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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
Intractable VT halted by noninvasive radiation ablation
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A one-time dose of radiation to arrhythmogenic scars nearly eliminated ventricular tachycardia in five patients who had failed to respond to medical management and, in some cases, catheter ablation.
Major finding: VT episodes were slashed by 99.9% from baseline.
Study details: Case series in 5 patients
Disclosures: The work was funded by the Barnes-Jewish Hospital Foundation, Washington University in St. Louis, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
Source: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773
Novel metabolic biomarkers linked to CHD
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with hazard ratios ranging from 1.09 to 1.13.
Data source: More than 10,000 subjects in the BiomarCaRE consortium.
Disclosures: BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
Faciobrachial dystonic seizures require urgent immunotherapy
SAN DIEGO – The sooner immunotherapy is started for faciobrachial dystonic seizures, the better, according to a retrospective review presented at the American Neurological Association annual meeting.
Only recently described, patients with faciobrachial dystonic seizures (FBDS) have frequent episodes – sometimes hundreds a day – of abrupt, involuntary, stereotypical movements lasting 1-5 seconds and typically involving one half of their face and the arm on the same side, such as a left-sided grimace and arm flex. It’s closely associated with antibodies against leucine-rich glioma, inactivated 1 (LGI-1), a protein that plays a role in synaptic transmission and myelination.
“This is an autoimmune condition. It’s important to get onto it early; you’ve got to treat these seizures with immunotherapy and treat them fast,” she said.
A lot of the time, FBDS is probably mistaken for a movement disorder or tic, but tics aren’t typically dystonic, plus FBDS patients can’t suppress their movements and they don’t feel the buildup of tension, then release typical of tics. “If something doesn’t add up, test for the antibodies,” Dr. Thompson said.
Her team reviewed 103 cases culled from South Korea, Great Britain, Australia, and the United States, the largest cohort assembled to date. The median age was 64 years old; most patients were white, and 62% were men. There were no associations with tumors, and none of the seasonal variation typical of viral causes.
FBDS showed “a striking time-dependent response to immunotherapy. Prompt immunotherapy” stops the seizures and prevents brain damage, “maybe via inhibiting IgG1-mediated complement deposition,” Dr. Thompson said.
Antiepileptic drugs didn’t help much, but immunotherapy did; among patients who had immunotherapy, seizures stopped within 30 days in over half, and in 88% after 3 months. Only one patient with seizure cessation went on to develop cognitive impairment. For every day that immunotherapy was delayed, there was a 0.69% reduction in the probability of stopping the seizures. The window of opportunity appears to be short: among patients whose seizures weren’t terminated within 3 months, 56% progressed to cognitive impairment.
Immunotherapy varied greatly across the study centers, and included intravenous immunoglobulin, azathioprine, and mycophenolate, among other options that were generally given on a background of steroids.
“It became quite obvious that immunotherapy was the key,” but there weren’t enough patients to determine the optimal approach. Dr. Thompson and her colleagues are working to figure that out, as well as what triggers FBDS and its pathophysiology, she said.
Patients who just had seizures had almost exclusively LGI-1 IgG4 antibodies; those who had progressed to cognitive impairment had LGI-1 IgG1 antibodies. It’s unclear at this point what causes the subclass switch as patients progress.
Medial temporal lobe T2-hyperintensities and temporal and frontal lobe ictal EEG changes, as well as serum hyponatremia, were also found almost exclusively in patients with cognitive impairment.
Much remains to be learned about the condition.
There was no industry funding for the work, and Dr. Thompson didn’t have any disclosures.
SAN DIEGO – The sooner immunotherapy is started for faciobrachial dystonic seizures, the better, according to a retrospective review presented at the American Neurological Association annual meeting.
Only recently described, patients with faciobrachial dystonic seizures (FBDS) have frequent episodes – sometimes hundreds a day – of abrupt, involuntary, stereotypical movements lasting 1-5 seconds and typically involving one half of their face and the arm on the same side, such as a left-sided grimace and arm flex. It’s closely associated with antibodies against leucine-rich glioma, inactivated 1 (LGI-1), a protein that plays a role in synaptic transmission and myelination.
“This is an autoimmune condition. It’s important to get onto it early; you’ve got to treat these seizures with immunotherapy and treat them fast,” she said.
A lot of the time, FBDS is probably mistaken for a movement disorder or tic, but tics aren’t typically dystonic, plus FBDS patients can’t suppress their movements and they don’t feel the buildup of tension, then release typical of tics. “If something doesn’t add up, test for the antibodies,” Dr. Thompson said.
Her team reviewed 103 cases culled from South Korea, Great Britain, Australia, and the United States, the largest cohort assembled to date. The median age was 64 years old; most patients were white, and 62% were men. There were no associations with tumors, and none of the seasonal variation typical of viral causes.
FBDS showed “a striking time-dependent response to immunotherapy. Prompt immunotherapy” stops the seizures and prevents brain damage, “maybe via inhibiting IgG1-mediated complement deposition,” Dr. Thompson said.
Antiepileptic drugs didn’t help much, but immunotherapy did; among patients who had immunotherapy, seizures stopped within 30 days in over half, and in 88% after 3 months. Only one patient with seizure cessation went on to develop cognitive impairment. For every day that immunotherapy was delayed, there was a 0.69% reduction in the probability of stopping the seizures. The window of opportunity appears to be short: among patients whose seizures weren’t terminated within 3 months, 56% progressed to cognitive impairment.
Immunotherapy varied greatly across the study centers, and included intravenous immunoglobulin, azathioprine, and mycophenolate, among other options that were generally given on a background of steroids.
