Venous Thromboembolism

SAN DIEGO – In critically ill patients receiving pharmacologic thromboprophylaxis, adjunct intermittent pneumatic compression (IPC) had no effect on the rates of lower-limb deep vein thrombosis (DVT), according to a new trial.

Jim Kling/MDedge News

“I was surprised. My hypothesis was that it would work,” said lead author Yaseen M. Arabi, MD, chairman of the intensive care department at King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Many physicians routinely carry out the practice on the assumption that IPC should lead to better blood flow and further cut DVT risk. The procedure carries few risks, aside from patient discomfort. “The main issue is that it’s not needed. It might be useful in patients who are not receiving heparin or low-molecular-weight heparin,” said Dr. Arabi, who presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. The study was simultaneously published online in the New England Journal of Medicine.

Unfractionated or low-molecular-weight heparin reduces the risk of DVT by about 50%, but about 5%-20% of critically ill patients will develop DVT in spite of treatment, and mechanical thromboprophylaxis reduces DVT risk, compared with no prophylaxis. Some researchers have attempted to address whether adjunct intermittent pneumatic compression could further reduce DVT risk, but their studies were marked by a lack of controls, unoptimized pharmacologic regimens, and other limitations.

The trial included 2,003 adults from 20 sites in Saudi Arabia, Canada, Australia, and India, who were expected to have an intensive care unit stay of at least 72 hours. They were randomized to receive IPC combined with pharmacologic thromboprophylaxis (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control).

SOURCE: Arabi Y et al. CCC48, Abstract 142. N Engl J Med Feb 18. doi: 10.1056/NEJMoa1816150.

SAN DIEGO – In critically ill patients receiving pharmacologic thromboprophylaxis, adjunct intermittent pneumatic compression (IPC) had no effect on the rates of lower-limb deep vein thrombosis (DVT), according to a new trial.

Jim Kling/MDedge News

“I was surprised. My hypothesis was that it would work,” said lead author Yaseen M. Arabi, MD, chairman of the intensive care department at King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Many physicians routinely carry out the practice on the assumption that IPC should lead to better blood flow and further cut DVT risk. The procedure carries few risks, aside from patient discomfort. “The main issue is that it’s not needed. It might be useful in patients who are not receiving heparin or low-molecular-weight heparin,” said Dr. Arabi, who presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. The study was simultaneously published online in the New England Journal of Medicine.

Unfractionated or low-molecular-weight heparin reduces the risk of DVT by about 50%, but about 5%-20% of critically ill patients will develop DVT in spite of treatment, and mechanical thromboprophylaxis reduces DVT risk, compared with no prophylaxis. Some researchers have attempted to address whether adjunct intermittent pneumatic compression could further reduce DVT risk, but their studies were marked by a lack of controls, unoptimized pharmacologic regimens, and other limitations.

The trial included 2,003 adults from 20 sites in Saudi Arabia, Canada, Australia, and India, who were expected to have an intensive care unit stay of at least 72 hours. They were randomized to receive IPC combined with pharmacologic thromboprophylaxis (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control).

SOURCE: Arabi Y et al. CCC48, Abstract 142. N Engl J Med Feb 18. doi: 10.1056/NEJMoa1816150.

SAN DIEGO – In critically ill patients receiving pharmacologic thromboprophylaxis, adjunct intermittent pneumatic compression (IPC) had no effect on the rates of lower-limb deep vein thrombosis (DVT), according to a new trial.

Jim Kling/MDedge News

“I was surprised. My hypothesis was that it would work,” said lead author Yaseen M. Arabi, MD, chairman of the intensive care department at King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Many physicians routinely carry out the practice on the assumption that IPC should lead to better blood flow and further cut DVT risk. The procedure carries few risks, aside from patient discomfort. “The main issue is that it’s not needed. It might be useful in patients who are not receiving heparin or low-molecular-weight heparin,” said Dr. Arabi, who presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. The study was simultaneously published online in the New England Journal of Medicine.

Unfractionated or low-molecular-weight heparin reduces the risk of DVT by about 50%, but about 5%-20% of critically ill patients will develop DVT in spite of treatment, and mechanical thromboprophylaxis reduces DVT risk, compared with no prophylaxis. Some researchers have attempted to address whether adjunct intermittent pneumatic compression could further reduce DVT risk, but their studies were marked by a lack of controls, unoptimized pharmacologic regimens, and other limitations.

