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CTPA overused in veterans with suspected PE
SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.
A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.
Therefore, CTPA was overused.
Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.
She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.
She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.
A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.
Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.
Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.
SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.
A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.
Therefore, CTPA was overused.
Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.
She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.
She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.
A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.
Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.
Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.
SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.
A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.
Therefore, CTPA was overused.
Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.
She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.
She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.
A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.
Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.
Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.
Obese PE patients have lower risk of death
SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.
The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”
Dr. Khan discussed this result in a presentation at CHEST 2018.
Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.
His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).
The obese PE patients were more often female, black, and younger than 65 years of age.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.
The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.
“I think it’s a rich area for more and further research, especially in basic science,” he added.
Dr. Khan and his coauthors said they had no relationships relevant to the study.
SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.
The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”
Dr. Khan discussed this result in a presentation at CHEST 2018.
Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.
His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).
The obese PE patients were more often female, black, and younger than 65 years of age.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.
The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.
“I think it’s a rich area for more and further research, especially in basic science,” he added.
Dr. Khan and his coauthors said they had no relationships relevant to the study.
SAN ANTONIO—Patients with pulmonary embolism (PE) have a lower mortality risk if they are obese, according to a retrospective analysis of nearly 2 million PE discharges.
The obese patients had a lower mortality risk despite receiving more thrombolytics and mechanical intubation, said study investigator Zubair Khan, MD, of the University of Toledo Medical Center in Ohio.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said. “When we initiated the study, we did not expect this result.”
Dr. Khan discussed this result in a presentation at CHEST 2018.
Dr. Khan noted that the association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions, including stable heart failure, coronary artery disease, unstable angina, myocardial infarction, and also in some PE studies.
His team’s study, conducted using the National Inpatient Sample database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. The researchers included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P<0.001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P<0.001), as was chronic lung disease and chronic liver disease.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P<0.001) and mechanical ventilation (5.8% vs. 4%; P<0.001), and they more frequently had cardiogenic shock (0.65% vs. 0.45%; P<0.001).
The obese PE patients were more often female, black, and younger than 65 years of age.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014.
The lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan said.
“I think it’s a rich area for more and further research, especially in basic science,” he added.
Dr. Khan and his coauthors said they had no relationships relevant to the study.
Be proactive with prophylaxis to tame VTE
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
Venous thromboembolism (VTE) is the No. 1 cause of preventable deaths in hospitals, and 60% of all VTE cases occur during or following hospitalization, according to Jeffrey I. Weitz, MD, of McMaster University in Hamilton, Ont.
, he said in a webinar to promote World Thrombosis Day.
“To prevent VTE, people need to be aware of the problem,” he said. Hospitalization for any reason increases the risk of VTE, but thromboprophylaxis may be underused in medical patients, compared with surgical patients, because most surgical patients are automatically considered at risk.
Prevention of VTE involves understanding the risk factors, Dr. Weitz said. He pointed to a triad of conditions that promote clotting: slow blood flow, injury to the vessel wall, and increased clotability of the blood.
In a study of VTE risk factors, recent surgery with hospitalization and trauma topped the list, but hospitalization without recent surgery was associated with a nearly 8-fold increase in risk (Arch Intern Med. 2000;160[6]:809-15).
Evidence supports the value of anticoagulant prophylaxis, Dr. Weitz said. In a 2007 meta-analysis, use of anticoagulants reduced the risk of VTE by approximately 60% (Ann Intern Med. 2007 Feb 20;146[4]:278-88), and a 2011 update showed a reduction in risk of approximately 30% (Ann Intern Med. 2011 Nov 1;155[9]:602-15).
While risk assessment remains a challenge, several models can help, said Dr. Weitz.
Current guidelines from the American College of Chest Physicians suggest a shift toward individualized assessment of VTE risk, and the Centers for Medicare & Medicaid Services mandates VTE risk assessment, Dr. Weitz said.