“It became quite obvious that immunotherapy was the key,” but there weren’t enough patients to determine the optimal approach. Dr. Thompson and her colleagues are working to figure that out, as well as what triggers FBDS and its pathophysiology, she said.
Patients who just had seizures had almost exclusively LGI-1 IgG4 antibodies; those who had progressed to cognitive impairment had LGI-1 IgG1 antibodies. It’s unclear at this point what causes the subclass switch as patients progress.
Medial temporal lobe T2-hyperintensities and temporal and frontal lobe ictal EEG changes, as well as serum hyponatremia, were also found almost exclusively in patients with cognitive impairment.
Much remains to be learned about the condition.
There was no industry funding for the work, and Dr. Thompson didn’t have any disclosures.
SAN DIEGO – The sooner immunotherapy is started for faciobrachial dystonic seizures, the better, according to a retrospective review presented at the American Neurological Association annual meeting.
Only recently described, patients with faciobrachial dystonic seizures (FBDS) have frequent episodes – sometimes hundreds a day – of abrupt, involuntary, stereotypical movements lasting 1-5 seconds and typically involving one half of their face and the arm on the same side, such as a left-sided grimace and arm flex. It’s closely associated with antibodies against leucine-rich glioma, inactivated 1 (LGI-1), a protein that plays a role in synaptic transmission and myelination.
“This is an autoimmune condition. It’s important to get onto it early; you’ve got to treat these seizures with immunotherapy and treat them fast,” she said.
A lot of the time, FBDS is probably mistaken for a movement disorder or tic, but tics aren’t typically dystonic, plus FBDS patients can’t suppress their movements and they don’t feel the buildup of tension, then release typical of tics. “If something doesn’t add up, test for the antibodies,” Dr. Thompson said.
Her team reviewed 103 cases culled from South Korea, Great Britain, Australia, and the United States, the largest cohort assembled to date. The median age was 64 years old; most patients were white, and 62% were men. There were no associations with tumors, and none of the seasonal variation typical of viral causes.
FBDS showed “a striking time-dependent response to immunotherapy. Prompt immunotherapy” stops the seizures and prevents brain damage, “maybe via inhibiting IgG1-mediated complement deposition,” Dr. Thompson said.
Antiepileptic drugs didn’t help much, but immunotherapy did; among patients who had immunotherapy, seizures stopped within 30 days in over half, and in 88% after 3 months. Only one patient with seizure cessation went on to develop cognitive impairment. For every day that immunotherapy was delayed, there was a 0.69% reduction in the probability of stopping the seizures. The window of opportunity appears to be short: among patients whose seizures weren’t terminated within 3 months, 56% progressed to cognitive impairment.
Immunotherapy varied greatly across the study centers, and included intravenous immunoglobulin, azathioprine, and mycophenolate, among other options that were generally given on a background of steroids.
“It became quite obvious that immunotherapy was the key,” but there weren’t enough patients to determine the optimal approach. Dr. Thompson and her colleagues are working to figure that out, as well as what triggers FBDS and its pathophysiology, she said.
Patients who just had seizures had almost exclusively LGI-1 IgG4 antibodies; those who had progressed to cognitive impairment had LGI-1 IgG1 antibodies. It’s unclear at this point what causes the subclass switch as patients progress.
Medial temporal lobe T2-hyperintensities and temporal and frontal lobe ictal EEG changes, as well as serum hyponatremia, were also found almost exclusively in patients with cognitive impairment.
Much remains to be learned about the condition.
There was no industry funding for the work, and Dr. Thompson didn’t have any disclosures.
AT ANA 2017
Key clinical point:
Major finding: For every day that immunotherapy was delayed, there was a 0.69% reduction in the probability of stopping the seizures and progression to limbic encephalitis and permanent disability.
Data source: Review of 103 patients, the largest cohort assembled to date.
Disclosures: There was no industry funding for the work, and the lead investigator had no disclosures.
Benefit of dabigatran over warfarin persists in AF patient subgroups undergoing PCI
ANAHEIM, CALIF. – The benefit of dabigatran dual therapy versus warfarin triple therapy after percutaneous coronary intervention in patients with atrial fibrillation was consistent whether patients had drug-eluting or bare-metal stents, concomitant treatment with ticagrelor or clopidogrel, or acute coronary syndrome or stable disease as the indication for PCI, according to a subgroup analysis of the RE-DUAL PCI trial.
The trial, presented at the American Heart Association scientific sessions, randomized 2,725 patients to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin – the triple therapy group – or dabigatran 110 mg or 150 mg twice daily plus clopidogrel or ticagrelor – the dual therapy groups (N Engl J Med. 2017 Oct 19;377[16]:1513-24).
After a mean follow-up 14 months, the incidence of the major or clinically relevant nonmajor bleeding was 15.4% in the 110-mg dual-therapy group (hazard ratio, 0.52; 95% CI, 0.42-0.63; P less than .001) and 20.2% in the 150-mg dual-therapy group (HR, 0.72; 95% CI, 0.58-0.88; P less than .001), versus about 26% with triple-therapy.
The incidence of the composite efficacy endpoint – death, unplanned revascularization, myocardial infarction, stroke, or systemic embolism – was 13.7% in the two dual-therapy groups versus 13.4% with triple-therapy (HR, 1.04; 95% CI, 0.84-1.29; P = .005).
The investigators found consistent results when they analyzed their prespecified subgroups.