The trial included 2,003 adults from 20 sites in Saudi Arabia, Canada, Australia, and India, who were expected to have an intensive care unit stay of at least 72 hours. They were randomized to receive IPC combined with pharmacologic thromboprophylaxis (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control).

SOURCE: Arabi Y et al. CCC48, Abstract 142. N Engl J Med Feb 18. doi: 10.1056/NEJMoa1816150.

Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).

We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).

We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

Patients with acute major bleeding associated with factor Xa inhibitor usage who received andexanet alfa experienced a significant decrease in anti–factor Xa activity, with more than three-quarters of patients experiencing good or excellent hemostatic efficiency after 12 hours. That finding emerged from the multicenter, prospective, open-label, single-group ANNEXA-4 trial published in the New England Journal of Medicine (2019 Feb 11. doi: 10.1056/NEJMoa1814051).

We reported this story at the annual meeting of the American College of Cardiology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.

SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

WASHINGTON – Unquestionably, immunotherapy is revolutionizing the care of patients with various solid tumors and hematologic malignancies.

Neil Osterweil/MDedge News

But it’s equally true that there’s no such thing as either a free lunch or a cancer therapy free of side effects, whether it’s increased risk for heart failure associated with anthracycline-based chemotherapy, or inflammatory conditions, arrhythmias, and thromboembolic events associated with immune checkpoint inhibitors, said R. Frank Cornell, MD, of Vanderbilt University Medical Center in Nashville, Tenn.

“Early awareness and intervention is critical for improved outcomes, and a multidisciplinary approach between oncology, cardiology, the clinic nurse, and other health care providers is critical in managing these patients with these complicated therapies,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Checkpoint inhibitors and the heart

Toxicities associated with immune checkpoint inhibitors such as the programmed death 1/ligand 1 (PD-1/PD-L1) inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) and the cytotoxic T-lymphocyte antigen 4 antibody ipilimumab (Yervoy) tend to mimic autoimmune conditions, Dr. Cornell said.

Cardiovascular events associated with these agents, while uncommon, include myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, vasculitis, and venous thromboembolism, he said, citing an American Society of Clinical Oncology (ASCO) clinical practice guideline (J Clin Oncol 2018;36[17]:1714-68).

Dr. Cornell described the case of a 63-year-old woman with disseminated metastatic melanoma who presented to the emergency department 10 days after starting on combination therapy with ipilimumab and nivolumab. She had developed shortness of breath, pleuritic chest pain, and a mild cough for 1 or 2 days.

Her cardiac laboratory markers had been normal at baseline, but were markedly elevated on presentation, and electrocardiograms showed complete heart block and subsequent ventricular tachycardia.

The patient was started on high-dose prednisone, but she died in hospital, and an autopsy showed that the cause of death was infiltration into the myocardium of CD3-positive and CD8-positive T lymphocytes.

“So how do we manage this? This is a good opportunity, I think, for further cardiology and oncology collaboration to develop more robust guidelines for what we can do to best prevent this,” Dr. Cornell said.

Patients started on the ipilimumab/nivolumab combination should be tested weekly for cardiac troponin, creatine kinase (CK) and CK-muscle/brain (CK-MB) weekly for the first 3-4 weeks of therapy. Therapy should be stopped if troponin levels continue to rise, and the patient should be started on high-dose steroids, he said.

The role of other anti-inflammatory agents such as infliximab (Remicade and biosimilars) is unclear and needs further study, he added.

Dr. Cornell cited a 2018 letter to The Lancet by Javid J. Moslehi, MD, and colleagues from Vanderbilt describing an increase in reports of fatal myocarditis among patients treated with checkpoint inhibitors.

“We highlight the high mortality rate with severe immune checkpoint inhibitor–related myocarditis, which is more frequent with combination PD-1 and CTLA-4 blockade, but can also occur with monotherapy. Myocarditis was observed across immune checkpoint inhibitor regimens, although it remains too early to determine whether the incidence differs between use of anti-PD1 and anti-PD-L1 drugs. Furthermore, this condition occurs early on during therapy and across cancer types,” they wrote.

Most of the patients had no preexisting cardiovascular disease, and most were not taking medications for hypertension, cardiovascular disease, or diabetes.
 