He offered seven steps to improve prophylaxis in the hospital:
1. Obtain commitment from hospital leadership, including formation of a committee.
2. Have a written hospital policy on thromboprophylaxis.
3. Keep the policy simple and standard in terms of who gets prophylaxis and when.
4. Use order sets, computer order entry, and decision support.
5. Make the prophylaxis decision mandatory.
6. Involve of all the members of the care team and patients.
7. Use audits to measure improvement.
Several risk assessment models for VTE in hospitalized medical patients have been studied, including the Padua and IMPROVE models, Dr. Weitz said. For any model, factoring in the D-dimer can provide more information. “If D-dimer is increased more than twice the upper limit of normal, it is a risk factor for VTE,” he said.
Another consideration in thromboprophylaxis involves extending the duration of prophylaxis beyond the hospital stay, which is becoming a larger issue because of the pressure to move patients out of the hospital as quickly as possible, Dr. Weitz said. However, trials of extended thromboprophylaxis have yielded mixed results. Extended doses of medications, including rivaroxaban, enoxaparin, apixaban, and betrixaban can reduce the risk of VTE, but can also increase the risk of major bleeding.
“I think at this point we are not yet there at identifying patients who should have thromboprophylaxis beyond the hospital stay,” Dr. Weitz said.
But VTE risk should be assessed in all hospitalized patients, and “appropriate thromboprophylaxis is essential for reducing the burden of hospital-associated VTE,” he said.
Dr. Weitz encouraged clinicians to explore more resources for managing VTE risk at worldthrombosisday.org.
Dr. Weitz reported relationships with companies including Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Ionis Pharmaceuticals, Janssen, Merck, Novartis, and Servier. He also reported research support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Canadian Fund for Innovation.
FROM WORLD THROMBOSIS DAY 2018 WEBINAR
Rivaroxaban gains indication for prevention of major cardiovascular events in CAD/PAD
when taken with aspirin, Janssen Pharmaceuticals announced on October 11.
The Food and Drug Administration’s approval was based on a review of the 27,000-patient COMPASS trial, which showed last year that a low dosage of rivaroxaban (Xarelto) plus aspirin reduced the combined rate of cardiovascular disease events by 24% in patients with coronary artery disease and by 28% in participants with peripheral artery disease, compared with aspirin alone. (N Engl J Med. 2017 Oct 5;377[14]:1319-30)
The flip side to the reduction in COMPASS’s combined primary endpoint was a 51% increase in major bleeding. However, that bump did not translate to increases in fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) studied two dosages of rivaroxaban, 2.5 mg and 5 mg twice daily, and it was the lower dosage that did the trick. Until this approval, that formulation wasn’t available; Janssen announced the coming of the 2.5-mg pill in its release.
The new prescribing information states specifically that Xarelto 2.5 mg is indicated, in combination with aspirin, to reduce the risk of major cardiovascular events, cardiovascular death, MI, and stroke in patients with chronic coronary artery disease or peripheral artery disease.
This is the sixth indication for rivaroxaban, a factor Xa inhibitor that was first approved in 2011. It is also the first indication for cardiovascular prevention for any factor Xa inhibitor. Others on the U.S. market are apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa).
COMPASS was presented at the 2017 annual congress of the European Society of Cardiology. At that time, Eugene Braunwald, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, commented that the trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease.” He added that the results are “an important step for thrombocardiology.”
when taken with aspirin, Janssen Pharmaceuticals announced on October 11.
The Food and Drug Administration’s approval was based on a review of the 27,000-patient COMPASS trial, which showed last year that a low dosage of rivaroxaban (Xarelto) plus aspirin reduced the combined rate of cardiovascular disease events by 24% in patients with coronary artery disease and by 28% in participants with peripheral artery disease, compared with aspirin alone. (N Engl J Med. 2017 Oct 5;377[14]:1319-30)
The flip side to the reduction in COMPASS’s combined primary endpoint was a 51% increase in major bleeding. However, that bump did not translate to increases in fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) studied two dosages of rivaroxaban, 2.5 mg and 5 mg twice daily, and it was the lower dosage that did the trick. Until this approval, that formulation wasn’t available; Janssen announced the coming of the 2.5-mg pill in its release.
