Anticoagulation Hub

Americans could see improvements in their quality of life and life expectancy if more of them utilize personalized and precision medicine (PPM), according to an opinion piece by Dr. Victor J. Dzau, president of the Institute of Medicine, Washington, D.C., and his colleagues.

“Applications of personalized and precision medicine aimed at prevention have the potential to generate substantial value for society,” the authors wrote.

This opinion is based on the authors’ analysis of an assessment of the benefits and costs of PPM innovations designed to improve screening and risk-factor stratification technologies for identifying presymptomatic individuals at high risk for specific diseases. Dr. Dzau and his associates assumed that the preventive PPM interventions permanently reduced the incidence of cancer, diabetes, heart disease, hypertension, lung disease, and stroke by a fixed percentage beginning in 2012 and needed to be sustained over a lifetime. Benefits were computed by looking at life expectancy and quality-adjusted life expectancy gains during the subsequent 50 years. Values of health were expressed in dollars using $100,000 per quality-adjusted life year.

According to the assessment performed with the Health Economics Medical Innovation Simulation, a PPM innovation that reduced the incidence of the six aforementioned diseases by 10% would generate between $33 billion and $114 billion per disease in the form of longer lives. When the incidence of the diseases was reduced by 50%, the values of health generated ranged from $161 billion to $607 billion. In both scenarios, reductions in heart disease generated the highest number of quality-adjusted life years.

Dr. Dzau and his associates acknowledged that “PPM treatments that might generate less value overall, but provide greater short-term returns” are favored in the current reimbursement environment.

Read the full paper in the Lancet (2015 [doi:10.1016/S0140-6736(15)60722-X]).

Americans could see improvements in their quality of life and life expectancy if more of them utilize personalized and precision medicine (PPM), according to an opinion piece by Dr. Victor J. Dzau, president of the Institute of Medicine, Washington, D.C., and his colleagues.

“Applications of personalized and precision medicine aimed at prevention have the potential to generate substantial value for society,” the authors wrote.

This opinion is based on the authors’ analysis of an assessment of the benefits and costs of PPM innovations designed to improve screening and risk-factor stratification technologies for identifying presymptomatic individuals at high risk for specific diseases. Dr. Dzau and his associates assumed that the preventive PPM interventions permanently reduced the incidence of cancer, diabetes, heart disease, hypertension, lung disease, and stroke by a fixed percentage beginning in 2012 and needed to be sustained over a lifetime. Benefits were computed by looking at life expectancy and quality-adjusted life expectancy gains during the subsequent 50 years. Values of health were expressed in dollars using $100,000 per quality-adjusted life year.

According to the assessment performed with the Health Economics Medical Innovation Simulation, a PPM innovation that reduced the incidence of the six aforementioned diseases by 10% would generate between $33 billion and $114 billion per disease in the form of longer lives. When the incidence of the diseases was reduced by 50%, the values of health generated ranged from $161 billion to $607 billion. In both scenarios, reductions in heart disease generated the highest number of quality-adjusted life years.

Dr. Dzau and his associates acknowledged that “PPM treatments that might generate less value overall, but provide greater short-term returns” are favored in the current reimbursement environment.

Read the full paper in the Lancet (2015 [doi:10.1016/S0140-6736(15)60722-X]).

Americans could see improvements in their quality of life and life expectancy if more of them utilize personalized and precision medicine (PPM), according to an opinion piece by Dr. Victor J. Dzau, president of the Institute of Medicine, Washington, D.C., and his colleagues.

“Applications of personalized and precision medicine aimed at prevention have the potential to generate substantial value for society,” the authors wrote.

This opinion is based on the authors’ analysis of an assessment of the benefits and costs of PPM innovations designed to improve screening and risk-factor stratification technologies for identifying presymptomatic individuals at high risk for specific diseases. Dr. Dzau and his associates assumed that the preventive PPM interventions permanently reduced the incidence of cancer, diabetes, heart disease, hypertension, lung disease, and stroke by a fixed percentage beginning in 2012 and needed to be sustained over a lifetime. Benefits were computed by looking at life expectancy and quality-adjusted life expectancy gains during the subsequent 50 years. Values of health were expressed in dollars using $100,000 per quality-adjusted life year.

According to the assessment performed with the Health Economics Medical Innovation Simulation, a PPM innovation that reduced the incidence of the six aforementioned diseases by 10% would generate between $33 billion and $114 billion per disease in the form of longer lives. When the incidence of the diseases was reduced by 50%, the values of health generated ranged from $161 billion to $607 billion. In both scenarios, reductions in heart disease generated the highest number of quality-adjusted life years.

Dr. Dzau and his associates acknowledged that “PPM treatments that might generate less value overall, but provide greater short-term returns” are favored in the current reimbursement environment.

Read the full paper in the Lancet (2015 [doi:10.1016/S0140-6736(15)60722-X]).

SEATTLE – The presentation of the late-breaking HISTORIC-AF Trial by Dr. Claudio Muneretto and his colleagues “is a very interesting one, which brings to the table a very different approach of hybrid procedures to treat stand-alone atrial fibrillation,” said Dr. Niv Ad of Inova Heart and Vascular Institute, Falls Church, Va.

Dr. Ad gave his comments in a video interview at the annual meeting of the American Association for Thoracic Surgery.