Drug-eluting stents were placed in 83% of patients; the rest had bare metal stents (BMS). The groups were well-balanced, except BMS patients were again more likely to be new to oral anticoagulation. Bleeding, thromboembolic events, and mortality were consistent with the main results regardless of the stent type, Most of the subjects were on clopidogrel, with just 12% on ticagrelor in both the dabigatran and warfarin groups. Ticagrelor patients were more likely to have ACS as their PCI indication and be new to oral anticoagulation. Ticagrelor patients were also more clinically complex, with a higher bleeding risk. Even so, they had relative bleeding risk reduction and efficacy results with dabigatran that were consistent with the overall finding, Dr. Oldgren said.
Patients were eligible for RE-DUAL PCI (Evaluation of Dual Therapy with Dabigatran vs. Triple Therapy with Warfarin in Patients with AF That Undergo a PCI with Stenting) if they had nonvalvular atrial fibrillation and a successful PCI within 120 hours. Those with bioprosthetic or mechanical heart valves, severe renal insufficiency, or other major comorbidities were excluded.
The trial was funded by Boehringer Ingelheim, the maker of dabigatran. Several investigators were employees. Dr. Oldgren is an adviser to Boehringer Ingelheim. Other authors reported financial ties to the company as well.
ANAHEIM, CALIF. – The benefit of dabigatran dual therapy versus warfarin triple therapy after percutaneous coronary intervention in patients with atrial fibrillation was consistent whether patients had drug-eluting or bare-metal stents, concomitant treatment with ticagrelor or clopidogrel, or acute coronary syndrome or stable disease as the indication for PCI, according to a subgroup analysis of the RE-DUAL PCI trial.
The trial, presented at the American Heart Association scientific sessions, randomized 2,725 patients to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin – the triple therapy group – or dabigatran 110 mg or 150 mg twice daily plus clopidogrel or ticagrelor – the dual therapy groups (N Engl J Med. 2017 Oct 19;377[16]:1513-24).
After a mean follow-up 14 months, the incidence of the major or clinically relevant nonmajor bleeding was 15.4% in the 110-mg dual-therapy group (hazard ratio, 0.52; 95% CI, 0.42-0.63; P less than .001) and 20.2% in the 150-mg dual-therapy group (HR, 0.72; 95% CI, 0.58-0.88; P less than .001), versus about 26% with triple-therapy.
The incidence of the composite efficacy endpoint – death, unplanned revascularization, myocardial infarction, stroke, or systemic embolism – was 13.7% in the two dual-therapy groups versus 13.4% with triple-therapy (HR, 1.04; 95% CI, 0.84-1.29; P = .005).
The investigators found consistent results when they analyzed their prespecified subgroups.
Drug-eluting stents were placed in 83% of patients; the rest had bare metal stents (BMS). The groups were well-balanced, except BMS patients were again more likely to be new to oral anticoagulation. Bleeding, thromboembolic events, and mortality were consistent with the main results regardless of the stent type, Most of the subjects were on clopidogrel, with just 12% on ticagrelor in both the dabigatran and warfarin groups. Ticagrelor patients were more likely to have ACS as their PCI indication and be new to oral anticoagulation. Ticagrelor patients were also more clinically complex, with a higher bleeding risk. Even so, they had relative bleeding risk reduction and efficacy results with dabigatran that were consistent with the overall finding, Dr. Oldgren said.
Patients were eligible for RE-DUAL PCI (Evaluation of Dual Therapy with Dabigatran vs. Triple Therapy with Warfarin in Patients with AF That Undergo a PCI with Stenting) if they had nonvalvular atrial fibrillation and a successful PCI within 120 hours. Those with bioprosthetic or mechanical heart valves, severe renal insufficiency, or other major comorbidities were excluded.
The trial was funded by Boehringer Ingelheim, the maker of dabigatran. Several investigators were employees. Dr. Oldgren is an adviser to Boehringer Ingelheim. Other authors reported financial ties to the company as well.
ANAHEIM, CALIF. – The benefit of dabigatran dual therapy versus warfarin triple therapy after percutaneous coronary intervention in patients with atrial fibrillation was consistent whether patients had drug-eluting or bare-metal stents, concomitant treatment with ticagrelor or clopidogrel, or acute coronary syndrome or stable disease as the indication for PCI, according to a subgroup analysis of the RE-DUAL PCI trial.
The trial, presented at the American Heart Association scientific sessions, randomized 2,725 patients to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin – the triple therapy group – or dabigatran 110 mg or 150 mg twice daily plus clopidogrel or ticagrelor – the dual therapy groups (N Engl J Med. 2017 Oct 19;377[16]:1513-24).
After a mean follow-up 14 months, the incidence of the major or clinically relevant nonmajor bleeding was 15.4% in the 110-mg dual-therapy group (hazard ratio, 0.52; 95% CI, 0.42-0.63; P less than .001) and 20.2% in the 150-mg dual-therapy group (HR, 0.72; 95% CI, 0.58-0.88; P less than .001), versus about 26% with triple-therapy.
The incidence of the composite efficacy endpoint – death, unplanned revascularization, myocardial infarction, stroke, or systemic embolism – was 13.7% in the two dual-therapy groups versus 13.4% with triple-therapy (HR, 1.04; 95% CI, 0.84-1.29; P = .005).
The investigators found consistent results when they analyzed their prespecified subgroups.
Drug-eluting stents were placed in 83% of patients; the rest had bare metal stents (BMS). The groups were well-balanced, except BMS patients were again more likely to be new to oral anticoagulation. Bleeding, thromboembolic events, and mortality were consistent with the main results regardless of the stent type, Most of the subjects were on clopidogrel, with just 12% on ticagrelor in both the dabigatran and warfarin groups. Ticagrelor patients were more likely to have ACS as their PCI indication and be new to oral anticoagulation. Ticagrelor patients were also more clinically complex, with a higher bleeding risk. Even so, they had relative bleeding risk reduction and efficacy results with dabigatran that were consistent with the overall finding, Dr. Oldgren said.