The new prescribing information states specifically that Xarelto 2.5 mg is indicated, in combination with aspirin, to reduce the risk of major cardiovascular events, cardiovascular death, MI, and stroke in patients with chronic coronary artery disease or peripheral artery disease.
This is the sixth indication for rivaroxaban, a factor Xa inhibitor that was first approved in 2011. It is also the first indication for cardiovascular prevention for any factor Xa inhibitor. Others on the U.S. market are apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa).
COMPASS was presented at the 2017 annual congress of the European Society of Cardiology. At that time, Eugene Braunwald, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, commented that the trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease.” He added that the results are “an important step for thrombocardiology.”
when taken with aspirin, Janssen Pharmaceuticals announced on October 11.
The Food and Drug Administration’s approval was based on a review of the 27,000-patient COMPASS trial, which showed last year that a low dosage of rivaroxaban (Xarelto) plus aspirin reduced the combined rate of cardiovascular disease events by 24% in patients with coronary artery disease and by 28% in participants with peripheral artery disease, compared with aspirin alone. (N Engl J Med. 2017 Oct 5;377[14]:1319-30)
The flip side to the reduction in COMPASS’s combined primary endpoint was a 51% increase in major bleeding. However, that bump did not translate to increases in fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) studied two dosages of rivaroxaban, 2.5 mg and 5 mg twice daily, and it was the lower dosage that did the trick. Until this approval, that formulation wasn’t available; Janssen announced the coming of the 2.5-mg pill in its release.
The new prescribing information states specifically that Xarelto 2.5 mg is indicated, in combination with aspirin, to reduce the risk of major cardiovascular events, cardiovascular death, MI, and stroke in patients with chronic coronary artery disease or peripheral artery disease.
This is the sixth indication for rivaroxaban, a factor Xa inhibitor that was first approved in 2011. It is also the first indication for cardiovascular prevention for any factor Xa inhibitor. Others on the U.S. market are apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa).
COMPASS was presented at the 2017 annual congress of the European Society of Cardiology. At that time, Eugene Braunwald, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, commented that the trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease.” He added that the results are “an important step for thrombocardiology.”
CT for evaluating pulmonary embolism overused
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
SAN ANTONIO – The recommended approach to evaluating suspected pulmonary embolism is “greatly underutilized” in the Veterans Health Administration system, Nancy Hsu, MD, said at the annual meeting of the American College of Chest Physicians.
Most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and highly sensitive D-dimer prior to ordering CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), according to results of a survey by Dr. Hsu and her coinvestigator, Guy Soo Hoo, MD.
While CTPA has become the imaging modality of choice for evaluating suspected PE, it is overused and potentially avoidable in one-third of cases, said Dr. Hsu, who is with the VA Greater Los Angeles Healthcare System.
“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”
Dr. Hsu said.
Dr. Hsu and Dr. Soo Hoo surveyed 606 individuals at 18 Veterans Integrated Service Networks (VISNs) and 143 medical centers. A total of 120 fully completed questionnaires were analyzed.
Most respondents (63%) were chiefs, and 80% had 11+ years of experience, Dr. Hsu reported.
Almost all respondents (85%) said CDR with or without D-dimer was not required before ordering a CTPA, survey results show, while only about 7% required both.
“A very small minority of [Veterans Integrated Service Networks], or geographic regions, contained even one hospital that adhered to the guidelines,” Dr. Hsu added.
Though further analysis was limited by sample size, the average CTPA yield for PE appeared to be higher when both components were used in the evaluation, according to Dr. Hsu, who noted an 11.9% yield for CDR plus D-dimer.
Use of CTPA appeared lower at sites with CDR and D-dimer testing, Dr. Hsu added.
