Thoracic Surgery News (Archived)

LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.

Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.

One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).

Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.

Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.

The primary safety endpoint was all-cause mortality within 30 days from the index procedure.

A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.

At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.

One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.

Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.

The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.

[email protected]

LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.

Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.

One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).

Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.

Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.

The primary safety endpoint was all-cause mortality within 30 days from the index procedure.

A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.

At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.

One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.

Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.

The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.

[email protected]

LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.

Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.

One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).

Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.

Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.

The primary safety endpoint was all-cause mortality within 30 days from the index procedure.

A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.

At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.

One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.

Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.

The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.

[email protected]

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.

In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.

The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.

Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.

They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.

The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.

In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).

Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).

However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).

It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.

The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.

The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.

Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.

This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.

This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.

The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.

Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.

They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.

The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.

In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).

Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).

However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).

It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.

The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.

The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.

Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.

This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.

This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

In patients undergoing transcatheter aortic valve implantation, use of a cerebral protection device to entrap and remove embolic debris reduced both the number and the size of ischemic brain lesions, according to a report published in JAMA.

The frequency and severity of postprocedure stroke symptoms were similar with and without the filter; however, the researchers noted that the study included only 100 patients and was not powered to assess differences in stroke rates.

Various cerebral protection devices were invented in response to the finding of a threefold increase in periprocedural stroke mortality following TAVI. Yet “clear evidence of the efficacy of any embolic protection device in TAVI is still missing,” said Stephan Haussig, MD, of the University of Leipzig (Germany) Heart Center, and his associates.

They performed a prospective randomized clinical trial at their center to assess the efficacy of the only cerebral protection device that was available when their study was designed. For the study, 100 patients with severe, symptomatic aortic stenosis were randomly assigned to undergo TAVI either with (50 patients) or without (50 patients) the use of a protective filter to capture embolic debris. The filter device was estimated to fully protect 74% of the brain and partially protect 24%, leaving only 2% unprotected.

The primary endpoint of the study was the number of ischemic brain lesions detected on diffusion-weighted MRI in the filter group, compared with the control group. This imaging was performed at baseline, 2 days after the procedure, and 7 days after the procedure.

In protected brain regions, the median number of new ischemic brain lesions was markedly lower in the filter group than in the control group (4 vs. 10) at 2 days, as well as at 7 days (3 vs. 7, respectively). In addition, the volume of new lesions in protected brain regions also was markedly lower in the filter group at 2 days (242 mm vs. 527 mm) and at 7 days (101 mm vs. 292 mm).

Similar protective effects were evident when the entire brain was evaluated. The median number of new lesions was markedly lower in the filter group than in the control group (8 vs. 16) at 2 days and at 7 days (5 vs. 10, respectively). The median lesion volume also was markedly lower in the filter group at 2 days (466 mm vs. 800 mm) and at 7 days (205 mm vs. 720 mm).

However, this protective effect didn’t translate into a substantive difference in neurologic outcomes between the two study groups, as assessed by the National Institutes of Health Stroke Scale and the modified Rankin scale. Five patients in each group developed symptoms of stroke, and all symptoms were deemed minor and nondisabling, the investigators said (JAMA 2016;316[6]:592-601).

It is important to note that this study wasn’t powered to assess differences in stroke rates. Larger studies will be needed to assess the impact of protective devices on neurological and functional outcomes, Dr. Haussig and his associates wrote.

The two study groups also did not differ with regard to complications. Thirty-day mortality was 0% in the filter group and 2% in the control group, a nonsignificant difference.

The investigators pointed out that protective filter devices can protect the brain only while they are in place during TAVI, “which usually takes less than 1 hour and represents only 2% of the first 48 hours after which the first MRI was performed in this study. Based on the analyzed material captured and removed by the filters – e.g., old and fresh thrombus, endothelium, atheromatous plaque, valve tissue, and calcium – it becomes evident that causes of cerebral injury are multifactorial and that the embolic risk does not resolve immediately at the end of the TAVI procedure,” they said.

Perhaps the study’s most surprising finding was that nearly every patient had new cerebral lesions consistent with infarcts, but most of these were very small and not associated with any neurocognitive or functional impairments.

This study was limited in that it involved a single cardiac team assessing only one brand of filter device at a single hospital, so the results are not necessarily generalizable to a broader patient population or to the many other devices that have since been developed, Dr. Haussig and his associates added.

This study was funded by a grant from Claret Medical and Medtronic. Dr. Haussig reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.

Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.

BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.

Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.

BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.

Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.

MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.

The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.

“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”

©Gio_tto/Thinkstock

It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).

However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).

“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.

To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.

MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A_1c. The project includes data on 133,000 subjects without type 2 diabetes.