CAR-T cells and cardiac disease

The primary cardiac complications associated with CAR-T cell therapy are related to the cytokine release syndrome (CRS), a condition marked by progressive elevation in inflammatory cytokines that in turn leads to marked elevations in C-reactive protein (CRP), interferon gamma, tumor necrosis factor al, and release of pro-inflammatory cytokines including interleukin (IL) 6, IL-10, IL-12, and IL-1 beta.

In rare instances, CRS can lead to disseminated intravascular coagulation (DIC), capillary leak syndrome, and a hemophagocytic lymphohistiocytosis-like (HLH) syndrome, Dr. Cornell said.

Package inserts for the two Food and Drug Administration–approved CAR-T cell products, axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) show that each was associated in clinical trials with a high incidence of CRS.

Among patients treated with axicabtagene ciloleucel, 94% developed CRS, which was grade 3 or greater in severity in 13%. The median time to onset was 2 days, and the median duration was 7 days. Cardiovascular adverse events included grade 3 or greater tachycardia in 2%, arrhythmias in 7%, edema in 1%, dyspnea in 3%, pleural effusion in 2%, hypotension in 15%, hypertension in 6%, and thrombosis in 1%.

Among patients treated with tisagenlecleucel, 79% treated for B-cell acute lymphoblastic leukemia (B-ALL) and 74% treated for diffuse large B cell lymphoma (DLBCL) developed CRS, which was grade 3 or greater in 49% and 23% of patients, respectively. The median time to onset was 3 days, and the median duration of CRS was 8 days.

Cardiovascular adverse events of grade 3 or greater among these patients included tachycardia in 4%, fluid overload in 7%, edema in 1%, dyspnea in 12%, pulmonary edema in 4%, hypotension in 22%, and hypertension in 6%.

Risk factors for CRS include high pre-infusion tumor burden, active infections, and concurrent inflammatory processes, Dr. Cornell said.

Prevention of cardiovascular complications of CAR-T cell therapy requires management of CRS. Patients with grade 2 or greater CRS should receive the anti-IL-6 agent tocilizumab (Actemra) 8 mg/kg intravenously over 1 hour to a maximum dose of 800 mg. Tocilizumab infusions can be repeated every 8 hours as needed if the patient is not responsive to intravenous fluids or increasing supplement oxygen, but should be limited to a maximum of three doses over 24 hours, and a maximum total of four doses.

Patients with grade 3 CRS should also receive intravenous methylprednisolone 1 mg/kg twice daily or the equivalent amount of dexamethasone, with corticosteroids continued until the severity of CRS is grade 1 or less, then tapered over 3 days,

Patients with grade 4 CRS should also receive IV methylprednisolone 1,000 mg per day for 3 days, and if symptoms improve, continue management as per grade 3, Dr. Cornell said.

Dr. Cornell reported having nothing to disclose.

WASHINGTON – Unquestionably, immunotherapy is revolutionizing the care of patients with various solid tumors and hematologic malignancies.

Neil Osterweil/MDedge News

But it’s equally true that there’s no such thing as either a free lunch or a cancer therapy free of side effects, whether it’s increased risk for heart failure associated with anthracycline-based chemotherapy, or inflammatory conditions, arrhythmias, and thromboembolic events associated with immune checkpoint inhibitors, said R. Frank Cornell, MD, of Vanderbilt University Medical Center in Nashville, Tenn.

“Early awareness and intervention is critical for improved outcomes, and a multidisciplinary approach between oncology, cardiology, the clinic nurse, and other health care providers is critical in managing these patients with these complicated therapies,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Checkpoint inhibitors and the heart

Toxicities associated with immune checkpoint inhibitors such as the programmed death 1/ligand 1 (PD-1/PD-L1) inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) and the cytotoxic T-lymphocyte antigen 4 antibody ipilimumab (Yervoy) tend to mimic autoimmune conditions, Dr. Cornell said.

Cardiovascular events associated with these agents, while uncommon, include myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, vasculitis, and venous thromboembolism, he said, citing an American Society of Clinical Oncology (ASCO) clinical practice guideline (J Clin Oncol 2018;36[17]:1714-68).

Dr. Cornell described the case of a 63-year-old woman with disseminated metastatic melanoma who presented to the emergency department 10 days after starting on combination therapy with ipilimumab and nivolumab. She had developed shortness of breath, pleuritic chest pain, and a mild cough for 1 or 2 days.