In his assessment, Dr. Ad noted that such studies are useful and can stimulate discussion, even if he would prefer a prospective, comparative study of all procedures. “I hope someday we can create an algorithm where everything has a place: catheter ablation, hybrid procedures where you do catheter ablation and surgical procedure together or in stage, and the stand-alone Maze procedure on pump,” Dr. Ad said.

[email protected]

SEATTLE – The presentation of the late-breaking HISTORIC-AF Trial by Dr. Claudio Muneretto and his colleagues “is a very interesting one, which brings to the table a very different approach of hybrid procedures to treat stand-alone atrial fibrillation,” said Dr. Niv Ad of Inova Heart and Vascular Institute, Falls Church, Va.

Dr. Ad gave his comments in a video interview at the annual meeting of the American Association for Thoracic Surgery.

In his assessment, Dr. Ad noted that such studies are useful and can stimulate discussion, even if he would prefer a prospective, comparative study of all procedures. “I hope someday we can create an algorithm where everything has a place: catheter ablation, hybrid procedures where you do catheter ablation and surgical procedure together or in stage, and the stand-alone Maze procedure on pump,” Dr. Ad said.

[email protected]

SEATTLE – The presentation of the late-breaking HISTORIC-AF Trial by Dr. Claudio Muneretto and his colleagues “is a very interesting one, which brings to the table a very different approach of hybrid procedures to treat stand-alone atrial fibrillation,” said Dr. Niv Ad of Inova Heart and Vascular Institute, Falls Church, Va.

Dr. Ad gave his comments in a video interview at the annual meeting of the American Association for Thoracic Surgery.

In his assessment, Dr. Ad noted that such studies are useful and can stimulate discussion, even if he would prefer a prospective, comparative study of all procedures. “I hope someday we can create an algorithm where everything has a place: catheter ablation, hybrid procedures where you do catheter ablation and surgical procedure together or in stage, and the stand-alone Maze procedure on pump,” Dr. Ad said.

[email protected]

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.

These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.

That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.

The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).

At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.

Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.

The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.

Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.

The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.

Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.

“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.

In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.

The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.

Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.

The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.

[email protected]

SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.

These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.

That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.

The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).

At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.

Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.

The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.

Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.

The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.

Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.

“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.

In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.

The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.

Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.

The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.

[email protected]

SAN DIEGO– A fuller picture of the benefits of vorapaxar for secondary cardiovascular prevention emerged from three separate secondary analyses of the pivotal Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P TIMI-50) trial presented at the annual meeting of the American College of Cardiology.

These new reports provided evidence that vorapaxar (Zontivity), a first-in-class, once-daily thrombin inhibitor with rapid onset and a half-life in excess of 7 days, reduces acute limb ischemia and the need for peripheral revascularization in patients with peripheral arterial disease (PAD), and also that the antiplatelet agent is particularly beneficial in patients with a history of coronary artery bypass graft surgery.

That being said, the three secondary analyses were post hoc and as such are inherently exploratory and hypothesis-generating rather than definitive, the investigators noted.

The Food and Drug Administration approved vorapaxar in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of MI or in patients with PAD in the absence of a previous stroke or TIA. Marketing approval was based chiefly on the results of the landmark 26,449-patient, double-blind, prospective, multinational TIMI 50 trial. In an analysis of the 20,170 randomized patients without a prior stroke or TIA, vorapaxar at 2.5 mg once daily, when added to standard therapy with aspirin and/or clopidogrel, reduced the 3-year rate of a composite outcome – comprised of cardiovascular death, MI, or stroke – by 20% compared with placebo, with a number-needed-to-treat of 63 (J. Am. Heart Assoc. 2015 [doi: 10.1161/JAHA.114.001505]).

At ACC 15, Dr. Ethan C. Kosova presented a subanalysis involving the 2,942 TIMI 50 participants who had undergone CABG surgery prior to the study. The rationale for taking a closer look at this group is that rates of venous graft occlusion and recurrent ischemic events remain high after CABG surgery, so the efficacy and safety of vorapaxar in this population are of particular interest.

Underscoring the high-risk nature of this population, at baseline the patients with a history of CABG were significantly older and had higher rates of hypertension, dyslipidemia, diabetes, PAD, heart failure, and chronic kidney disease than participants without prior CABG who had no history of stroke or TIA, observed Dr. Kosova of Brigham and Women’s Hospital, Boston.

The 3-year composite event rate of cardiovascular death, MI, or stroke occurred in 11.9% of the 1,471 patients with prior CABG who were randomized to vorapaxar compared with 15.6% of those on placebo. That translates into a 29% relative risk reduction and a number-needed-to-treat of 27, an even stronger result than in the general study population.

Moreover, the clinically relevant composite outcome consisting of cardiovascular death or MI occurred in 10.9% of those on vorapaxar compared with 14.3% of controls, for a 29% relative risk reduction and a number-needed-to-treat of 29, he continued.

The 3-year all-cause mortality was 5.8% in patients with prior CABG who received vorapaxar compared to 8% in those on placebo.

Vorapaxar, which inhibits protease-activated receptor-1 on platelets and vascular endothelium, increased the rate of GUSTO moderate-to-severe bleeding: 6.8% compared with 3.7% in controls.

“Putting together the efficacy and safety data to derive the net clinical outcome – the combined endpoint of all-cause mortality, MI, cerebrovascular accident, and GUSTO severe bleeding – the result was a 28% improvement with vorapaxar compared with placebo,” Dr. Kosova said.

