Anticoagulation Hub

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

CHICAGO – Nonwhite ethnicity and limb infection at diagnosis predict vascular events in patients with thromboangiitis obliterans (TAO), and the latter also predicts amputation, which occurs within 10 years of diagnosis in nearly a third of patients, according to findings from a large retrospective French cohort study.

Shidlovski/gettyimages

After a mean follow-up of 5.7 years, 58.9% of 224 patients with TAO – also known as Buerger’s disease – experienced a vascular event, 21.4% experienced at least one amputation, and 1.3% died, Alexandre Le Joncour, MD, reported at the annual meeting of the American College of Rheumatology.

The 5- and 15-year vascular event-free survival rates were 45% and 28%, respectively, and the 10- and 15-year amputation-free survival rates were 74%, and 66%, respectively, said Dr. Le Joncour of Sorbonne University, Paris.

Of note, no significant difference was seen in the vascular event-free survival rates based on tobacco use levels (more than 22 pack-years vs. 22 or fewer pack-years; HR, 1.2), he said.

Patient characteristics and clinical factors found to independently predict vascular events included nonwhite ethnicity (hazard ratio, 2.35; P = .005) and limb infection at diagnosis (HR, 3.29; P = .045). Limb infection at diagnosis also independently predicted amputation (HR, 12.1; P less than .001), he said.

“But there was no significant [association with amputation] in patients who had claudication, critical ischemia, or ischemic ulcers/necrosis,” he noted, adding that a comparison of white and nonwhite patients showed that the groups were similar with respect to epidemiologic and cardiovascular factors, clinical symptom distribution, and rates of addiction to tobacco, alcohol, and illicit drugs.

It was also clear that patients who quit using tobacco had a significantly lower risk of amputation than did those who continued using tobacco (P = .001), he said, explaining that 43 of the 48 patients who experienced amputation were current smokers, and 5 were ex-smokers at the time of amputation.

Dr. Le Joncour and his colleagues included TAO patients diagnosed between 1967 and 2016 at a median age of 36 years at the time of first symptoms, with a median of 12 months from symptom onset until diagnosis. About 76% were men, and about 83% were white. Patients with diabetes, atherosclerosis, arterial emboli, connective tissue disease, and/or thrombophilia were excluded.

Vascular events in this study were defined as “an acute worsening of the disease course requiring treatment modifications,” and included critical ischemia (35% of cases), ulcers/necrosis (33%), claudication worsening (16%), deep vein thrombosis (3%), superficial phlebitis (7%), limb infection (4%), and “other” events (2%).

Major amputation was defined as “an amputation involving the tibio-tarsian articulation for lower limbs and the metacarpophalangeal articulation for upper limbs,” he explained.

The median time to amputation was 4 years, and patients who experienced amputation had a median age of 39 years. Half of the 48 patients who experienced amputation had one amputation, nearly a third had two amputations, and 19% had three amputations. About two-thirds had minor amputations and a third had major amputations.

The findings provide important prognostic information regarding TAO, Dr. Le Joncour said, noting that long-term data on outcomes in TAO patients have been lacking.

“We found specific characteristics that identified those at highest risk for subsequent vascular complications, and these factors are not only important predictors of vascular complications or relapse, but may also serve to adjust more aggressive management and close follow-up of these patients,” he concluded.

Dr. Le Joncour reported having no disclosures.

[email protected]

SOURCE: Le Joncour A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1885.

CHICAGO – Nonwhite ethnicity and limb infection at diagnosis predict vascular events in patients with thromboangiitis obliterans (TAO), and the latter also predicts amputation, which occurs within 10 years of diagnosis in nearly a third of patients, according to findings from a large retrospective French cohort study.

Shidlovski/gettyimages

After a mean follow-up of 5.7 years, 58.9% of 224 patients with TAO – also known as Buerger’s disease – experienced a vascular event, 21.4% experienced at least one amputation, and 1.3% died, Alexandre Le Joncour, MD, reported at the annual meeting of the American College of Rheumatology.

The 5- and 15-year vascular event-free survival rates were 45% and 28%, respectively, and the 10- and 15-year amputation-free survival rates were 74%, and 66%, respectively, said Dr. Le Joncour of Sorbonne University, Paris.

Of note, no significant difference was seen in the vascular event-free survival rates based on tobacco use levels (more than 22 pack-years vs. 22 or fewer pack-years; HR, 1.2), he said.

Patient characteristics and clinical factors found to independently predict vascular events included nonwhite ethnicity (hazard ratio, 2.35; P = .005) and limb infection at diagnosis (HR, 3.29; P = .045). Limb infection at diagnosis also independently predicted amputation (HR, 12.1; P less than .001), he said.

“But there was no significant [association with amputation] in patients who had claudication, critical ischemia, or ischemic ulcers/necrosis,” he noted, adding that a comparison of white and nonwhite patients showed that the groups were similar with respect to epidemiologic and cardiovascular factors, clinical symptom distribution, and rates of addiction to tobacco, alcohol, and illicit drugs.

It was also clear that patients who quit using tobacco had a significantly lower risk of amputation than did those who continued using tobacco (P = .001), he said, explaining that 43 of the 48 patients who experienced amputation were current smokers, and 5 were ex-smokers at the time of amputation.