Her cardiac laboratory markers had been normal at baseline, but were markedly elevated on presentation, and electrocardiograms showed complete heart block and subsequent ventricular tachycardia.

The patient was started on high-dose prednisone, but she died in hospital, and an autopsy showed that the cause of death was infiltration into the myocardium of CD3-positive and CD8-positive T lymphocytes.

“So how do we manage this? This is a good opportunity, I think, for further cardiology and oncology collaboration to develop more robust guidelines for what we can do to best prevent this,” Dr. Cornell said.

Patients started on the ipilimumab/nivolumab combination should be tested weekly for cardiac troponin, creatine kinase (CK) and CK-muscle/brain (CK-MB) weekly for the first 3-4 weeks of therapy. Therapy should be stopped if troponin levels continue to rise, and the patient should be started on high-dose steroids, he said.

The role of other anti-inflammatory agents such as infliximab (Remicade and biosimilars) is unclear and needs further study, he added.

Dr. Cornell cited a 2018 letter to The Lancet by Javid J. Moslehi, MD, and colleagues from Vanderbilt describing an increase in reports of fatal myocarditis among patients treated with checkpoint inhibitors.

“We highlight the high mortality rate with severe immune checkpoint inhibitor–related myocarditis, which is more frequent with combination PD-1 and CTLA-4 blockade, but can also occur with monotherapy. Myocarditis was observed across immune checkpoint inhibitor regimens, although it remains too early to determine whether the incidence differs between use of anti-PD1 and anti-PD-L1 drugs. Furthermore, this condition occurs early on during therapy and across cancer types,” they wrote.

Most of the patients had no preexisting cardiovascular disease, and most were not taking medications for hypertension, cardiovascular disease, or diabetes.
 

CAR-T cells and cardiac disease

The primary cardiac complications associated with CAR-T cell therapy are related to the cytokine release syndrome (CRS), a condition marked by progressive elevation in inflammatory cytokines that in turn leads to marked elevations in C-reactive protein (CRP), interferon gamma, tumor necrosis factor al, and release of pro-inflammatory cytokines including interleukin (IL) 6, IL-10, IL-12, and IL-1 beta.

In rare instances, CRS can lead to disseminated intravascular coagulation (DIC), capillary leak syndrome, and a hemophagocytic lymphohistiocytosis-like (HLH) syndrome, Dr. Cornell said.

Package inserts for the two Food and Drug Administration–approved CAR-T cell products, axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) show that each was associated in clinical trials with a high incidence of CRS.

Among patients treated with axicabtagene ciloleucel, 94% developed CRS, which was grade 3 or greater in severity in 13%. The median time to onset was 2 days, and the median duration was 7 days. Cardiovascular adverse events included grade 3 or greater tachycardia in 2%, arrhythmias in 7%, edema in 1%, dyspnea in 3%, pleural effusion in 2%, hypotension in 15%, hypertension in 6%, and thrombosis in 1%.

Among patients treated with tisagenlecleucel, 79% treated for B-cell acute lymphoblastic leukemia (B-ALL) and 74% treated for diffuse large B cell lymphoma (DLBCL) developed CRS, which was grade 3 or greater in 49% and 23% of patients, respectively. The median time to onset was 3 days, and the median duration of CRS was 8 days.

Cardiovascular adverse events of grade 3 or greater among these patients included tachycardia in 4%, fluid overload in 7%, edema in 1%, dyspnea in 12%, pulmonary edema in 4%, hypotension in 22%, and hypertension in 6%.

Risk factors for CRS include high pre-infusion tumor burden, active infections, and concurrent inflammatory processes, Dr. Cornell said.

Prevention of cardiovascular complications of CAR-T cell therapy requires management of CRS. Patients with grade 2 or greater CRS should receive the anti-IL-6 agent tocilizumab (Actemra) 8 mg/kg intravenously over 1 hour to a maximum dose of 800 mg. Tocilizumab infusions can be repeated every 8 hours as needed if the patient is not responsive to intravenous fluids or increasing supplement oxygen, but should be limited to a maximum of three doses over 24 hours, and a maximum total of four doses.

Patients with grade 3 CRS should also receive intravenous methylprednisolone 1 mg/kg twice daily or the equivalent amount of dexamethasone, with corticosteroids continued until the severity of CRS is grade 1 or less, then tapered over 3 days,

Patients with grade 4 CRS should also receive IV methylprednisolone 1,000 mg per day for 3 days, and if symptoms improve, continue management as per grade 3, Dr. Cornell said.