They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.

MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.

He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.

In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.

A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).

The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.

Dr. Merino had no financial disclosures.

[email protected]

MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.

The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.

“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”

©Gio_tto/Thinkstock

It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).

However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).

“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.

To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.

MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A_1c. The project includes data on 133,000 subjects without type 2 diabetes.

They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.

MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.

He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.

In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.

A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).

The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.

Dr. Merino had no financial disclosures.

[email protected]

MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.

The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.

“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”

©Gio_tto/Thinkstock

It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).

However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).

“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.

To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.

MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A_1c. The project includes data on 133,000 subjects without type 2 diabetes.

They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.

MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.

He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.

In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.

A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).

The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.

Dr. Merino had no financial disclosures.

[email protected]

AATS welcomes you to submit your abstracts and videos to the 2017 Mitral Conclave.

AATS Mitral Conclave
April 27-28, 2017
New York, NY

Submission Deadline:
Sunday, January 8, 2017 @ 11.59 pm EST

Submit online

Share:

AATS welcomes you to submit your abstracts and videos to the 2017 Mitral Conclave.

AATS Mitral Conclave
April 27-28, 2017
New York, NY

Submission Deadline:
Sunday, January 8, 2017 @ 11.59 pm EST

Submit online

Share:

AATS welcomes you to submit your abstracts and videos to the 2017 Mitral Conclave.

AATS Mitral Conclave
April 27-28, 2017
New York, NY

Submission Deadline:
Sunday, January 8, 2017 @ 11.59 pm EST

Submit online

Share:

Current and future CT surgery division chiefs/department chairs are invited to apply for the AATS Leadership Academy Program.

Friday, April 28, 2017
AATS Centennial
Boston, MA

This intensive, didactic and interactive program brings together up to 20 international surgeons who have demonstrated significant promise as potential future division chiefs or have recent assumed that role. The program provides participants with administrative, interpersonal, mentoring and negotiating skills, as well as the opportunity to network with well-known thoracic surgeon leaders and potential mentors. 

Deadline: November 30, 2016

Qualifications/More Information 

Current and future CT surgery division chiefs/department chairs are invited to apply for the AATS Leadership Academy Program.

Friday, April 28, 2017
AATS Centennial
Boston, MA

This intensive, didactic and interactive program brings together up to 20 international surgeons who have demonstrated significant promise as potential future division chiefs or have recent assumed that role. The program provides participants with administrative, interpersonal, mentoring and negotiating skills, as well as the opportunity to network with well-known thoracic surgeon leaders and potential mentors. 

Deadline: November 30, 2016

Qualifications/More Information 

Current and future CT surgery division chiefs/department chairs are invited to apply for the AATS Leadership Academy Program.

Friday, April 28, 2017
AATS Centennial
Boston, MA

This intensive, didactic and interactive program brings together up to 20 international surgeons who have demonstrated significant promise as potential future division chiefs or have recent assumed that role. The program provides participants with administrative, interpersonal, mentoring and negotiating skills, as well as the opportunity to network with well-known thoracic surgeon leaders and potential mentors. 

Deadline: November 30, 2016

Qualifications/More Information 

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.

Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).

©PhotoDisk

The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.

Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.

In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.

“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.

The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.

The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.

Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.

Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).

©PhotoDisk

The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.

Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.

In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.

“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.

The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.

The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.

Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.

Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).

©PhotoDisk

The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.

Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.

In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.

“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.

The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.

The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.

ORLANDO – Use of sacubitril/valsartan to treat patients with heart failure with reduced ejection fraction (HFrEF) became a class I recommendation in both the U.S. and European heart failure guidelines in May 2016, but virtually all U.S. health insurers continue to regard the potent and effective sacubitril/valsartan formulation as a second-line treatment that needs special preauthorization before patients receive reimbursement for the prescription.

“What is really morally sad is that U.S. payers are requiring physicians to fill out extensive, patient-by-patient paperwork” to allow patients with HFrEF to receive health insurance coverage for sacubitril/valsartan (Entresto), Milton Packer, MD, said at the annual scientific meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

“It is very difficult to understand why third-party payers would intentionally try to slow adoption of this life-saving drug simply because it is considered expensive. It is much cheaper than many drugs they cover for patients with cancer that don’t work half as well,” said Dr. Packer, a cardiologist and heart failure specialist at Baylor University Medical Center in Dallas.