These results suggest a need for further research to compare CTPA use and yield in sites that have the algorithm in place, Dr. Hsu told attendees at the meeting.
Adherence to the CDR plus D-dimer diagnostic strategy is “modest at best” despite being a Top 5 Choosing Wisely recommendation in pulmonary medicine, Dr. Hsu told attendees.
The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.
On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, Dr. Hsu said.
“It’s all about balancing risks and benefits,” she said from the podium in a discussion of the study results.
Dr. Hsu and Dr. Soo Hoo disclosed that they had no relationships relevant to their research.
SOURCE: Hsu N et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.937
REPORTING FROM CHEST 2018
Key clinical point: The recommended approach to evaluating suspected pulmonary embolism was underutilized in VA facilities.
Major finding: 85% of respondents said incorporation of a clinical decision rule plus highly sensitive D-dimer was not required prior to CTPA.
Study details: Analysis of 120 survey questionnaires completed by individuals working in Veterans Integrated Service Networks and medical centers.
Disclosures: Study authors reported no conflicts of interest.
Source: Hsu N et al. CHEST 2018 Oct. doi: 10/1016/j.chest.2018.08.937.
Updated ThroLy system predicts need for thromboprophylaxis
DUBROVNIK, CROATIA – An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.
The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients, with a positive predictive value of 22%-25%, a negative predictive value of 96%, sensitivity of 56%-57%, and specificity of 85%-87%.
Darko Antic, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
Dr. Antic said that he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients and the Khorana score is predominantly used for solid tumor malignancies.
The ThroLy scoring system is based on variables used in the Padua and Khorana systems, as well as variables that are specific to lymphoma patients.
In a previous study, the researchers found several variables that were independently associated with risk for VTE in lymphoma, including previous VTE, previous acute MI or stroke, mediastinal involvement, high body mass index, reduced mobility, extranodal localization, neutropenia, and hemoglobin less than 100 g/L (Am J Hematol. 2016 Oct;91[10]:1014-9).
In an initial version of the ThroLy scoring system, previous VTE, previous acute MI/stroke, obesity, and mediastinal involvement were all worth two points, and the other factors were worth a single point in the ThroLy system.
Patients with scores of 0 to 1 were considered low risk, patients with scores of 2 to 3 were considered intermediate risk, and patients with scores of 4 or greater were considered high risk.
To validate and refine ThroLy, Dr. Antic and his colleagues used it to assess 1,723 lymphoma patients treated at eight institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.
Patients had indolent non-Hodgkin lymphoma, aggressive non-Hodgkin lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma. Most subjects (84%) were outpatients. A total of 9%of patients had thrombosis, with 7% having VTE.
ThroLy had a positive predictive value of 17%, compared with 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively. The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua; specificity was 72%, 64%, and 52%, respectively.
“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antic noted.
Updated models
To further improve ThroLy, the researchers updated the system, creating two new models. Model 1 included the type of lymphoma/clinical stage (1 point), previous VTE (5 points), reduced mobility (2 points), hemoglobin less than 100 g/L (1 point), and the presence of vascular devices (1 point). Model 2 included all of the variables in Model 1 plus the thrombophilic condition, which was worth 1 point.
Patients were considered low risk if they scored 2 points or lower and high risk if they scored more than 2 points.
For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%. For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.
There were no major differences in model discrimination and calibration based on the country in which a patient was treated or whether the patient was treated in an inpatient or outpatient setting.
Dr. Antic did not report any conflicts of interest. The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.
The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients, with a positive predictive value of 22%-25%, a negative predictive value of 96%, sensitivity of 56%-57%, and specificity of 85%-87%.
Darko Antic, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
Dr. Antic said that he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients and the Khorana score is predominantly used for solid tumor malignancies.
The ThroLy scoring system is based on variables used in the Padua and Khorana systems, as well as variables that are specific to lymphoma patients.