In a separate presentation focused on the 3,787 patients who gained entry into the TIMI 50 trial on the basis of symptomatic PAD, Dr. Antonio Gutierrez reported that acute limb ischemia occurred in 109 of them during the trial. Fifty-four percent of these events were due to acute surgical graft thrombosis, 27% to in situ thrombosis of a native vessel, and lesser numbers were due to thromboembolissm or stent thrombosis.

The 3-year acute limb ischemia rate in patients with baseline PAD was 3.9% with placebo compared to 2.3% with vorapaxar, for a 42% relative risk reduction, according to Dr. Gutierrez of Brigham and Women’s Hospital.

Dr. Ian Gilchrist, also from Brigham and Women’s Hospital, reported that in TIMI 50 participants with a history of PAD, vorapaxar resulted in a 16% reduction in the need for peripheral revascularization procedures for claudication, with rates of 9.4% for vorapaxar and 11.6% for placebo. There was also a statistically significant 41% reduction in the rate of surgical peripheral revascularization procedures, with rates of 4.5% for vorapaxar and 7.7% for placebo.

The TIMI 50 trial was funded by Merck. Drs. Kosova, Gutierrez, and Gilchrist reported having no financial conflicts of interest.

[email protected]

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

SAN DIEGO – Remote ischemic preconditioning failed to improve long-term clinical outcomes in higher-risk patients undergoing coronary artery bypass surgery in the ERICCA trial.

At 1 year, there were no differences between patients receiving remote ischemic conditioning (RIC) or a sham procedure in the combined primary endpoint of cardiovascular death, MI, stroke, and coronary revascularization (27% vs. 28%) or its individual components.

Ingram Publishing/ thinkstockphotos.com

Only the extent of perioperative myocardial injury, measured as area under the curve troponin T levels, at 72 hours was significantly lower with RIC (median 30.1 ng.h/mL vs. 35.7 ng.h/mL), principal investigator Dr. Derek Hausenloy reported at the annual meeting of the American College of Cardiology.

The simple, low-cost intervention consisted of four 5-minute blood pressure cuff inflations to 200 mm Hg and deflations immediately before patients went on bypass.

Multiple proof-of-concept studies have shown that brief, reversible episodes of ischemia followed by reperfusion reduces the extent of perioperative myocardial injury in patients undergoing elective coronary artery stenting or bypass grafting.

“In the setting of cardiac bypass surgery, the cardioprotective effect presented by RIC, or remote ischemic conditioning, may be affected by factors during surgery,” said Dr. Hausenloy of University College, London.

There are multiple causes of injury in patients undergoing bypass that include not only myocardial reperfusion injury, but also coronary microembolization, inflammation as the patient is taken on and off bypass, and direct injury to the heart, he noted.

ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery) also focused on a higher-risk aged population (76 years) with high rates of comorbidities like diabetes (25%) and hypertension (75%) that have been shown to impact RIC and other conditioning strategies.

Discussant Dr. Richard Fogel of St. Vincent Heart Center in Indianapolis, suggested RIC may not have worked because of a dose-response issue and questioned whether the results would have been different had the investigators, for example, done six inflations for 10 minutes each or performed RIC the day before.

Discussant Dr. Eric Bates of the University of Michigan in Ann Arbor, suggested that as long as patients are anesthetized, prolonged conditioning immediately before and after surgery might be considered.

“The RIC protocol has not been very well characterized, although most of the prior studies used three or four cycles,” Dr. Hausenloy said. “Whether this is the optimal stimulus is not known or clear.”

ERICCA enrolled 1,612 patients with an additive Euroscore of at least 5 who underwent CABG using blood cardioplegia at 29 centers in the United Kingdom. Of these, 801 received RIC and 811 received sham, simulated BP cuff inflations/deflations.

One year after surgery, the RIC and control groups had similar rates of major adverse cardiac and cerebral events, at 26.7% and 27.7%, respectively; cardiovascular death, at 5.9% and 3.9%; MI, at 21.8% and 23.7%; stroke, at 2.1% and 2.0%; and revascularization, at 0.2% and 0.4%.

“It’s interesting that we show a modest effect on reducing perioperative myocardial injury, but we didn’t see any associated improvement in clinical outcome,” he said. “This may question the use of perioperative myocardial injury, as measured by serum biomarkers, as a surrogate marker of cardioprotection. However, the caveat is that we only have a complete dataset for this conclusion in half the patients.”

The potential effect of RIC remains to be investigated in other settings of ischemia and reperfusion injury such as patients with ST-segment elevation MI or undergoing organ transplantation, Dr. Hausenloy said.

“Clearly in these settings of STEMI and organ transplantation, the contribution of ischemia reperfusion injury is greater, and one may speculate that the effect of RIC may be greater,” he added.

[email protected]

SAN DIEGO – Remote ischemic preconditioning failed to improve long-term clinical outcomes in higher-risk patients undergoing coronary artery bypass surgery in the ERICCA trial.

At 1 year, there were no differences between patients receiving remote ischemic conditioning (RIC) or a sham procedure in the combined primary endpoint of cardiovascular death, MI, stroke, and coronary revascularization (27% vs. 28%) or its individual components.