The “excessive paperwork” for insurers when starting patients on sacubitril/valsartan is a “new and unique phenomenon among the cardiovascular drugs I prescribe,” agreed Nancy K. Sweitzer, MD, PhD, professor and chief of cardiology at the University of Arizona in Tuscon. “This approach by insurers seems based on cost; they do not want to pay” for sacubitril/valsartan, and to successfully arrange for coverage patients need to exactly match the enrollment criteria used in the PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor – Neprilysin Inhibitor] with ACEI [Angiotensin-Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial ), the pivotal study that supplied the evidence base for making sacubitril/valsartan a class I agent for treating HFrEF.

“I don’t put some HFrEF patients on sacubitil/valsartan just because they don’t meet the trial’s entry criteria,” Dr. Sweitzer said in an interview. “Insurers seem to scrutinize every single parameter to make sure patients match the PARADIGM-HF patients. Coverage is denied if their BNP [brain natriuretic peptide] level is too low.” Dr. Sweitzer added that in one instance she had to submit a second preauthorization to simply uptitrate the dosage of sacubitril/valsartan she wanted a patient to receive.

“Based on the data it seems like you could easily identify HFrEF patients who are good candidates for sacubitril/valsartan, but your hands are tied by payers because you can’t prescribe it until you’ve first tried something else, and even then you still need to deal with a lot of paperwork,” agreed Robert O. Bonow, MD, professor of medicine at Northwestern University in Chicago. “The paperwork burden is really cumbersome for physicians with busy practices; it impedes taking care of patients,” Dr. Bonow said in an interview.

Sales figures for sacubitril/valsartan that the drug’s manufacturer, Novartis, has reported since the agent received U.S. marketing approval a little over a year ago reflect these challenges in prescribing the compound to patients. During the first quarter of 2016, Novartis reported $17 million in worldwide sales of the agent, followed by $32 million in worldwide sales during the second quarter of 2016, through June 30. With a total of $49 million in sacubitril/valsartan sales during the first 6 months of 2016, it seems like Novartis may be challenged to meet its stated target of $200 million in total sales of the compound during 2016. In April, one commentator called the $17 million sales figure for first quarter 2016 “an astonishingly small amount for a drug that was widely expected to be a blockbuster.”

Dr. Packer has in the past been a consultant to Novartis and was one of the lead investigators for the PARADIGM-HF trial. He said that currently he has no financial relationship with Novartis but he does serve as a consultant to several other drug companies. Dr. Sweitzer has received research support from Novartis and was an investigator for PARADIGM-HF. Dr. Bonow has been a consultant to Gilead.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Use of sacubitril/valsartan to treat patients with heart failure with reduced ejection fraction (HFrEF) became a class I recommendation in both the U.S. and European heart failure guidelines in May 2016, but virtually all U.S. health insurers continue to regard the potent and effective sacubitril/valsartan formulation as a second-line treatment that needs special preauthorization before patients receive reimbursement for the prescription.

“What is really morally sad is that U.S. payers are requiring physicians to fill out extensive, patient-by-patient paperwork” to allow patients with HFrEF to receive health insurance coverage for sacubitril/valsartan (Entresto), Milton Packer, MD, said at the annual scientific meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

“It is very difficult to understand why third-party payers would intentionally try to slow adoption of this life-saving drug simply because it is considered expensive. It is much cheaper than many drugs they cover for patients with cancer that don’t work half as well,” said Dr. Packer, a cardiologist and heart failure specialist at Baylor University Medical Center in Dallas.

The “excessive paperwork” for insurers when starting patients on sacubitril/valsartan is a “new and unique phenomenon among the cardiovascular drugs I prescribe,” agreed Nancy K. Sweitzer, MD, PhD, professor and chief of cardiology at the University of Arizona in Tuscon. “This approach by insurers seems based on cost; they do not want to pay” for sacubitril/valsartan, and to successfully arrange for coverage patients need to exactly match the enrollment criteria used in the PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor – Neprilysin Inhibitor] with ACEI [Angiotensin-Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial ), the pivotal study that supplied the evidence base for making sacubitril/valsartan a class I agent for treating HFrEF.

“I don’t put some HFrEF patients on sacubitil/valsartan just because they don’t meet the trial’s entry criteria,” Dr. Sweitzer said in an interview. “Insurers seem to scrutinize every single parameter to make sure patients match the PARADIGM-HF patients. Coverage is denied if their BNP [brain natriuretic peptide] level is too low.” Dr. Sweitzer added that in one instance she had to submit a second preauthorization to simply uptitrate the dosage of sacubitril/valsartan she wanted a patient to receive.

“Based on the data it seems like you could easily identify HFrEF patients who are good candidates for sacubitril/valsartan, but your hands are tied by payers because you can’t prescribe it until you’ve first tried something else, and even then you still need to deal with a lot of paperwork,” agreed Robert O. Bonow, MD, professor of medicine at Northwestern University in Chicago. “The paperwork burden is really cumbersome for physicians with busy practices; it impedes taking care of patients,” Dr. Bonow said in an interview.

