they were hospitalized using serial, 30-second monitoring with the AliveCor device for smartphone assessment of ECG measurement, Bernard Yan, MD, said at the World Stroke Congress. Seven of the eight patients identified with AF by Holter monitoring were also found to have AF by the AliveCor device.
Dr. Yan, an interventional neurologist at the Comprehensive Stroke Center at the Royal Melbourne Hospital, attributed the higher pick-up rate for AF by monitoring during hospitalization to the timing of screening, which was within days of the stroke or TIA, rather than waiting to run a Holter sometime after the patient left the hospital.
“I suspect the difference in timing explains the difference” in detection, he said in an interview. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their ‘hot’ period, right after their stroke.”
The SPOT-AF trial ran at several centers in Australia, China, and Hong Kong, and enrolled 1,079 patients hospitalized for acute ischemic stroke or TIA who all underwent AliveCor monitoring during their median 4-day stay in the hospital. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, usually three or four times a day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician. This 27% incidence of postdischarge Holter monitoring despite guidelines that call for AF screening in all recent ischemic stroke and TIA patients was consistent with a 2016 review of more than 17,000 stroke or TIA patients in Canada that showed 31% underwent 24-hour Holter monitoring for AF during the 30 days following their index event (Stroke. 2016 Aug;47[8]:1982-9).
Although AF screening with a smartphone-based device is inexpensive and easy, Dr. Yan stopped short of suggesting that it is time for this approach to replace a Holter monitor or an implanted loop recorder because that is what current guidelines call for. “To change the guidelines, we need a different study that compares these approaches head to head.”
SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has been a speaker on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.
MONTREAL – A smartphone-based method for quick and inexpensive monitoring for atrial fibrillation in patients hospitalized for a recent acute ischemic stroke or transient ischemic attack identified three times more patients with the arrhythmia than did 24-hour Holter monitoring of the same patients after their hospital discharge.
This high level of atrial fibrillation (AF) detection using a relatively cheap and noninvasive device suggests that this method is a good “complement” to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in recent stroke patients, as called for in current guidelines of the world’s cardiology societies.
In the study, 294 of 1,079 patients hospitalized for an acute ischemic stroke or transient ischemic attack (TIA) underwent Holter monitoring, which identified 8 patients (3%) with AF, compared with 25 of these 294 patients (9%) identified with AF while they were hospitalized using serial, 30-second monitoring with the AliveCor device for smartphone assessment of ECG measurement, Bernard Yan, MD, said at the World Stroke Congress. Seven of the eight patients identified with AF by Holter monitoring were also found to have AF by the AliveCor device.
Dr. Yan, an interventional neurologist at the Comprehensive Stroke Center at the Royal Melbourne Hospital, attributed the higher pick-up rate for AF by monitoring during hospitalization to the timing of screening, which was within days of the stroke or TIA, rather than waiting to run a Holter sometime after the patient left the hospital.
“I suspect the difference in timing explains the difference” in detection, he said in an interview. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their ‘hot’ period, right after their stroke.”
The SPOT-AF trial ran at several centers in Australia, China, and Hong Kong, and enrolled 1,079 patients hospitalized for acute ischemic stroke or TIA who all underwent AliveCor monitoring during their median 4-day stay in the hospital. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, usually three or four times a day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician. This 27% incidence of postdischarge Holter monitoring despite guidelines that call for AF screening in all recent ischemic stroke and TIA patients was consistent with a 2016 review of more than 17,000 stroke or TIA patients in Canada that showed 31% underwent 24-hour Holter monitoring for AF during the 30 days following their index event (Stroke. 2016 Aug;47[8]:1982-9).
Although AF screening with a smartphone-based device is inexpensive and easy, Dr. Yan stopped short of suggesting that it is time for this approach to replace a Holter monitor or an implanted loop recorder because that is what current guidelines call for. “To change the guidelines, we need a different study that compares these approaches head to head.”
SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has been a speaker on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.
REPORTING FROM THE WORLD STROKE CONGRESS
Key clinical point:
Major finding: Holter monitoring detected atrial fibrillation in 8 of 294 patients, while smartphone monitoring identified 25 with the arrhythmia.
Study details: SPOT-AF, a multicenter study with 1,079 total patients, including 294 who underwent Holter monitoring.
Disclosures: SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has been a speaker on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.
Fat attenuation index boosts coronary CT prognostication
MUNICH – The perivascular fat attenuation index, a new measure of coronary plaque inflammation using data collected by a conventional coronary CT scan, identified an elevated risk for future cardiovascular death that was independent of standard risk factors in both derivation and validation studies with prospective data from more than 3,900 patients.