In a previous study, the researchers found several variables that were independently associated with risk for VTE in lymphoma, including previous VTE, previous acute MI or stroke, mediastinal involvement, high body mass index, reduced mobility, extranodal localization, neutropenia, and hemoglobin less than 100 g/L (Am J Hematol. 2016 Oct;91[10]:1014-9).
In an initial version of the ThroLy scoring system, previous VTE, previous acute MI/stroke, obesity, and mediastinal involvement were all worth two points, and the other factors were worth a single point in the ThroLy system.
Patients with scores of 0 to 1 were considered low risk, patients with scores of 2 to 3 were considered intermediate risk, and patients with scores of 4 or greater were considered high risk.
To validate and refine ThroLy, Dr. Antic and his colleagues used it to assess 1,723 lymphoma patients treated at eight institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.
Patients had indolent non-Hodgkin lymphoma, aggressive non-Hodgkin lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma. Most subjects (84%) were outpatients. A total of 9%of patients had thrombosis, with 7% having VTE.
ThroLy had a positive predictive value of 17%, compared with 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively. The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua; specificity was 72%, 64%, and 52%, respectively.
“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antic noted.
Updated models
To further improve ThroLy, the researchers updated the system, creating two new models. Model 1 included the type of lymphoma/clinical stage (1 point), previous VTE (5 points), reduced mobility (2 points), hemoglobin less than 100 g/L (1 point), and the presence of vascular devices (1 point). Model 2 included all of the variables in Model 1 plus the thrombophilic condition, which was worth 1 point.
Patients were considered low risk if they scored 2 points or lower and high risk if they scored more than 2 points.
For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%. For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.
There were no major differences in model discrimination and calibration based on the country in which a patient was treated or whether the patient was treated in an inpatient or outpatient setting.
Dr. Antic did not report any conflicts of interest. The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.
The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients, with a positive predictive value of 22%-25%, a negative predictive value of 96%, sensitivity of 56%-57%, and specificity of 85%-87%.
Darko Antic, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
Dr. Antic said that he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients and the Khorana score is predominantly used for solid tumor malignancies.
The ThroLy scoring system is based on variables used in the Padua and Khorana systems, as well as variables that are specific to lymphoma patients.
In a previous study, the researchers found several variables that were independently associated with risk for VTE in lymphoma, including previous VTE, previous acute MI or stroke, mediastinal involvement, high body mass index, reduced mobility, extranodal localization, neutropenia, and hemoglobin less than 100 g/L (Am J Hematol. 2016 Oct;91[10]:1014-9).
In an initial version of the ThroLy scoring system, previous VTE, previous acute MI/stroke, obesity, and mediastinal involvement were all worth two points, and the other factors were worth a single point in the ThroLy system.
Patients with scores of 0 to 1 were considered low risk, patients with scores of 2 to 3 were considered intermediate risk, and patients with scores of 4 or greater were considered high risk.
To validate and refine ThroLy, Dr. Antic and his colleagues used it to assess 1,723 lymphoma patients treated at eight institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.
Patients had indolent non-Hodgkin lymphoma, aggressive non-Hodgkin lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma. Most subjects (84%) were outpatients. A total of 9%of patients had thrombosis, with 7% having VTE.
ThroLy had a positive predictive value of 17%, compared with 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively. The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua; specificity was 72%, 64%, and 52%, respectively.
“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antic noted.
Updated models
To further improve ThroLy, the researchers updated the system, creating two new models. Model 1 included the type of lymphoma/clinical stage (1 point), previous VTE (5 points), reduced mobility (2 points), hemoglobin less than 100 g/L (1 point), and the presence of vascular devices (1 point). Model 2 included all of the variables in Model 1 plus the thrombophilic condition, which was worth 1 point.
Patients were considered low risk if they scored 2 points or lower and high risk if they scored more than 2 points.
For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%. For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.
There were no major differences in model discrimination and calibration based on the country in which a patient was treated or whether the patient was treated in an inpatient or outpatient setting.