Sales figures for sacubitril/valsartan that the drug’s manufacturer, Novartis, has reported since the agent received U.S. marketing approval a little over a year ago reflect these challenges in prescribing the compound to patients. During the first quarter of 2016, Novartis reported $17 million in worldwide sales of the agent, followed by $32 million in worldwide sales during the second quarter of 2016, through June 30. With a total of $49 million in sacubitril/valsartan sales during the first 6 months of 2016, it seems like Novartis may be challenged to meet its stated target of $200 million in total sales of the compound during 2016. In April, one commentator called the $17 million sales figure for first quarter 2016 “an astonishingly small amount for a drug that was widely expected to be a blockbuster.”

Dr. Packer has in the past been a consultant to Novartis and was one of the lead investigators for the PARADIGM-HF trial. He said that currently he has no financial relationship with Novartis but he does serve as a consultant to several other drug companies. Dr. Sweitzer has received research support from Novartis and was an investigator for PARADIGM-HF. Dr. Bonow has been a consultant to Gilead.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Use of sacubitril/valsartan to treat patients with heart failure with reduced ejection fraction (HFrEF) became a class I recommendation in both the U.S. and European heart failure guidelines in May 2016, but virtually all U.S. health insurers continue to regard the potent and effective sacubitril/valsartan formulation as a second-line treatment that needs special preauthorization before patients receive reimbursement for the prescription.

“What is really morally sad is that U.S. payers are requiring physicians to fill out extensive, patient-by-patient paperwork” to allow patients with HFrEF to receive health insurance coverage for sacubitril/valsartan (Entresto), Milton Packer, MD, said at the annual scientific meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

“It is very difficult to understand why third-party payers would intentionally try to slow adoption of this life-saving drug simply because it is considered expensive. It is much cheaper than many drugs they cover for patients with cancer that don’t work half as well,” said Dr. Packer, a cardiologist and heart failure specialist at Baylor University Medical Center in Dallas.

The “excessive paperwork” for insurers when starting patients on sacubitril/valsartan is a “new and unique phenomenon among the cardiovascular drugs I prescribe,” agreed Nancy K. Sweitzer, MD, PhD, professor and chief of cardiology at the University of Arizona in Tuscon. “This approach by insurers seems based on cost; they do not want to pay” for sacubitril/valsartan, and to successfully arrange for coverage patients need to exactly match the enrollment criteria used in the PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor – Neprilysin Inhibitor] with ACEI [Angiotensin-Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial ), the pivotal study that supplied the evidence base for making sacubitril/valsartan a class I agent for treating HFrEF.

“I don’t put some HFrEF patients on sacubitil/valsartan just because they don’t meet the trial’s entry criteria,” Dr. Sweitzer said in an interview. “Insurers seem to scrutinize every single parameter to make sure patients match the PARADIGM-HF patients. Coverage is denied if their BNP [brain natriuretic peptide] level is too low.” Dr. Sweitzer added that in one instance she had to submit a second preauthorization to simply uptitrate the dosage of sacubitril/valsartan she wanted a patient to receive.

“Based on the data it seems like you could easily identify HFrEF patients who are good candidates for sacubitril/valsartan, but your hands are tied by payers because you can’t prescribe it until you’ve first tried something else, and even then you still need to deal with a lot of paperwork,” agreed Robert O. Bonow, MD, professor of medicine at Northwestern University in Chicago. “The paperwork burden is really cumbersome for physicians with busy practices; it impedes taking care of patients,” Dr. Bonow said in an interview.

Sales figures for sacubitril/valsartan that the drug’s manufacturer, Novartis, has reported since the agent received U.S. marketing approval a little over a year ago reflect these challenges in prescribing the compound to patients. During the first quarter of 2016, Novartis reported $17 million in worldwide sales of the agent, followed by $32 million in worldwide sales during the second quarter of 2016, through June 30. With a total of $49 million in sacubitril/valsartan sales during the first 6 months of 2016, it seems like Novartis may be challenged to meet its stated target of $200 million in total sales of the compound during 2016. In April, one commentator called the $17 million sales figure for first quarter 2016 “an astonishingly small amount for a drug that was widely expected to be a blockbuster.”

Dr. Packer has in the past been a consultant to Novartis and was one of the lead investigators for the PARADIGM-HF trial. He said that currently he has no financial relationship with Novartis but he does serve as a consultant to several other drug companies. Dr. Sweitzer has received research support from Novartis and was an investigator for PARADIGM-HF. Dr. Bonow has been a consultant to Gilead.

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