Ingram Publishing/ thinkstockphotos.com

Only the extent of perioperative myocardial injury, measured as area under the curve troponin T levels, at 72 hours was significantly lower with RIC (median 30.1 ng.h/mL vs. 35.7 ng.h/mL), principal investigator Dr. Derek Hausenloy reported at the annual meeting of the American College of Cardiology.

The simple, low-cost intervention consisted of four 5-minute blood pressure cuff inflations to 200 mm Hg and deflations immediately before patients went on bypass.

Multiple proof-of-concept studies have shown that brief, reversible episodes of ischemia followed by reperfusion reduces the extent of perioperative myocardial injury in patients undergoing elective coronary artery stenting or bypass grafting.

“In the setting of cardiac bypass surgery, the cardioprotective effect presented by RIC, or remote ischemic conditioning, may be affected by factors during surgery,” said Dr. Hausenloy of University College, London.

There are multiple causes of injury in patients undergoing bypass that include not only myocardial reperfusion injury, but also coronary microembolization, inflammation as the patient is taken on and off bypass, and direct injury to the heart, he noted.

ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery) also focused on a higher-risk aged population (76 years) with high rates of comorbidities like diabetes (25%) and hypertension (75%) that have been shown to impact RIC and other conditioning strategies.

Discussant Dr. Richard Fogel of St. Vincent Heart Center in Indianapolis, suggested RIC may not have worked because of a dose-response issue and questioned whether the results would have been different had the investigators, for example, done six inflations for 10 minutes each or performed RIC the day before.

Discussant Dr. Eric Bates of the University of Michigan in Ann Arbor, suggested that as long as patients are anesthetized, prolonged conditioning immediately before and after surgery might be considered.

“The RIC protocol has not been very well characterized, although most of the prior studies used three or four cycles,” Dr. Hausenloy said. “Whether this is the optimal stimulus is not known or clear.”

ERICCA enrolled 1,612 patients with an additive Euroscore of at least 5 who underwent CABG using blood cardioplegia at 29 centers in the United Kingdom. Of these, 801 received RIC and 811 received sham, simulated BP cuff inflations/deflations.

One year after surgery, the RIC and control groups had similar rates of major adverse cardiac and cerebral events, at 26.7% and 27.7%, respectively; cardiovascular death, at 5.9% and 3.9%; MI, at 21.8% and 23.7%; stroke, at 2.1% and 2.0%; and revascularization, at 0.2% and 0.4%.

“It’s interesting that we show a modest effect on reducing perioperative myocardial injury, but we didn’t see any associated improvement in clinical outcome,” he said. “This may question the use of perioperative myocardial injury, as measured by serum biomarkers, as a surrogate marker of cardioprotection. However, the caveat is that we only have a complete dataset for this conclusion in half the patients.”

The potential effect of RIC remains to be investigated in other settings of ischemia and reperfusion injury such as patients with ST-segment elevation MI or undergoing organ transplantation, Dr. Hausenloy said.

“Clearly in these settings of STEMI and organ transplantation, the contribution of ischemia reperfusion injury is greater, and one may speculate that the effect of RIC may be greater,” he added.

[email protected]

SAN DIEGO – Remote ischemic preconditioning failed to improve long-term clinical outcomes in higher-risk patients undergoing coronary artery bypass surgery in the ERICCA trial.

At 1 year, there were no differences between patients receiving remote ischemic conditioning (RIC) or a sham procedure in the combined primary endpoint of cardiovascular death, MI, stroke, and coronary revascularization (27% vs. 28%) or its individual components.

Ingram Publishing/ thinkstockphotos.com

Only the extent of perioperative myocardial injury, measured as area under the curve troponin T levels, at 72 hours was significantly lower with RIC (median 30.1 ng.h/mL vs. 35.7 ng.h/mL), principal investigator Dr. Derek Hausenloy reported at the annual meeting of the American College of Cardiology.

The simple, low-cost intervention consisted of four 5-minute blood pressure cuff inflations to 200 mm Hg and deflations immediately before patients went on bypass.

Multiple proof-of-concept studies have shown that brief, reversible episodes of ischemia followed by reperfusion reduces the extent of perioperative myocardial injury in patients undergoing elective coronary artery stenting or bypass grafting.

“In the setting of cardiac bypass surgery, the cardioprotective effect presented by RIC, or remote ischemic conditioning, may be affected by factors during surgery,” said Dr. Hausenloy of University College, London.

There are multiple causes of injury in patients undergoing bypass that include not only myocardial reperfusion injury, but also coronary microembolization, inflammation as the patient is taken on and off bypass, and direct injury to the heart, he noted.

ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery) also focused on a higher-risk aged population (76 years) with high rates of comorbidities like diabetes (25%) and hypertension (75%) that have been shown to impact RIC and other conditioning strategies.

Discussant Dr. Richard Fogel of St. Vincent Heart Center in Indianapolis, suggested RIC may not have worked because of a dose-response issue and questioned whether the results would have been different had the investigators, for example, done six inflations for 10 minutes each or performed RIC the day before.

Discussant Dr. Eric Bates of the University of Michigan in Ann Arbor, suggested that as long as patients are anesthetized, prolonged conditioning immediately before and after surgery might be considered.

“The RIC protocol has not been very well characterized, although most of the prior studies used three or four cycles,” Dr. Hausenloy said. “Whether this is the optimal stimulus is not known or clear.”