Dr. Antic did not report any conflicts of interest. The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Association, which is owned by the parent company of this news organization.
REPORTING FROM LEUKEMIA AND LYMPHOMA 2018
Key clinical point:
Major finding: The updated ThroLy had a positive predictive value of 22%-25%, a negative predictive value of 96%, sensitivity of 56%-57%, and specificity of 85%-87%.
Study details: The scoring system was validated on 1,723 lymphoma patients treated at eight institutions worldwide.
Disclosures: Dr. Antic reported having no conflicts of interest.
Genomic profiling predicts outcomes in patients with MPN
Genomic characteristics of patients with myeloproliferative neoplasms (MPN) can predict clinical outcomes, a recent study found.
Eight genomic subgroups of MPN were recognized, each with distinct clinical features, including event-free survival, risk of leukemic transformation, and blood counts, according to Jacob Grinfeld, MD, of the Wellcome-MRC Cambridge (England) Stem Cell Institute and Cambridge Institute for Medical Research and his colleagues.
“Current classification schemes distinguish among the subtypes of myeloproliferative neoplasms according to clinical and laboratory features, but uncertainty clouds where and how to draw dividing lines among them,” the investigators wrote in the New England Journal of Medicine. “In blood cancers, a progressive shift is under way, from clinical and morphologic classification schemes to those that are based on genomics.”
MPNs are often driven by mutations in CALR, MPL, or JAK2 genes, but classification is not confined to just three genomic types; many patients have additional driver mutations throughout a variety of cancer genes, and it is these additional mutations that are responsible for the wide range of disease phenotypes and clinical outcomes.
This study included 2,035 patients with MPNs, including essential thrombocythemia, polycythemia vera, myelofibrosis, and other MPN diagnoses. The investigators performed targeted sequencing for the full coding sequence of 69 genes and genomewide copy-number information in 1,887 patients. Another 148 patients underwent whole-exome sequencing.
By sequencing coding exons from 69 myeloid cancer genes, the investigators were able to survey the diversity of mutations across a population of patients with MPNs and identify mutation-associated clinical outcomes.
The results showed that slightly less than half (45%) of the patients had a solitary abnormality in CALR, MPL, or JAK2, while the remaining patients had additional driver mutations. In some instances, additional mutations were numerous, particularly in older patients with advanced disease. In at least five cases, 33 genes had driver mutations.
Further analysis identified eight genomic subgroups that could predict clinical outcomes based on shared chromosomal abnormalities and mutations. For example, one subgroup included patients with TP53 mutations; these individuals had a “dismal prognosis” and were 15.5 times more likely to transform to acute myeloid leukemia (AML), compared with the JAK2-heterozygous subgroup (P less than .001).
Because prognosis is “a key determinant of the treatment of patients with MPNs,” genomic subgrouping may one day guide clinical decision making, the investigators concluded.
To further this cause, the investigators have made available an online calculator of individualized patient outcomes, which can be accessed at https://cancer.sanger.ac.uk/mpn-multistage/.
The study was funded by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, and others. Some study authors reported fees from Celgene, Novartis, Gilead, Shire, and others outside of the study.
SOURCE: Grinfeld J et al. N Engl J Med. 2018;379:1416-30.
Genomic characteristics of patients with myeloproliferative neoplasms (MPN) can predict clinical outcomes, a recent study found.
Eight genomic subgroups of MPN were recognized, each with distinct clinical features, including event-free survival, risk of leukemic transformation, and blood counts, according to Jacob Grinfeld, MD, of the Wellcome-MRC Cambridge (England) Stem Cell Institute and Cambridge Institute for Medical Research and his colleagues.
“Current classification schemes distinguish among the subtypes of myeloproliferative neoplasms according to clinical and laboratory features, but uncertainty clouds where and how to draw dividing lines among them,” the investigators wrote in the New England Journal of Medicine. “In blood cancers, a progressive shift is under way, from clinical and morphologic classification schemes to those that are based on genomics.”