Patients were eligible for RE-DUAL PCI (Evaluation of Dual Therapy with Dabigatran vs. Triple Therapy with Warfarin in Patients with AF That Undergo a PCI with Stenting) if they had nonvalvular atrial fibrillation and a successful PCI within 120 hours. Those with bioprosthetic or mechanical heart valves, severe renal insufficiency, or other major comorbidities were excluded.
The trial was funded by Boehringer Ingelheim, the maker of dabigatran. Several investigators were employees. Dr. Oldgren is an adviser to Boehringer Ingelheim. Other authors reported financial ties to the company as well.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: After a mean follow-up of 14 months, the incidence of major or clinically relevant nonmajor bleeding was 15.4% in the 110-mg dual-therapy group (HR, 0.52; 95% CI, 0.42-0.63, P less than .001) and 20.2% in the 150-mg dual-therapy group (HR, 0.72; 95% CI, 0.58-0.88; P less than .001), versus about 26% with triple-therapy.
Data source: Subgroup analysis of RE-DUAL PCI trial
Disclosures: The trial was funded by Boehringer Ingelheim, the maker of dabigatran. Several investigators were employees. Authors disclosed various financial ties to the company.
Breakthrough cancer gene assay approved, CMS proposes coverage
The Food and Drug Administration approved a new genetic sequencing test that detects mutations across 324 genes in tumor biopsy specimens with an accuracy of 94.6%.
The FoundationOne CDx (F1CDx) test from Foundation Medicine “can identify which patients with any of five tumor types” – non–small-cell lung cancer, melanoma, breast cancer, colorectal cancer, or ovarian cancer – “may benefit from 15 different FDA-approved targeted treatment options,” as well as clinical trial eligibility, “with one test report, avoiding duplicative biopsies,” the agency said in a statement.
On the same day as the approval, the Centers for Medicare & Medicaid Services proposed nationwide coverage for Medicare beneficiaries with recurrent or metastatic disease. CMS is accepting public comments on the proposal for 30 days. The cost of the test is $5,800.
F1CDx went through the FDA and CMS Parallel Review Program, in which the agencies review medical devices concurrently to help reduce the time between approval and Medicare coverage.
F1CDx reads the order of nucleotides on DNA isolated from biopsy specimens to detect a range of genetic anomalies, including base substitutions, insertion and deletion alterations, copy number alterations, and select gene rearrangements, as well as genomic signatures including microsatellite instability and tumor mutational burden. Clinical performance was established by comparing the F1CDx to previously approved tests.
The Food and Drug Administration approved a new genetic sequencing test that detects mutations across 324 genes in tumor biopsy specimens with an accuracy of 94.6%.
The FoundationOne CDx (F1CDx) test from Foundation Medicine “can identify which patients with any of five tumor types” – non–small-cell lung cancer, melanoma, breast cancer, colorectal cancer, or ovarian cancer – “may benefit from 15 different FDA-approved targeted treatment options,” as well as clinical trial eligibility, “with one test report, avoiding duplicative biopsies,” the agency said in a statement.
On the same day as the approval, the Centers for Medicare & Medicaid Services proposed nationwide coverage for Medicare beneficiaries with recurrent or metastatic disease. CMS is accepting public comments on the proposal for 30 days. The cost of the test is $5,800.
F1CDx went through the FDA and CMS Parallel Review Program, in which the agencies review medical devices concurrently to help reduce the time between approval and Medicare coverage.
F1CDx reads the order of nucleotides on DNA isolated from biopsy specimens to detect a range of genetic anomalies, including base substitutions, insertion and deletion alterations, copy number alterations, and select gene rearrangements, as well as genomic signatures including microsatellite instability and tumor mutational burden. Clinical performance was established by comparing the F1CDx to previously approved tests.
The Food and Drug Administration approved a new genetic sequencing test that detects mutations across 324 genes in tumor biopsy specimens with an accuracy of 94.6%.
The FoundationOne CDx (F1CDx) test from Foundation Medicine “can identify which patients with any of five tumor types” – non–small-cell lung cancer, melanoma, breast cancer, colorectal cancer, or ovarian cancer – “may benefit from 15 different FDA-approved targeted treatment options,” as well as clinical trial eligibility, “with one test report, avoiding duplicative biopsies,” the agency said in a statement.
On the same day as the approval, the Centers for Medicare & Medicaid Services proposed nationwide coverage for Medicare beneficiaries with recurrent or metastatic disease. CMS is accepting public comments on the proposal for 30 days. The cost of the test is $5,800.
F1CDx went through the FDA and CMS Parallel Review Program, in which the agencies review medical devices concurrently to help reduce the time between approval and Medicare coverage.
F1CDx reads the order of nucleotides on DNA isolated from biopsy specimens to detect a range of genetic anomalies, including base substitutions, insertion and deletion alterations, copy number alterations, and select gene rearrangements, as well as genomic signatures including microsatellite instability and tumor mutational burden. Clinical performance was established by comparing the F1CDx to previously approved tests.
Aim for BP a bit above SPRINT
ANAHEIM – If blood pressure isn’t measured the way it was in the SPRINT trial, it shouldn’t be treated all the way down to the SPRINT target of less than 120 mm Hg; it’s best to aim a little higher, according to investigators from Kaiser Permanente of Northern California.