ERICCA enrolled 1,612 patients with an additive Euroscore of at least 5 who underwent CABG using blood cardioplegia at 29 centers in the United Kingdom. Of these, 801 received RIC and 811 received sham, simulated BP cuff inflations/deflations.

One year after surgery, the RIC and control groups had similar rates of major adverse cardiac and cerebral events, at 26.7% and 27.7%, respectively; cardiovascular death, at 5.9% and 3.9%; MI, at 21.8% and 23.7%; stroke, at 2.1% and 2.0%; and revascularization, at 0.2% and 0.4%.

“It’s interesting that we show a modest effect on reducing perioperative myocardial injury, but we didn’t see any associated improvement in clinical outcome,” he said. “This may question the use of perioperative myocardial injury, as measured by serum biomarkers, as a surrogate marker of cardioprotection. However, the caveat is that we only have a complete dataset for this conclusion in half the patients.”

The potential effect of RIC remains to be investigated in other settings of ischemia and reperfusion injury such as patients with ST-segment elevation MI or undergoing organ transplantation, Dr. Hausenloy said.

“Clearly in these settings of STEMI and organ transplantation, the contribution of ischemia reperfusion injury is greater, and one may speculate that the effect of RIC may be greater,” he added.

[email protected]

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care, investigators reported in Academic Emergency Medicine.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr. Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.

“The results of this analysis provide further support that risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department (Acad. Emerg. Med. 2015;22:299-307).”

The PESI has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The simplified PESI has 6 of the PESI’s 11 variables, but remains accurate in assessing PE severity, the researchers said. They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the phase III Einstein PE study, in which rivaroxaban was found noninferior to an enoxaparin–vitamin K antagonist combination in terms of the risk of recurrent venous thromboembolism and clinically important bleeding events (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received.

However, the incidence of major bleeds up to 30 days was lower in the rivaroxaban group than in the standard treatment group, especially if patients’ simplified PESI scores were greater than 0. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding at all time points and in both treatment groups.

Bayer HealthCare Pharmaceuticals and Janssen Research & Development funded the study. Dr. Fermann reported an advisory relationship with Janssen and research funding from Cardiorentis, Trevena, Novartis, Siemens, and Pfizer. Two coauthors reported employment with Bayer, and two other coauthors reported financial and advisory relationships with several other pharmaceutical companies.

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care, investigators reported in Academic Emergency Medicine.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr. Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.

“The results of this analysis provide further support that risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department (Acad. Emerg. Med. 2015;22:299-307).”

The PESI has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The simplified PESI has 6 of the PESI’s 11 variables, but remains accurate in assessing PE severity, the researchers said. They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the phase III Einstein PE study, in which rivaroxaban was found noninferior to an enoxaparin–vitamin K antagonist combination in terms of the risk of recurrent venous thromboembolism and clinically important bleeding events (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received.

However, the incidence of major bleeds up to 30 days was lower in the rivaroxaban group than in the standard treatment group, especially if patients’ simplified PESI scores were greater than 0. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding at all time points and in both treatment groups.

Bayer HealthCare Pharmaceuticals and Janssen Research & Development funded the study. Dr. Fermann reported an advisory relationship with Janssen and research funding from Cardiorentis, Trevena, Novartis, Siemens, and Pfizer. Two coauthors reported employment with Bayer, and two other coauthors reported financial and advisory relationships with several other pharmaceutical companies.

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care, investigators reported in Academic Emergency Medicine.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr. Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.

“The results of this analysis provide further support that risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department (Acad. Emerg. Med. 2015;22:299-307).”

The PESI has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The simplified PESI has 6 of the PESI’s 11 variables, but remains accurate in assessing PE severity, the researchers said. They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the phase III Einstein PE study, in which rivaroxaban was found noninferior to an enoxaparin–vitamin K antagonist combination in terms of the risk of recurrent venous thromboembolism and clinically important bleeding events (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received.

However, the incidence of major bleeds up to 30 days was lower in the rivaroxaban group than in the standard treatment group, especially if patients’ simplified PESI scores were greater than 0. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding at all time points and in both treatment groups.

Bayer HealthCare Pharmaceuticals and Janssen Research & Development funded the study. Dr. Fermann reported an advisory relationship with Janssen and research funding from Cardiorentis, Trevena, Novartis, Siemens, and Pfizer. Two coauthors reported employment with Bayer, and two other coauthors reported financial and advisory relationships with several other pharmaceutical companies.

More than 80% of patients with lower-extremity deep venous thrombosis who underwent endovascular treatment with the Angiojet rheolytic thrombectomy system were free of rethrombosis a year later, based on final results from the PEARL registry study.

Almost 4% of patients had bleeding events after treatment, but none of these events was tied to use of the Angiojet system, reported Dr. Mark Garcia of Mount Sinai Medical Center in New York and his associates.

Image provided courtesy of Boston Scientific. © 2015 Boston Scientific Corporation or its affiliates. All rights reserved.

“PEARL registry data demonstrate that rheolytic pharmacomechanical catheter-directed thrombolysis treatment of deep venous thrombosis is safe and effective, and can potentially reduce the need for concomitant catheter-directed thrombolysis and intensive care,” the researchers wrote.