MPNs are often driven by mutations in CALR, MPL, or JAK2 genes, but classification is not confined to just three genomic types; many patients have additional driver mutations throughout a variety of cancer genes, and it is these additional mutations that are responsible for the wide range of disease phenotypes and clinical outcomes.
This study included 2,035 patients with MPNs, including essential thrombocythemia, polycythemia vera, myelofibrosis, and other MPN diagnoses. The investigators performed targeted sequencing for the full coding sequence of 69 genes and genomewide copy-number information in 1,887 patients. Another 148 patients underwent whole-exome sequencing.
By sequencing coding exons from 69 myeloid cancer genes, the investigators were able to survey the diversity of mutations across a population of patients with MPNs and identify mutation-associated clinical outcomes.
The results showed that slightly less than half (45%) of the patients had a solitary abnormality in CALR, MPL, or JAK2, while the remaining patients had additional driver mutations. In some instances, additional mutations were numerous, particularly in older patients with advanced disease. In at least five cases, 33 genes had driver mutations.
Further analysis identified eight genomic subgroups that could predict clinical outcomes based on shared chromosomal abnormalities and mutations. For example, one subgroup included patients with TP53 mutations; these individuals had a “dismal prognosis” and were 15.5 times more likely to transform to acute myeloid leukemia (AML), compared with the JAK2-heterozygous subgroup (P less than .001).
Because prognosis is “a key determinant of the treatment of patients with MPNs,” genomic subgrouping may one day guide clinical decision making, the investigators concluded.
To further this cause, the investigators have made available an online calculator of individualized patient outcomes, which can be accessed at https://cancer.sanger.ac.uk/mpn-multistage/.
The study was funded by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, and others. Some study authors reported fees from Celgene, Novartis, Gilead, Shire, and others outside of the study.
SOURCE: Grinfeld J et al. N Engl J Med. 2018;379:1416-30.
Genomic characteristics of patients with myeloproliferative neoplasms (MPN) can predict clinical outcomes, a recent study found.
Eight genomic subgroups of MPN were recognized, each with distinct clinical features, including event-free survival, risk of leukemic transformation, and blood counts, according to Jacob Grinfeld, MD, of the Wellcome-MRC Cambridge (England) Stem Cell Institute and Cambridge Institute for Medical Research and his colleagues.
“Current classification schemes distinguish among the subtypes of myeloproliferative neoplasms according to clinical and laboratory features, but uncertainty clouds where and how to draw dividing lines among them,” the investigators wrote in the New England Journal of Medicine. “In blood cancers, a progressive shift is under way, from clinical and morphologic classification schemes to those that are based on genomics.”
MPNs are often driven by mutations in CALR, MPL, or JAK2 genes, but classification is not confined to just three genomic types; many patients have additional driver mutations throughout a variety of cancer genes, and it is these additional mutations that are responsible for the wide range of disease phenotypes and clinical outcomes.
This study included 2,035 patients with MPNs, including essential thrombocythemia, polycythemia vera, myelofibrosis, and other MPN diagnoses. The investigators performed targeted sequencing for the full coding sequence of 69 genes and genomewide copy-number information in 1,887 patients. Another 148 patients underwent whole-exome sequencing.
By sequencing coding exons from 69 myeloid cancer genes, the investigators were able to survey the diversity of mutations across a population of patients with MPNs and identify mutation-associated clinical outcomes.
The results showed that slightly less than half (45%) of the patients had a solitary abnormality in CALR, MPL, or JAK2, while the remaining patients had additional driver mutations. In some instances, additional mutations were numerous, particularly in older patients with advanced disease. In at least five cases, 33 genes had driver mutations.
Further analysis identified eight genomic subgroups that could predict clinical outcomes based on shared chromosomal abnormalities and mutations. For example, one subgroup included patients with TP53 mutations; these individuals had a “dismal prognosis” and were 15.5 times more likely to transform to acute myeloid leukemia (AML), compared with the JAK2-heterozygous subgroup (P less than .001).