Dr. Cornell reported having nothing to disclose.

WASHINGTON – Unquestionably, immunotherapy is revolutionizing the care of patients with various solid tumors and hematologic malignancies.

Neil Osterweil/MDedge News

But it’s equally true that there’s no such thing as either a free lunch or a cancer therapy free of side effects, whether it’s increased risk for heart failure associated with anthracycline-based chemotherapy, or inflammatory conditions, arrhythmias, and thromboembolic events associated with immune checkpoint inhibitors, said R. Frank Cornell, MD, of Vanderbilt University Medical Center in Nashville, Tenn.

“Early awareness and intervention is critical for improved outcomes, and a multidisciplinary approach between oncology, cardiology, the clinic nurse, and other health care providers is critical in managing these patients with these complicated therapies,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Checkpoint inhibitors and the heart

Toxicities associated with immune checkpoint inhibitors such as the programmed death 1/ligand 1 (PD-1/PD-L1) inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) and the cytotoxic T-lymphocyte antigen 4 antibody ipilimumab (Yervoy) tend to mimic autoimmune conditions, Dr. Cornell said.

Cardiovascular events associated with these agents, while uncommon, include myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, vasculitis, and venous thromboembolism, he said, citing an American Society of Clinical Oncology (ASCO) clinical practice guideline (J Clin Oncol 2018;36[17]:1714-68).

Dr. Cornell described the case of a 63-year-old woman with disseminated metastatic melanoma who presented to the emergency department 10 days after starting on combination therapy with ipilimumab and nivolumab. She had developed shortness of breath, pleuritic chest pain, and a mild cough for 1 or 2 days.

Her cardiac laboratory markers had been normal at baseline, but were markedly elevated on presentation, and electrocardiograms showed complete heart block and subsequent ventricular tachycardia.

The patient was started on high-dose prednisone, but she died in hospital, and an autopsy showed that the cause of death was infiltration into the myocardium of CD3-positive and CD8-positive T lymphocytes.

“So how do we manage this? This is a good opportunity, I think, for further cardiology and oncology collaboration to develop more robust guidelines for what we can do to best prevent this,” Dr. Cornell said.

Patients started on the ipilimumab/nivolumab combination should be tested weekly for cardiac troponin, creatine kinase (CK) and CK-muscle/brain (CK-MB) weekly for the first 3-4 weeks of therapy. Therapy should be stopped if troponin levels continue to rise, and the patient should be started on high-dose steroids, he said.

The role of other anti-inflammatory agents such as infliximab (Remicade and biosimilars) is unclear and needs further study, he added.

Dr. Cornell cited a 2018 letter to The Lancet by Javid J. Moslehi, MD, and colleagues from Vanderbilt describing an increase in reports of fatal myocarditis among patients treated with checkpoint inhibitors.

“We highlight the high mortality rate with severe immune checkpoint inhibitor–related myocarditis, which is more frequent with combination PD-1 and CTLA-4 blockade, but can also occur with monotherapy. Myocarditis was observed across immune checkpoint inhibitor regimens, although it remains too early to determine whether the incidence differs between use of anti-PD1 and anti-PD-L1 drugs. Furthermore, this condition occurs early on during therapy and across cancer types,” they wrote.

Most of the patients had no preexisting cardiovascular disease, and most were not taking medications for hypertension, cardiovascular disease, or diabetes.
 

CAR-T cells and cardiac disease

The primary cardiac complications associated with CAR-T cell therapy are related to the cytokine release syndrome (CRS), a condition marked by progressive elevation in inflammatory cytokines that in turn leads to marked elevations in C-reactive protein (CRP), interferon gamma, tumor necrosis factor al, and release of pro-inflammatory cytokines including interleukin (IL) 6, IL-10, IL-12, and IL-1 beta.

In rare instances, CRS can lead to disseminated intravascular coagulation (DIC), capillary leak syndrome, and a hemophagocytic lymphohistiocytosis-like (HLH) syndrome, Dr. Cornell said.

Package inserts for the two Food and Drug Administration–approved CAR-T cell products, axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) show that each was associated in clinical trials with a high incidence of CRS.