SPRINT (the Systolic Blood Pressure Intervention Trial) found that treating hypertension to below 120 mm Hg – as opposed to below 140 mm Hg – reduced the risk of cardiovascular events and death, but blood pressure wasn’t measured the way it usually is in standard practice. Among other differences, SPRINT subjects rested for 5 minutes beforehand, sometimes unobserved, and then three automated measurements were taken and averaged (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
In a review of 73,522 hypertensive patients, the Kaiser investigators found that those treated to a mean systolic BP (SBP) of 122 mm Hg – based on standard office measurement – actually had worse outcomes than did those treated to a mean of 132 mm Hg, with a greater incidence of cardiovascular events, hypotension, electrolyte abnormalities, and other problems.
“The way SPRINT measured BP was systematically different than the BPs we rely on to treat patients in clinical practice. We think that, unless you are going to implement a SPRINT-like protocol, aiming for a slightly higher target of around a mean of 130-132 mm Hg will achieve optimal outcomes. You are likely achieving a SPRINT BP of around 120-125 mm Hg,” said Alan Go, MD, director of the comprehensive clinical research unit at Kaiser Permanente of Northern California, Oakland.
Meanwhile, “if you [treat] to 120 mm Hg, you are probably getting around a SPRINT 114 mm Hg. That runs the risk of hypotension, which we did see. There is also the potential for coronary ischemia because you are no longer providing adequate coronary perfusion,” he said at the American Heart Association scientific sessions.
In their “SPRINT to translation” study, Dr. Go and his team reviewed Kaiser’s electronic medical records to identify patients with baseline BPs of 130-180 mm Hg who met SPRINT criteria and then evaluated how they fared over about 6 years of blood pressure management, with at least one BP taken every 6 months; 7,213 patients were treated to an SBP of 140-149 mm Hg and a mean of 143 mm Hg; 44,847 were treated to an SBP of 126-139 mm Hg and a mean of 132 mm Hg; and 21,462 were treated to 115-125 mm Hg and a mean of 122 mm Hg.
After extensive adjustment for potential confounders, patients treated to 140-149 mm Hg, versus those treated to 126-139 mm Hg, had a 70% increased risk of the composite outcome of acute MI, unstable angina, heart failure, stroke, and cardiovascular death, and a 28% increased risk of all-cause mortality. They also had an increased risk of acute kidney injury, electrolyte abnormalities, and other problems.
More surprisingly, patients treated to 115-125 mm Hg, again versus those treated to 126-139 mm Hg, also had an increased risk of the composite outcome of 9%. They had lower rates of MI and ischemic stroke, but higher rates of heart failure and cardiovascular death. There was also a 17% increased risk of acute kidney injury and a 51% increased risk of hypotension requiring ED or hospital treatment, as well as more electrolyte abnormalities.
The 115-125 mm Hg group also had a 48% increased risk of all-cause mortality. The magnitude of the increase suggests that low blood pressure was a secondary effect of terminal illness in some cases, but Dr. Go didn’t think that was the entire explanation.
The participants had a mean age of 70 years; 63% were women and 75% were white. As in SPRINT, patients with baseline heart failure, stroke, systolic dysfunction, diabetes, end-stage renal disease, and cancer were among those excluded.
There was no external funding for the work, and the investigators didn’t have any disclosures.
ANAHEIM – If blood pressure isn’t measured the way it was in the SPRINT trial, it shouldn’t be treated all the way down to the SPRINT target of less than 120 mm Hg; it’s best to aim a little higher, according to investigators from Kaiser Permanente of Northern California.
SPRINT (the Systolic Blood Pressure Intervention Trial) found that treating hypertension to below 120 mm Hg – as opposed to below 140 mm Hg – reduced the risk of cardiovascular events and death, but blood pressure wasn’t measured the way it usually is in standard practice. Among other differences, SPRINT subjects rested for 5 minutes beforehand, sometimes unobserved, and then three automated measurements were taken and averaged (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
In a review of 73,522 hypertensive patients, the Kaiser investigators found that those treated to a mean systolic BP (SBP) of 122 mm Hg – based on standard office measurement – actually had worse outcomes than did those treated to a mean of 132 mm Hg, with a greater incidence of cardiovascular events, hypotension, electrolyte abnormalities, and other problems.
“The way SPRINT measured BP was systematically different than the BPs we rely on to treat patients in clinical practice. We think that, unless you are going to implement a SPRINT-like protocol, aiming for a slightly higher target of around a mean of 130-132 mm Hg will achieve optimal outcomes. You are likely achieving a SPRINT BP of around 120-125 mm Hg,” said Alan Go, MD, director of the comprehensive clinical research unit at Kaiser Permanente of Northern California, Oakland.
Meanwhile, “if you [treat] to 120 mm Hg, you are probably getting around a SPRINT 114 mm Hg. That runs the risk of hypotension, which we did see. There is also the potential for coronary ischemia because you are no longer providing adequate coronary perfusion,” he said at the American Heart Association scientific sessions.
In their “SPRINT to translation” study, Dr. Go and his team reviewed Kaiser’s electronic medical records to identify patients with baseline BPs of 130-180 mm Hg who met SPRINT criteria and then evaluated how they fared over about 6 years of blood pressure management, with at least one BP taken every 6 months; 7,213 patients were treated to an SBP of 140-149 mm Hg and a mean of 143 mm Hg; 44,847 were treated to an SBP of 126-139 mm Hg and a mean of 132 mm Hg; and 21,462 were treated to 115-125 mm Hg and a mean of 122 mm Hg.
After extensive adjustment for potential confounders, patients treated to 140-149 mm Hg, versus those treated to 126-139 mm Hg, had a 70% increased risk of the composite outcome of acute MI, unstable angina, heart failure, stroke, and cardiovascular death, and a 28% increased risk of all-cause mortality. They also had an increased risk of acute kidney injury, electrolyte abnormalities, and other problems.