The rates of venous thromboembolism are rising, and the number of affected adults is expected to double in the next 40 years as the population ages and experiences recurrent episodes. Lower-extremity deep venous thrombosis (DVT) is especially likely to recur or to develop complications such as pulmonary embolism and post-thrombotic syndrome. For this reason, practice guidelines now advocate early removal of iliofemoral clots if patients are functional, have a good life expectancy, are within 14 days of symptom onset, and are unlikely to develop bleeding complications. Options for clot removal include catheter-directed thrombolysis (CDT) or pharmacomechanical CDT, which combines catheterization with intervention to break up or aspirate the clot while infusing it with a thrombolytic drug, said the investigators (J. Vasc. Interv. Radiol. 2015 Mar. 27 [doi:10.1016/j.jvir.2015.01.036]).

The PEARL registry study prospectively followed patients who underwent PCDT for arterial or venous thrombosis with the AngioJet thrombectomy catheter system. Researchers analyzed data from 329 patients with severe lower-extremity DVT who were treated at 32 sites in the United States and Europe between 2007 and 2013. Two-thirds of the patients underwent Angiojet thrombectomy within 2 weeks of symptom onset, while 19% were treated within 15 to 30 days and 14% were treated for chronic lesions. A total of 57% of patients were men, and the average age at onset was 52 years. The cohort’s most prevalent risk factors for thrombosis included a history of DVT, preexisting caval filters, past or current tobacco use, and prior pulmonary embolism, the investigators reported.

Grade III (100%) clot removal was possible without needing to use CDT in 39% of patients. Most of these patients underwent PCDT alone (lasting a median of 2 hours), while the rest underwent rheolytic thrombectomy without a lytic agent (median, 1.4 hours). However, just over half of patients underwent PCDT and catheter-directed thrombolysis, lasting a median of 22 hours, and 9% underwent rheolytic thrombectomy with CDT (median, 41 hours). About three-quarters of patients had procedures lasting under 24 hours, and about one in three were done within 6 hours. Also, 86% of procedures required no more than two catheter laboratory sessions.

Three months after treatment, 94% of patients were free from rethrombosis, and 87% and 83% of the cohort remained so at 6 and 12 months, respectively, the researchers added. Even patients with chronic thrombi improved so much on the 12-item Short-Form Health Survey that their scores approximated population norms with a year of treatment, they said.

A total of nine patients (2.7%) had adverse events possibly related to treatment, including one case of acute renal failure, said the investigators. Clinicians should follow recommendations for hydration and limit run time to four minutes in a free-flowing vessel to prevent that outcome, they added.

Dr. Garcia and his associates reported being paid consultants for Boston Scientific, which makes the Angiojet thrombectomy catheter system and funded the study. Dr. Garcia also reported grant funds and consulting fees from BTG/EKOS and Cook. Four coauthors reported receiving consulting fees from Cordis, Cook, Medtronic, AstraZeneca, and Covidien.

More than 80% of patients with lower-extremity deep venous thrombosis who underwent endovascular treatment with the Angiojet rheolytic thrombectomy system were free of rethrombosis a year later, based on final results from the PEARL registry study.

Almost 4% of patients had bleeding events after treatment, but none of these events was tied to use of the Angiojet system, reported Dr. Mark Garcia of Mount Sinai Medical Center in New York and his associates.

Image provided courtesy of Boston Scientific. © 2015 Boston Scientific Corporation or its affiliates. All rights reserved.

“PEARL registry data demonstrate that rheolytic pharmacomechanical catheter-directed thrombolysis treatment of deep venous thrombosis is safe and effective, and can potentially reduce the need for concomitant catheter-directed thrombolysis and intensive care,” the researchers wrote.

The rates of venous thromboembolism are rising, and the number of affected adults is expected to double in the next 40 years as the population ages and experiences recurrent episodes. Lower-extremity deep venous thrombosis (DVT) is especially likely to recur or to develop complications such as pulmonary embolism and post-thrombotic syndrome. For this reason, practice guidelines now advocate early removal of iliofemoral clots if patients are functional, have a good life expectancy, are within 14 days of symptom onset, and are unlikely to develop bleeding complications. Options for clot removal include catheter-directed thrombolysis (CDT) or pharmacomechanical CDT, which combines catheterization with intervention to break up or aspirate the clot while infusing it with a thrombolytic drug, said the investigators (J. Vasc. Interv. Radiol. 2015 Mar. 27 [doi:10.1016/j.jvir.2015.01.036]).

The PEARL registry study prospectively followed patients who underwent PCDT for arterial or venous thrombosis with the AngioJet thrombectomy catheter system. Researchers analyzed data from 329 patients with severe lower-extremity DVT who were treated at 32 sites in the United States and Europe between 2007 and 2013. Two-thirds of the patients underwent Angiojet thrombectomy within 2 weeks of symptom onset, while 19% were treated within 15 to 30 days and 14% were treated for chronic lesions. A total of 57% of patients were men, and the average age at onset was 52 years. The cohort’s most prevalent risk factors for thrombosis included a history of DVT, preexisting caval filters, past or current tobacco use, and prior pulmonary embolism, the investigators reported.

Grade III (100%) clot removal was possible without needing to use CDT in 39% of patients. Most of these patients underwent PCDT alone (lasting a median of 2 hours), while the rest underwent rheolytic thrombectomy without a lytic agent (median, 1.4 hours). However, just over half of patients underwent PCDT and catheter-directed thrombolysis, lasting a median of 22 hours, and 9% underwent rheolytic thrombectomy with CDT (median, 41 hours). About three-quarters of patients had procedures lasting under 24 hours, and about one in three were done within 6 hours. Also, 86% of procedures required no more than two catheter laboratory sessions.