Patients with a high fat attenuation index (FAI) in the perivascular fat surrounding their right coronary artery had a five- to ninefold higher risk of cardiac mortality during 4-6 years of follow-up than did those with lower scores, after adjustment for conventional risk factors and standard findings from the coronary CT, Charalambos Antoniades, MD, said at the annual congress of the European Society of Cardiology.
The FAI is a “powerful, novel technology for cardiovascular disease risk stratification. It has striking prognostic value for cardiac death and nonfatal MI over and above other risk scores and state-of-the-art interpretation of coronary CT angiography,” said Dr. Antoniades, professor of cardiovascular medicine at the University of Oxford (England). He also highlighted that the data he reported suggested a protective effect in patients with a high FAI who received treatment with aspirin or a statin, and he suggested that FAI might be a way to better target an anti-inflammatory agent such as canakinumab (Ilaris), which showed cardiovascular protective effects in the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Another key feature of the FAI analysis is that it uses data collected by “any standard” coronary CT angiogram, Dr. Antoniades said. He is a founder of, shareholder in, and chief scientific officer of Caristo Diagnostics, the company developing the software that uses coronary CT data to calculate the FAI.
Dr. Antoniades and his associates derived the FAI using data collected from 1,872 patients who underwent planned coronary CT angiography at a clinic in Erlangen, Germany, during 2005-2009. The researchers correlated FAI scores with cardiovascular disease outcomes during a median follow-up of 72 months. They then validated the FAI using data collected from 2,040 patients who underwent a planned coronary CT exam at the Cleveland Clinic during 2008-2016 and then had a median follow-up of 54 months. The researchers called this overall post-hoc analysis of prospectively collected CT and outcomes data the Cardiovascular Risk Prediction using Computed Tomography (CRISP-CT) study.
Using the derivation data, FAI measurements taken from fat around the proximal right coronary artery that met or exceeded the specified cutoff value of –70.1 Hounsfield units were tied to a 9.04-fold greater rate of cardiac death during follow-up, compared with patients with a lower FAI, and after adjustment for several demographic, clinical, and CT-angiography variables. When the researchers ran this analysis using data from the validation patients and the same cutoff value they found that an elevated FAI linked with a 5.6-fold higher rate of cardiac death. Concurrently with Dr. Antoniades’ talk the results appeared in an online article that was later published (Lancet. 2018 Sep 15;392[10151]:929-39).
Calculating a patient’s FAI offers the prospect for “better use of CT information,” Dr. Antoniades said during the discussion of his report. After a coronary CT scan and conventional data processing, about half the patients have no finding that warrants intervention, but about 10% of these patients actually have an inflamed coronary plaque that is at high risk for rupture that could trigger a cardiac event. The FAI provides a way to use coronary CT angiography to identify these at-risk patients, he explained.
MUNICH – The perivascular fat attenuation index, a new measure of coronary plaque inflammation using data collected by a conventional coronary CT scan, identified an elevated risk for future cardiovascular death that was independent of standard risk factors in both derivation and validation studies with prospective data from more than 3,900 patients.
Patients with a high fat attenuation index (FAI) in the perivascular fat surrounding their right coronary artery had a five- to ninefold higher risk of cardiac mortality during 4-6 years of follow-up than did those with lower scores, after adjustment for conventional risk factors and standard findings from the coronary CT, Charalambos Antoniades, MD, said at the annual congress of the European Society of Cardiology.
The FAI is a “powerful, novel technology for cardiovascular disease risk stratification. It has striking prognostic value for cardiac death and nonfatal MI over and above other risk scores and state-of-the-art interpretation of coronary CT angiography,” said Dr. Antoniades, professor of cardiovascular medicine at the University of Oxford (England). He also highlighted that the data he reported suggested a protective effect in patients with a high FAI who received treatment with aspirin or a statin, and he suggested that FAI might be a way to better target an anti-inflammatory agent such as canakinumab (Ilaris), which showed cardiovascular protective effects in the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Another key feature of the FAI analysis is that it uses data collected by “any standard” coronary CT angiogram, Dr. Antoniades said. He is a founder of, shareholder in, and chief scientific officer of Caristo Diagnostics, the company developing the software that uses coronary CT data to calculate the FAI.
Dr. Antoniades and his associates derived the FAI using data collected from 1,872 patients who underwent planned coronary CT angiography at a clinic in Erlangen, Germany, during 2005-2009. The researchers correlated FAI scores with cardiovascular disease outcomes during a median follow-up of 72 months. They then validated the FAI using data collected from 2,040 patients who underwent a planned coronary CT exam at the Cleveland Clinic during 2008-2016 and then had a median follow-up of 54 months. The researchers called this overall post-hoc analysis of prospectively collected CT and outcomes data the Cardiovascular Risk Prediction using Computed Tomography (CRISP-CT) study.