More surprisingly, patients treated to 115-125 mm Hg, again versus those treated to 126-139 mm Hg, also had an increased risk of the composite outcome of 9%. They had lower rates of MI and ischemic stroke, but higher rates of heart failure and cardiovascular death. There was also a 17% increased risk of acute kidney injury and a 51% increased risk of hypotension requiring ED or hospital treatment, as well as more electrolyte abnormalities.
The 115-125 mm Hg group also had a 48% increased risk of all-cause mortality. The magnitude of the increase suggests that low blood pressure was a secondary effect of terminal illness in some cases, but Dr. Go didn’t think that was the entire explanation.
The participants had a mean age of 70 years; 63% were women and 75% were white. As in SPRINT, patients with baseline heart failure, stroke, systolic dysfunction, diabetes, end-stage renal disease, and cancer were among those excluded.
There was no external funding for the work, and the investigators didn’t have any disclosures.
ANAHEIM – If blood pressure isn’t measured the way it was in the SPRINT trial, it shouldn’t be treated all the way down to the SPRINT target of less than 120 mm Hg; it’s best to aim a little higher, according to investigators from Kaiser Permanente of Northern California.
SPRINT (the Systolic Blood Pressure Intervention Trial) found that treating hypertension to below 120 mm Hg – as opposed to below 140 mm Hg – reduced the risk of cardiovascular events and death, but blood pressure wasn’t measured the way it usually is in standard practice. Among other differences, SPRINT subjects rested for 5 minutes beforehand, sometimes unobserved, and then three automated measurements were taken and averaged (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
In a review of 73,522 hypertensive patients, the Kaiser investigators found that those treated to a mean systolic BP (SBP) of 122 mm Hg – based on standard office measurement – actually had worse outcomes than did those treated to a mean of 132 mm Hg, with a greater incidence of cardiovascular events, hypotension, electrolyte abnormalities, and other problems.
“The way SPRINT measured BP was systematically different than the BPs we rely on to treat patients in clinical practice. We think that, unless you are going to implement a SPRINT-like protocol, aiming for a slightly higher target of around a mean of 130-132 mm Hg will achieve optimal outcomes. You are likely achieving a SPRINT BP of around 120-125 mm Hg,” said Alan Go, MD, director of the comprehensive clinical research unit at Kaiser Permanente of Northern California, Oakland.
Meanwhile, “if you [treat] to 120 mm Hg, you are probably getting around a SPRINT 114 mm Hg. That runs the risk of hypotension, which we did see. There is also the potential for coronary ischemia because you are no longer providing adequate coronary perfusion,” he said at the American Heart Association scientific sessions.
In their “SPRINT to translation” study, Dr. Go and his team reviewed Kaiser’s electronic medical records to identify patients with baseline BPs of 130-180 mm Hg who met SPRINT criteria and then evaluated how they fared over about 6 years of blood pressure management, with at least one BP taken every 6 months; 7,213 patients were treated to an SBP of 140-149 mm Hg and a mean of 143 mm Hg; 44,847 were treated to an SBP of 126-139 mm Hg and a mean of 132 mm Hg; and 21,462 were treated to 115-125 mm Hg and a mean of 122 mm Hg.
After extensive adjustment for potential confounders, patients treated to 140-149 mm Hg, versus those treated to 126-139 mm Hg, had a 70% increased risk of the composite outcome of acute MI, unstable angina, heart failure, stroke, and cardiovascular death, and a 28% increased risk of all-cause mortality. They also had an increased risk of acute kidney injury, electrolyte abnormalities, and other problems.
More surprisingly, patients treated to 115-125 mm Hg, again versus those treated to 126-139 mm Hg, also had an increased risk of the composite outcome of 9%. They had lower rates of MI and ischemic stroke, but higher rates of heart failure and cardiovascular death. There was also a 17% increased risk of acute kidney injury and a 51% increased risk of hypotension requiring ED or hospital treatment, as well as more electrolyte abnormalities.
The 115-125 mm Hg group also had a 48% increased risk of all-cause mortality. The magnitude of the increase suggests that low blood pressure was a secondary effect of terminal illness in some cases, but Dr. Go didn’t think that was the entire explanation.
The participants had a mean age of 70 years; 63% were women and 75% were white. As in SPRINT, patients with baseline heart failure, stroke, systolic dysfunction, diabetes, end-stage renal disease, and cancer were among those excluded.
There was no external funding for the work, and the investigators didn’t have any disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Cardiovascular events were 9% more likely in patients treated to 115-125 mm Hg vs. those treated to 126-139 mm Hg.
Data source: Review of 73,522 hypertensive patients at Kaiser Permanente of Northern California
Disclosures: There was no external funding for the work, and the investigators had no disclosures.
Observing BP measurement made no difference in SPRINT
ANAHEIM, CALIF. – More than half of the BP measurements of patients in the SPRINT trial were at least partially attended by clinic staff, but those efforts made no difference in outcomes, according to a survey presented by SPRINT investigators at the American Heart Association scientific sessions.
“It really didn’t matter” whether measurements were observed or not; blood pressure control and outcomes – fewer deaths and cardiovascular events when hypertension was treated to below 120 mm Hg instead of below 140 mm Hg – were largely the same either way, said the survey’s lead investigator Karen C. Johnson, MD, professor of women’s health and preventive medicine at the University of Tennessee in Memphis. 