Three months after treatment, 94% of patients were free from rethrombosis, and 87% and 83% of the cohort remained so at 6 and 12 months, respectively, the researchers added. Even patients with chronic thrombi improved so much on the 12-item Short-Form Health Survey that their scores approximated population norms with a year of treatment, they said.

A total of nine patients (2.7%) had adverse events possibly related to treatment, including one case of acute renal failure, said the investigators. Clinicians should follow recommendations for hydration and limit run time to four minutes in a free-flowing vessel to prevent that outcome, they added.

Dr. Garcia and his associates reported being paid consultants for Boston Scientific, which makes the Angiojet thrombectomy catheter system and funded the study. Dr. Garcia also reported grant funds and consulting fees from BTG/EKOS and Cook. Four coauthors reported receiving consulting fees from Cordis, Cook, Medtronic, AstraZeneca, and Covidien.

More than 80% of patients with lower-extremity deep venous thrombosis who underwent endovascular treatment with the Angiojet rheolytic thrombectomy system were free of rethrombosis a year later, based on final results from the PEARL registry study.

Almost 4% of patients had bleeding events after treatment, but none of these events was tied to use of the Angiojet system, reported Dr. Mark Garcia of Mount Sinai Medical Center in New York and his associates.

Image provided courtesy of Boston Scientific. © 2015 Boston Scientific Corporation or its affiliates. All rights reserved.

“PEARL registry data demonstrate that rheolytic pharmacomechanical catheter-directed thrombolysis treatment of deep venous thrombosis is safe and effective, and can potentially reduce the need for concomitant catheter-directed thrombolysis and intensive care,” the researchers wrote.

The rates of venous thromboembolism are rising, and the number of affected adults is expected to double in the next 40 years as the population ages and experiences recurrent episodes. Lower-extremity deep venous thrombosis (DVT) is especially likely to recur or to develop complications such as pulmonary embolism and post-thrombotic syndrome. For this reason, practice guidelines now advocate early removal of iliofemoral clots if patients are functional, have a good life expectancy, are within 14 days of symptom onset, and are unlikely to develop bleeding complications. Options for clot removal include catheter-directed thrombolysis (CDT) or pharmacomechanical CDT, which combines catheterization with intervention to break up or aspirate the clot while infusing it with a thrombolytic drug, said the investigators (J. Vasc. Interv. Radiol. 2015 Mar. 27 [doi:10.1016/j.jvir.2015.01.036]).

The PEARL registry study prospectively followed patients who underwent PCDT for arterial or venous thrombosis with the AngioJet thrombectomy catheter system. Researchers analyzed data from 329 patients with severe lower-extremity DVT who were treated at 32 sites in the United States and Europe between 2007 and 2013. Two-thirds of the patients underwent Angiojet thrombectomy within 2 weeks of symptom onset, while 19% were treated within 15 to 30 days and 14% were treated for chronic lesions. A total of 57% of patients were men, and the average age at onset was 52 years. The cohort’s most prevalent risk factors for thrombosis included a history of DVT, preexisting caval filters, past or current tobacco use, and prior pulmonary embolism, the investigators reported.

Grade III (100%) clot removal was possible without needing to use CDT in 39% of patients. Most of these patients underwent PCDT alone (lasting a median of 2 hours), while the rest underwent rheolytic thrombectomy without a lytic agent (median, 1.4 hours). However, just over half of patients underwent PCDT and catheter-directed thrombolysis, lasting a median of 22 hours, and 9% underwent rheolytic thrombectomy with CDT (median, 41 hours). About three-quarters of patients had procedures lasting under 24 hours, and about one in three were done within 6 hours. Also, 86% of procedures required no more than two catheter laboratory sessions.

Three months after treatment, 94% of patients were free from rethrombosis, and 87% and 83% of the cohort remained so at 6 and 12 months, respectively, the researchers added. Even patients with chronic thrombi improved so much on the 12-item Short-Form Health Survey that their scores approximated population norms with a year of treatment, they said.

A total of nine patients (2.7%) had adverse events possibly related to treatment, including one case of acute renal failure, said the investigators. Clinicians should follow recommendations for hydration and limit run time to four minutes in a free-flowing vessel to prevent that outcome, they added.

Dr. Garcia and his associates reported being paid consultants for Boston Scientific, which makes the Angiojet thrombectomy catheter system and funded the study. Dr. Garcia also reported grant funds and consulting fees from BTG/EKOS and Cook. Four coauthors reported receiving consulting fees from Cordis, Cook, Medtronic, AstraZeneca, and Covidien.

Ten percent of patients who presented with acute MI to 24 U.S. hospitals during a 3-year study had unrecognized diabetes, and only one-third of these cases were identified during the MI hospitalization, according to a report published online April 21 in Circulation: Cardiovascular Quality and Outcomes.

To determine the prevalence of underlying but undiagnosed diabetes among patients hospitalized with acute MI, investigators reviewed the records of 2,854 patients enrolled in an MI registry. They identified 287 patients (10.1%) whose records showed HbA_1c levels of 6.5% or higher on routine laboratory testing and/or elevated fasting glucose levels at admission or during the typically 48- to 72-hour hospitalization.