Among patients treated with axicabtagene ciloleucel, 94% developed CRS, which was grade 3 or greater in severity in 13%. The median time to onset was 2 days, and the median duration was 7 days. Cardiovascular adverse events included grade 3 or greater tachycardia in 2%, arrhythmias in 7%, edema in 1%, dyspnea in 3%, pleural effusion in 2%, hypotension in 15%, hypertension in 6%, and thrombosis in 1%.

Among patients treated with tisagenlecleucel, 79% treated for B-cell acute lymphoblastic leukemia (B-ALL) and 74% treated for diffuse large B cell lymphoma (DLBCL) developed CRS, which was grade 3 or greater in 49% and 23% of patients, respectively. The median time to onset was 3 days, and the median duration of CRS was 8 days.

Cardiovascular adverse events of grade 3 or greater among these patients included tachycardia in 4%, fluid overload in 7%, edema in 1%, dyspnea in 12%, pulmonary edema in 4%, hypotension in 22%, and hypertension in 6%.

Risk factors for CRS include high pre-infusion tumor burden, active infections, and concurrent inflammatory processes, Dr. Cornell said.

Prevention of cardiovascular complications of CAR-T cell therapy requires management of CRS. Patients with grade 2 or greater CRS should receive the anti-IL-6 agent tocilizumab (Actemra) 8 mg/kg intravenously over 1 hour to a maximum dose of 800 mg. Tocilizumab infusions can be repeated every 8 hours as needed if the patient is not responsive to intravenous fluids or increasing supplement oxygen, but should be limited to a maximum of three doses over 24 hours, and a maximum total of four doses.

Patients with grade 3 CRS should also receive intravenous methylprednisolone 1 mg/kg twice daily or the equivalent amount of dexamethasone, with corticosteroids continued until the severity of CRS is grade 1 or less, then tapered over 3 days,

Patients with grade 4 CRS should also receive IV methylprednisolone 1,000 mg per day for 3 days, and if symptoms improve, continue management as per grade 3, Dr. Cornell said.

Dr. Cornell reported having nothing to disclose.

Terrific Care and Medex are recalling CoaguChek XS PT test strips they distributed between Dec. 27, 2017, and Dec. 15, 2018. According to a release, the Food and Drug Administration has identified this recall as Class I, which is the most serious type of recall and indicates that “use of these devices may cause serious injuries or death.”

These strips are used by patients taking warfarin to help determine the patients’ international normalized ratio, which doctors and patients then use to decide whether the dose is appropriate. Roche Diagnostics, the strips’ manufacturer, issued a recall in September 2018; the test strips distributed by Terrific Care and Medex, however, were not labeled or authorized for sale in the United States and were therefore not included in that original recall. According to the release, the strips in this recall, which was initiated Dec. 21, 2018, were purchased by Terrific Care and Medex from an unknown source and then distributed in the United States. On Jan. 28, 2019, Terrific Care sent an Urgent Medical Device Recall Notification Letter to customers.

The full recall is described on the FDA website.
 

cpalmer@mdedge.com

Terrific Care and Medex are recalling CoaguChek XS PT test strips they distributed between Dec. 27, 2017, and Dec. 15, 2018. According to a release, the Food and Drug Administration has identified this recall as Class I, which is the most serious type of recall and indicates that “use of these devices may cause serious injuries or death.”

These strips are used by patients taking warfarin to help determine the patients’ international normalized ratio, which doctors and patients then use to decide whether the dose is appropriate. Roche Diagnostics, the strips’ manufacturer, issued a recall in September 2018; the test strips distributed by Terrific Care and Medex, however, were not labeled or authorized for sale in the United States and were therefore not included in that original recall. According to the release, the strips in this recall, which was initiated Dec. 21, 2018, were purchased by Terrific Care and Medex from an unknown source and then distributed in the United States. On Jan. 28, 2019, Terrific Care sent an Urgent Medical Device Recall Notification Letter to customers.

The full recall is described on the FDA website.
 

cpalmer@mdedge.com

Terrific Care and Medex are recalling CoaguChek XS PT test strips they distributed between Dec. 27, 2017, and Dec. 15, 2018. According to a release, the Food and Drug Administration has identified this recall as Class I, which is the most serious type of recall and indicates that “use of these devices may cause serious injuries or death.”