Because prognosis is “a key determinant of the treatment of patients with MPNs,” genomic subgrouping may one day guide clinical decision making, the investigators concluded.
To further this cause, the investigators have made available an online calculator of individualized patient outcomes, which can be accessed at https://cancer.sanger.ac.uk/mpn-multistage/.
The study was funded by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, and others. Some study authors reported fees from Celgene, Novartis, Gilead, Shire, and others outside of the study.
SOURCE: Grinfeld J et al. N Engl J Med. 2018;379:1416-30.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Eight genomic subgroups of MPN were recognized, each with distinct clinical features, including event-free survival, risk of leukemic transformation, and blood counts.
Study details: A gene sequencing study involving 2,035 patients with MPN.
Disclosures: The study was funded by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, and others. Some study authors reported fees from Celgene, Novartis, Gilead, Shire, and others outside of the study.
Source: Grinfeld J et al. N Engl J Med. 2018;379:1416-30.
GARFIELD-AF registry: DOACs cut mortality 19%
MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.
Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.
The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.
These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.
First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.
“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”
The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.
GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.
GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.
MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.
Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.
The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.
These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.
First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.
“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”
The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.
GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.
GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.
MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.
Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.
The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.
These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.
First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.
“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”
The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.
GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.
GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point:
Major finding: Direct oral anticoagulant–treated patients had a 19% relative reduction in all-cause death, compared with patients on a vitamin K antagonist.
Study details: The GARFIELD-AF registry, which included 26,742 patients with newly diagnosed atrial fibrillation.
Disclosures: GARFIELD-AF was funded in part by Bayer. Dr. Camm has been an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.
Obesity paradox extends to PE patients
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
REPORTING FROM CHEST 2018
Key clinical point: The obesity paradox observed in other chronic conditions held true in this study of patients with pulmonary embolism (PE).
Major finding: Obese PE patients had more risk factors and more severe disease, but an overall mortality of 2.2% vs 3.7% in nonobese PE patients.
Study details: Retrospective analysis of the National Inpatient Sample (NIS) database including almost 2 million individuals with a primary discharge diagnosis of PE.
Disclosures: Study authors had no disclosures.
Source: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
Variant not associated with CLL, AIHA, or ITP in certain patients
DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL1 and autoimmune diseases2 in patients from Northwest Europe.
However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.
| CLL | AIHA | ITP | Controls | |
| Minor T allele | 0.107 | 0.067 | 0.036 | 0.05 |
| CC genotype | 0.809 | 0.166 | 0.023 | 0.901 |
| CT genotype | 0.9 | 0.067 | 0.033 | 0.099 |
| TT genotype | 0.928 | 0.072 | 0 | 0 |
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221
2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032
DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL1 and autoimmune diseases2 in patients from Northwest Europe.
However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.
| CLL | AIHA | ITP | Controls | |
| Minor T allele | 0.107 | 0.067 | 0.036 | 0.05 |
| CC genotype | 0.809 | 0.166 | 0.023 | 0.901 |
| CT genotype | 0.9 | 0.067 | 0.033 | 0.099 |
| TT genotype | 0.928 | 0.072 | 0 | 0 |
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221
2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032
DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.
Past studies have shown an association between the PTPN22 R620W variant and both CLL1 and autoimmune diseases2 in patients from Northwest Europe.
However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.
Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.
Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.
The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.
The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.
| CLL | AIHA | ITP | Controls | |
| Minor T allele | 0.107 | 0.067 | 0.036 | 0.05 |
| CC genotype | 0.809 | 0.166 | 0.023 | 0.901 |
| CT genotype | 0.9 | 0.067 | 0.033 | 0.099 |
| TT genotype | 0.928 | 0.072 | 0 | 0 |
Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.
She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.
Dr. Panovska-Stavridis did not declare any conflicts of interest.
1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221
2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032