Treating physicians recognized only 101 of these cases of diabetes (35%), as evidenced by their provision of diabetes education, prescription of glucose-lowering medication at discharge, or diagnosis code documentation in the patients’ charts, said Dr. Suzanne V. Arnold of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., and her associates.

The routine use of HbA_1c testing varied dramatically from one medical center to another, with some hospitals screening fewer than 10% of acute MI patients and others screening up to 82%. Incorporating universal HbA_1c screening into standardized acute MI care would likely improve these rates, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 April 21 [doi:10.1161/circoutcomes.114.001452]).

Fully 20% of the patients with unrecognized diabetes had very high HbA_1c values, ranging as high as 12.3%. Few of them received glucose-lowering medications during the 6 months after hospital discharge. “These data highlight a continued need to screen acute MI patients with HbA_1c, to improve the rate of diabetes recognition during the hospitalization; this would not only guide initiation of glucose management interventions but also inform several key aspects of post-MI cardiovascular care,” such as the timing and type of revascularization procedures and the selection of ACE inhibitors, beta-blockers, aldosterone inhibitors, and antiplatelet agents, they added.

Ten percent of patients who presented with acute MI to 24 U.S. hospitals during a 3-year study had unrecognized diabetes, and only one-third of these cases were identified during the MI hospitalization, according to a report published online April 21 in Circulation: Cardiovascular Quality and Outcomes.

To determine the prevalence of underlying but undiagnosed diabetes among patients hospitalized with acute MI, investigators reviewed the records of 2,854 patients enrolled in an MI registry. They identified 287 patients (10.1%) whose records showed HbA_1c levels of 6.5% or higher on routine laboratory testing and/or elevated fasting glucose levels at admission or during the typically 48- to 72-hour hospitalization.

Treating physicians recognized only 101 of these cases of diabetes (35%), as evidenced by their provision of diabetes education, prescription of glucose-lowering medication at discharge, or diagnosis code documentation in the patients’ charts, said Dr. Suzanne V. Arnold of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., and her associates.

The routine use of HbA_1c testing varied dramatically from one medical center to another, with some hospitals screening fewer than 10% of acute MI patients and others screening up to 82%. Incorporating universal HbA_1c screening into standardized acute MI care would likely improve these rates, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 April 21 [doi:10.1161/circoutcomes.114.001452]).

Fully 20% of the patients with unrecognized diabetes had very high HbA_1c values, ranging as high as 12.3%. Few of them received glucose-lowering medications during the 6 months after hospital discharge. “These data highlight a continued need to screen acute MI patients with HbA_1c, to improve the rate of diabetes recognition during the hospitalization; this would not only guide initiation of glucose management interventions but also inform several key aspects of post-MI cardiovascular care,” such as the timing and type of revascularization procedures and the selection of ACE inhibitors, beta-blockers, aldosterone inhibitors, and antiplatelet agents, they added.

Ten percent of patients who presented with acute MI to 24 U.S. hospitals during a 3-year study had unrecognized diabetes, and only one-third of these cases were identified during the MI hospitalization, according to a report published online April 21 in Circulation: Cardiovascular Quality and Outcomes.

To determine the prevalence of underlying but undiagnosed diabetes among patients hospitalized with acute MI, investigators reviewed the records of 2,854 patients enrolled in an MI registry. They identified 287 patients (10.1%) whose records showed HbA_1c levels of 6.5% or higher on routine laboratory testing and/or elevated fasting glucose levels at admission or during the typically 48- to 72-hour hospitalization.

Treating physicians recognized only 101 of these cases of diabetes (35%), as evidenced by their provision of diabetes education, prescription of glucose-lowering medication at discharge, or diagnosis code documentation in the patients’ charts, said Dr. Suzanne V. Arnold of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., and her associates.

The routine use of HbA_1c testing varied dramatically from one medical center to another, with some hospitals screening fewer than 10% of acute MI patients and others screening up to 82%. Incorporating universal HbA_1c screening into standardized acute MI care would likely improve these rates, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 April 21 [doi:10.1161/circoutcomes.114.001452]).

Fully 20% of the patients with unrecognized diabetes had very high HbA_1c values, ranging as high as 12.3%. Few of them received glucose-lowering medications during the 6 months after hospital discharge. “These data highlight a continued need to screen acute MI patients with HbA_1c, to improve the rate of diabetes recognition during the hospitalization; this would not only guide initiation of glucose management interventions but also inform several key aspects of post-MI cardiovascular care,” such as the timing and type of revascularization procedures and the selection of ACE inhibitors, beta-blockers, aldosterone inhibitors, and antiplatelet agents, they added.

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).

Patients with pulmonary embolism considered as low risk can be treated successfully as outpatients, according to a research letter by Dr. Margaret Fang and her associates.

Of nearly 5,000 patients included in the study, 494 were discharged from emergency departments. The proportion of PE patients discharged increased from 5.6% in 2004 to 11.1% in 2010. Just under 19% of those discharged visited the ED within 30 days, and 7.9% were hospitalized. Eleven patients were diagnosed with hemorrhage within 30 days, and there were two deaths within 90 days.

“Although still representing relatively few patients with PE, the proportion of discharges from ED settings nearly doubled during the 7-year study. Shifting appropriate patients to outpatient treatment may have benefits in terms of improved quality of life, enhanced physical and social functioning, and reduced costs of medical care,” the investigators said.

Find the full study in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2015.0936).