What did matter were the other measures SPRINT [Systolic Blood Pressure Intervention Trial] took to ensure accurate blood pressure measurement, including patients resting for 5 minutes; three automated readings taken afterward then averaged; proper cuff size; feet flat on the floor while patients sat; arms at proper level, and no talking, texting, or filling out forms during the reading, Dr. Johnson said (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
“If you do [those things], then it doesn’t matter if somebody is in the room or not; you can treat to the levels we are talking about,” said William Cushman, MD, professor of medicine and physiology at the university, and also a SPRINT investigator. 
Although the SPRINT researchers hadn’t addressed the issue before the AHA meeting, it’s been widely thought, and even reported in some places, that blood pressures in the trial were unattended. The misperception has led to anxiety about how to apply SPRINT to everyday practice, since few clinics are set up to have patients sit alone for 5 or 10 minutes for a blood pressure.
To address the concern, the SPRINT team surveyed study sites after the trial ended. It turned out that 4,082 subjects were at sites where patients were usually left alone for both the 5-minute rest period and the three BP readings, and 2,247 were at sites where staff usually attended both; 1,746 were at sites that left patients alone for the rest period only; and 570 were at sites where patients were alone only for the BP readings.
Observation had no impact on blood pressure. In the intensive arm, participants achieved and maintained an average systolic BP of about 120 mm Hg in all four groups. In the standard treatment arm, that average was about 135 mm Hg in all four groups. “When we look at the number of medications used, they were very similar in all four blood pressure groups,” with intensive treatment patients taking an average of one extra drug, Dr. Johnson said.
Intensive treatment, versus standard treatment, reduced cardiovascular events to a similar extent in patients who were alone for the entire blood pressure reading (by 38%) and those who were accompanied throughout (by 36%). For reasons that are not clear, intensive treatment did not significantly reduce risk among subjects who were observed during rest or observed for blood pressure readings. Both groups had lower Framingham 10-year cardiovascular disease risk scores, which may have been a confounder.
Meanwhile, the rate of adverse events and total mortality – lower with intensive treatment – did not vary by observation, Dr. Johnson said.
The survey excluded 716 subjects at 14 study sites who could not be classified into one of the four BP observation categories.
SPRINT was sponsored by the National Institutes of Health. Doctors Johnson and Cushman didn’t have any disclosures.
ANAHEIM, CALIF. – More than half of the BP measurements of patients in the SPRINT trial were at least partially attended by clinic staff, but those efforts made no difference in outcomes, according to a survey presented by SPRINT investigators at the American Heart Association scientific sessions.
“It really didn’t matter” whether measurements were observed or not; blood pressure control and outcomes – fewer deaths and cardiovascular events when hypertension was treated to below 120 mm Hg instead of below 140 mm Hg – were largely the same either way, said the survey’s lead investigator Karen C. Johnson, MD, professor of women’s health and preventive medicine at the University of Tennessee in Memphis.
What did matter were the other measures SPRINT [Systolic Blood Pressure Intervention Trial] took to ensure accurate blood pressure measurement, including patients resting for 5 minutes; three automated readings taken afterward then averaged; proper cuff size; feet flat on the floor while patients sat; arms at proper level, and no talking, texting, or filling out forms during the reading, Dr. Johnson said (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
“If you do [those things], then it doesn’t matter if somebody is in the room or not; you can treat to the levels we are talking about,” said William Cushman, MD, professor of medicine and physiology at the university, and also a SPRINT investigator.
Although the SPRINT researchers hadn’t addressed the issue before the AHA meeting, it’s been widely thought, and even reported in some places, that blood pressures in the trial were unattended. The misperception has led to anxiety about how to apply SPRINT to everyday practice, since few clinics are set up to have patients sit alone for 5 or 10 minutes for a blood pressure.
To address the concern, the SPRINT team surveyed study sites after the trial ended. It turned out that 4,082 subjects were at sites where patients were usually left alone for both the 5-minute rest period and the three BP readings, and 2,247 were at sites where staff usually attended both; 1,746 were at sites that left patients alone for the rest period only; and 570 were at sites where patients were alone only for the BP readings.
Observation had no impact on blood pressure. In the intensive arm, participants achieved and maintained an average systolic BP of about 120 mm Hg in all four groups. In the standard treatment arm, that average was about 135 mm Hg in all four groups. “When we look at the number of medications used, they were very similar in all four blood pressure groups,” with intensive treatment patients taking an average of one extra drug, Dr. Johnson said.
Intensive treatment, versus standard treatment, reduced cardiovascular events to a similar extent in patients who were alone for the entire blood pressure reading (by 38%) and those who were accompanied throughout (by 36%). For reasons that are not clear, intensive treatment did not significantly reduce risk among subjects who were observed during rest or observed for blood pressure readings. Both groups had lower Framingham 10-year cardiovascular disease risk scores, which may have been a confounder.
Meanwhile, the rate of adverse events and total mortality – lower with intensive treatment – did not vary by observation, Dr. Johnson said.
The survey excluded 716 subjects at 14 study sites who could not be classified into one of the four BP observation categories.
SPRINT was sponsored by the National Institutes of Health. Doctors Johnson and Cushman didn’t have any disclosures.
ANAHEIM, CALIF. – More than half of the BP measurements of patients in the SPRINT trial were at least partially attended by clinic staff, but those efforts made no difference in outcomes, according to a survey presented by SPRINT investigators at the American Heart Association scientific sessions.
“It really didn’t matter” whether measurements were observed or not; blood pressure control and outcomes – fewer deaths and cardiovascular events when hypertension was treated to below 120 mm Hg instead of below 140 mm Hg – were largely the same either way, said the survey’s lead investigator Karen C. Johnson, MD, professor of women’s health and preventive medicine at the University of Tennessee in Memphis.