Using the derivation data, FAI measurements taken from fat around the proximal right coronary artery that met or exceeded the specified cutoff value of –70.1 Hounsfield units were tied to a 9.04-fold greater rate of cardiac death during follow-up, compared with patients with a lower FAI, and after adjustment for several demographic, clinical, and CT-angiography variables. When the researchers ran this analysis using data from the validation patients and the same cutoff value they found that an elevated FAI linked with a 5.6-fold higher rate of cardiac death. Concurrently with Dr. Antoniades’ talk the results appeared in an online article that was later published (Lancet. 2018 Sep 15;392[10151]:929-39).
Calculating a patient’s FAI offers the prospect for “better use of CT information,” Dr. Antoniades said during the discussion of his report. After a coronary CT scan and conventional data processing, about half the patients have no finding that warrants intervention, but about 10% of these patients actually have an inflamed coronary plaque that is at high risk for rupture that could trigger a cardiac event. The FAI provides a way to use coronary CT angiography to identify these at-risk patients, he explained.
MUNICH – The perivascular fat attenuation index, a new measure of coronary plaque inflammation using data collected by a conventional coronary CT scan, identified an elevated risk for future cardiovascular death that was independent of standard risk factors in both derivation and validation studies with prospective data from more than 3,900 patients.
Patients with a high fat attenuation index (FAI) in the perivascular fat surrounding their right coronary artery had a five- to ninefold higher risk of cardiac mortality during 4-6 years of follow-up than did those with lower scores, after adjustment for conventional risk factors and standard findings from the coronary CT, Charalambos Antoniades, MD, said at the annual congress of the European Society of Cardiology.
The FAI is a “powerful, novel technology for cardiovascular disease risk stratification. It has striking prognostic value for cardiac death and nonfatal MI over and above other risk scores and state-of-the-art interpretation of coronary CT angiography,” said Dr. Antoniades, professor of cardiovascular medicine at the University of Oxford (England). He also highlighted that the data he reported suggested a protective effect in patients with a high FAI who received treatment with aspirin or a statin, and he suggested that FAI might be a way to better target an anti-inflammatory agent such as canakinumab (Ilaris), which showed cardiovascular protective effects in the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31).
Another key feature of the FAI analysis is that it uses data collected by “any standard” coronary CT angiogram, Dr. Antoniades said. He is a founder of, shareholder in, and chief scientific officer of Caristo Diagnostics, the company developing the software that uses coronary CT data to calculate the FAI.
Dr. Antoniades and his associates derived the FAI using data collected from 1,872 patients who underwent planned coronary CT angiography at a clinic in Erlangen, Germany, during 2005-2009. The researchers correlated FAI scores with cardiovascular disease outcomes during a median follow-up of 72 months. They then validated the FAI using data collected from 2,040 patients who underwent a planned coronary CT exam at the Cleveland Clinic during 2008-2016 and then had a median follow-up of 54 months. The researchers called this overall post-hoc analysis of prospectively collected CT and outcomes data the Cardiovascular Risk Prediction using Computed Tomography (CRISP-CT) study.
Using the derivation data, FAI measurements taken from fat around the proximal right coronary artery that met or exceeded the specified cutoff value of –70.1 Hounsfield units were tied to a 9.04-fold greater rate of cardiac death during follow-up, compared with patients with a lower FAI, and after adjustment for several demographic, clinical, and CT-angiography variables. When the researchers ran this analysis using data from the validation patients and the same cutoff value they found that an elevated FAI linked with a 5.6-fold higher rate of cardiac death. Concurrently with Dr. Antoniades’ talk the results appeared in an online article that was later published (Lancet. 2018 Sep 15;392[10151]:929-39).
Calculating a patient’s FAI offers the prospect for “better use of CT information,” Dr. Antoniades said during the discussion of his report. After a coronary CT scan and conventional data processing, about half the patients have no finding that warrants intervention, but about 10% of these patients actually have an inflamed coronary plaque that is at high risk for rupture that could trigger a cardiac event. The FAI provides a way to use coronary CT angiography to identify these at-risk patients, he explained.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point:
Major finding: Patients with a fat attenuation index at or above the selected cutoff had a five- to ninefold increased rate of cardiac death.
Study details: The CRISP-CT study, which ran a post-hoc analysis of CT angiography data from 3,912 patients.
Disclosures: Dr. Antoniades is a founder of, shareholder in, and chief scientific officer of Caristo Diagnostics, the company developing fat attenuation index software.