These strips are used by patients taking warfarin to help determine the patients’ international normalized ratio, which doctors and patients then use to decide whether the dose is appropriate. Roche Diagnostics, the strips’ manufacturer, issued a recall in September 2018; the test strips distributed by Terrific Care and Medex, however, were not labeled or authorized for sale in the United States and were therefore not included in that original recall. According to the release, the strips in this recall, which was initiated Dec. 21, 2018, were purchased by Terrific Care and Medex from an unknown source and then distributed in the United States. On Jan. 28, 2019, Terrific Care sent an Urgent Medical Device Recall Notification Letter to customers.

The full recall is described on the FDA website.
 

cpalmer@mdedge.com

A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.

©decade3d/Thinkstock

This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.

“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”

Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.

The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.

In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).

Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.

“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.

Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”

The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.

mlesney@mdedge.com

SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.

A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.

©decade3d/Thinkstock

This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.

“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”

Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.

The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.

In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).

Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.

“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.

Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”

The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.

mlesney@mdedge.com

SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.

A growing body of evidence suggests that, along with other vascular beds, smoking and chronic obstructive pulmonary disease (COPD) affect the arteries of the lower limbs in terms of the development of peripheral arterial disease (PAD), reported Karsten Keller, MD, of the Johannes Gutenberg-University Mainz (Germany) and his colleagues.

©decade3d/Thinkstock

This provided the rationale for their large database analysis of inpatients with concomitant COPD and PAD. They found that the additional presence of COPD was associated with increased in-hospital mortality in patients with PAD.

“Our data suggest that COPD increased the mortality of PAD patients by the factor 1.2-fold,” they wrote in Respiratory Medicine. “Unexpectedly, this increase was not driven by [myocardial infarction] as the life-threatening acute presentation of [coronary artery disease], but rather related to an increased risk for [pulmonary embolism] and a higher coprevalence of cancer.”

Dr. Keller and his colleagues inspected the German inpatient national database based on ICD codes. They identified 5,611,827 adult inpatients (64.8% men) diagnosed with PAD between January 2005 and December 2015, and of those, 13.6% also were coded for COPD. Overall, 277,894 PAD patients (5.0%) died in the hospital, Dr. Keller and his colleagues wrote.

The all-cause, in-hospital mortality was significantly higher in PAD patients with COPD, compared with those without COPD (6.5% vs. 4.7%, respectively; P less than .001), and cardiovascular events comprising pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) occurred more often in coprevalence with PAD and COPD than in PAD without COPD.

In PAD patients, COPD was an independent predictor of in-hospital death (odds ratio, 1.16; 95% confidence interval, 1.15-1.17; P less than .001) as well as an independent predictor for PE (OR, 1.44; 95% CI, 1.40-1.49; P less than .001).

Overall, PAD patients with COPD were of similar age as (73 years), but stayed slightly longer in the hospital than (9 vs. 8 days), those without COPD. PAD patients without COPD revealed more often cardiovascular risk factors like essential arterial hypertension and diabetes, but the prevalence of cardiovascular diseases such as coronary artery disease and heart failure were more often found in PAD patients with COPD. In addition, cancer and renal insufficiency also were more common in PAD patients with COPD, according to the authors.

“Remarkably, PAD patients with COPD showed more frequently lower PAD stages than those without COPD. Especially, PAD stage IV was more prevalent in PAD patients without COPD (19.6% vs. 13.8%; P less than 0.001),” the authors stated. In addition, amputations were more often performed in PAD patients without COPD.

Dr. Keller and his colleagues had the following conclusions regarding the clinical implications of their study: “I) PAD patients with long-standing tobacco use might benefit from COPD screening and treatment. II) PAD patients with additional COPD should be monitored more intensively, and the treatment for COPD should be optimized. III) COPD increases the risk for PE, and it is critical not to overlook this life-threatening disease. IV) MI and PE are important causes of in-hospital death in PAD patients with and without COPD.”

The German Federal Ministry of Education and Research funded the study, and the authors reported having no conflicts.

mlesney@mdedge.com

SOURCE: Keller K et al. Respir Med. 2019 Feb;147:1-6.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

jensmith@mdedge.com

SOURCE: McBane RD et al. ASH 2018, Abstract 421.

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

jensmith@mdedge.com

SOURCE: McBane RD et al. ASH 2018, Abstract 421.

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

jensmith@mdedge.com

SOURCE: McBane RD et al. ASH 2018, Abstract 421.