What did matter were the other measures SPRINT [Systolic Blood Pressure Intervention Trial] took to ensure accurate blood pressure measurement, including patients resting for 5 minutes; three automated readings taken afterward then averaged; proper cuff size; feet flat on the floor while patients sat; arms at proper level, and no talking, texting, or filling out forms during the reading, Dr. Johnson said (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
“If you do [those things], then it doesn’t matter if somebody is in the room or not; you can treat to the levels we are talking about,” said William Cushman, MD, professor of medicine and physiology at the university, and also a SPRINT investigator.
Although the SPRINT researchers hadn’t addressed the issue before the AHA meeting, it’s been widely thought, and even reported in some places, that blood pressures in the trial were unattended. The misperception has led to anxiety about how to apply SPRINT to everyday practice, since few clinics are set up to have patients sit alone for 5 or 10 minutes for a blood pressure.
To address the concern, the SPRINT team surveyed study sites after the trial ended. It turned out that 4,082 subjects were at sites where patients were usually left alone for both the 5-minute rest period and the three BP readings, and 2,247 were at sites where staff usually attended both; 1,746 were at sites that left patients alone for the rest period only; and 570 were at sites where patients were alone only for the BP readings.
Observation had no impact on blood pressure. In the intensive arm, participants achieved and maintained an average systolic BP of about 120 mm Hg in all four groups. In the standard treatment arm, that average was about 135 mm Hg in all four groups. “When we look at the number of medications used, they were very similar in all four blood pressure groups,” with intensive treatment patients taking an average of one extra drug, Dr. Johnson said.
Intensive treatment, versus standard treatment, reduced cardiovascular events to a similar extent in patients who were alone for the entire blood pressure reading (by 38%) and those who were accompanied throughout (by 36%). For reasons that are not clear, intensive treatment did not significantly reduce risk among subjects who were observed during rest or observed for blood pressure readings. Both groups had lower Framingham 10-year cardiovascular disease risk scores, which may have been a confounder.
Meanwhile, the rate of adverse events and total mortality – lower with intensive treatment – did not vary by observation, Dr. Johnson said.
The survey excluded 716 subjects at 14 study sites who could not be classified into one of the four BP observation categories.
SPRINT was sponsored by the National Institutes of Health. Doctors Johnson and Cushman didn’t have any disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Blood pressure and CV event reductions were similar in the 4,082 subjects at sites where patients were usually left alone for both the 5-minute rest period and the three BP readings, the 2,247 patients at sites where staff usually attended both, the 1,746 at sites that left patients alone for the rest period only, and the 570 at sites where patients were alone only for the BP readings.
Data source: A survey of SPRINT study sites.
Disclosures: SPRINT was sponsored by the National Institutes of Health. The presenter had no disclosures.
Restrictive transfusion strategy safe in cardiac surgery
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Overall, 11.4% in the restrictive-threshold group, versus 12.5% in the liberal-threshold group, met the study’s composite primary outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis.
Data source: TRICS III, a randomized, noninferiority trial with almost 5,000 participants
Disclosures: TRICS III was funded by the Canadian Institutes of Health Research, among others. The lead investigator reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
Keep PCI patients on aspirin for noncardiac surgery
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds.
Data source: POISE-2, a randomized trial of 470 PCI patients.
Disclosures: The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. The lead investigator has no industry disclosures.
ACA repeal could mean financial ruin for many MI, stroke patients
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
ANAHEIM, CALIF. – Before the Affordable Care Act, over 1 in 8 people under 60 years old hospitalized for acute myocardial infarction or stroke had no insurance, and it ruined most of them financially, according to an analysis presented at the American Heart Association scientific sessions.
The importance of the study is that it shows what could happen if the ACA goes away. Debate over its future is “all about pushing people off insurance.” Plans floated in early 2017 “would have increased the uninsured rate to 49 million people,” said lead investigators Rohan Khera, MD, a cardiology fellow at the University of Texas Southwestern Medical Center, Dallas.
And even under the ACA, there are still about 27 million people in the United States, about 8.6% of the population, who don’t have health insurance. Although that’s down from about 44 million people (14.5%) before the ACA, a considerable number of people still face financial ruin if they have a serious medical problem. “Until there is universal coverage for those without resources, catastrophic illness will remain a disabling financial threat to many Americans,” Dr. Khera said.
In a review of the National Inpatient Sample, the investigators identified 39,296 acute myocardial infarction (AMI) and 29,182 stroke hospitalizations among people aged 18-60 years with no insurance from 2008 to 2012, which corresponded to 188,192 AMI and 139,687 stroke hospitalizations nationwide. Overall, the uninsured made up 15% of AMI and stroke hospitalizations among the nonelderly.
By using U.S. Census data to estimate annual income, and U.S. Bureau of Labor Statistics data to estimate food costs, the team found that the median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects. The median stroke bill – $31,218 – exceeded 40% of what was left over after food in 75%. The situation was deemed “catastrophic” in both instances.
It’s true that hospitalization costs might have been reduced or waived in some cases, but the analysis did not consider missed work, disability, and outpatient costs. If anything, the financial burden on the uninsured was underestimated, Dr. Khera said.
The work was funded by the National Institutes of Health, and published in Circulation (2018 Nov 13. doi: 10.1161/CIRCULATIONAHA.117.030128) to coincide with the presentation. Dr. Khera had no disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: The median hospital charge for AMI – $53,384 – exceeded 40% of the annual income left after food costs in 85% of uninsured subjects.
Data source: Modeling study using the National Impatient Sample, U.S. Census data, and U.S. Bureau of Labor Statistics data.
Disclosures: The work was funded by the National Institutes of Health. The lead investigator didn’t have any disclosures.