Dr. Le Joncour and his colleagues included TAO patients diagnosed between 1967 and 2016 at a median age of 36 years at the time of first symptoms, with a median of 12 months from symptom onset until diagnosis. About 76% were men, and about 83% were white. Patients with diabetes, atherosclerosis, arterial emboli, connective tissue disease, and/or thrombophilia were excluded.

Vascular events in this study were defined as “an acute worsening of the disease course requiring treatment modifications,” and included critical ischemia (35% of cases), ulcers/necrosis (33%), claudication worsening (16%), deep vein thrombosis (3%), superficial phlebitis (7%), limb infection (4%), and “other” events (2%).

Major amputation was defined as “an amputation involving the tibio-tarsian articulation for lower limbs and the metacarpophalangeal articulation for upper limbs,” he explained.

The median time to amputation was 4 years, and patients who experienced amputation had a median age of 39 years. Half of the 48 patients who experienced amputation had one amputation, nearly a third had two amputations, and 19% had three amputations. About two-thirds had minor amputations and a third had major amputations.

The findings provide important prognostic information regarding TAO, Dr. Le Joncour said, noting that long-term data on outcomes in TAO patients have been lacking.

“We found specific characteristics that identified those at highest risk for subsequent vascular complications, and these factors are not only important predictors of vascular complications or relapse, but may also serve to adjust more aggressive management and close follow-up of these patients,” he concluded.

Dr. Le Joncour reported having no disclosures.

[email protected]

SOURCE: Le Joncour A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1885.

CHICAGO – Nonwhite ethnicity and limb infection at diagnosis predict vascular events in patients with thromboangiitis obliterans (TAO), and the latter also predicts amputation, which occurs within 10 years of diagnosis in nearly a third of patients, according to findings from a large retrospective French cohort study.

Shidlovski/gettyimages

After a mean follow-up of 5.7 years, 58.9% of 224 patients with TAO – also known as Buerger’s disease – experienced a vascular event, 21.4% experienced at least one amputation, and 1.3% died, Alexandre Le Joncour, MD, reported at the annual meeting of the American College of Rheumatology.

The 5- and 15-year vascular event-free survival rates were 45% and 28%, respectively, and the 10- and 15-year amputation-free survival rates were 74%, and 66%, respectively, said Dr. Le Joncour of Sorbonne University, Paris.

Of note, no significant difference was seen in the vascular event-free survival rates based on tobacco use levels (more than 22 pack-years vs. 22 or fewer pack-years; HR, 1.2), he said.

Patient characteristics and clinical factors found to independently predict vascular events included nonwhite ethnicity (hazard ratio, 2.35; P = .005) and limb infection at diagnosis (HR, 3.29; P = .045). Limb infection at diagnosis also independently predicted amputation (HR, 12.1; P less than .001), he said.

“But there was no significant [association with amputation] in patients who had claudication, critical ischemia, or ischemic ulcers/necrosis,” he noted, adding that a comparison of white and nonwhite patients showed that the groups were similar with respect to epidemiologic and cardiovascular factors, clinical symptom distribution, and rates of addiction to tobacco, alcohol, and illicit drugs.

It was also clear that patients who quit using tobacco had a significantly lower risk of amputation than did those who continued using tobacco (P = .001), he said, explaining that 43 of the 48 patients who experienced amputation were current smokers, and 5 were ex-smokers at the time of amputation.

Dr. Le Joncour and his colleagues included TAO patients diagnosed between 1967 and 2016 at a median age of 36 years at the time of first symptoms, with a median of 12 months from symptom onset until diagnosis. About 76% were men, and about 83% were white. Patients with diabetes, atherosclerosis, arterial emboli, connective tissue disease, and/or thrombophilia were excluded.

Vascular events in this study were defined as “an acute worsening of the disease course requiring treatment modifications,” and included critical ischemia (35% of cases), ulcers/necrosis (33%), claudication worsening (16%), deep vein thrombosis (3%), superficial phlebitis (7%), limb infection (4%), and “other” events (2%).

Major amputation was defined as “an amputation involving the tibio-tarsian articulation for lower limbs and the metacarpophalangeal articulation for upper limbs,” he explained.

The median time to amputation was 4 years, and patients who experienced amputation had a median age of 39 years. Half of the 48 patients who experienced amputation had one amputation, nearly a third had two amputations, and 19% had three amputations. About two-thirds had minor amputations and a third had major amputations.

The findings provide important prognostic information regarding TAO, Dr. Le Joncour said, noting that long-term data on outcomes in TAO patients have been lacking.

“We found specific characteristics that identified those at highest risk for subsequent vascular complications, and these factors are not only important predictors of vascular complications or relapse, but may also serve to adjust more aggressive management and close follow-up of these patients,” he concluded.

Dr. Le Joncour reported having no disclosures.

[email protected]

SOURCE: Le Joncour A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1885.

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.

“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”

The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).

“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.

“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.

CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.

The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.

The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.

The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.

Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”

These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.

“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.

Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.

[email protected]

SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.

MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.

“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”

The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).

“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.

“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.

CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.

The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.

The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.

The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.

Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”

These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.

“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.

Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.

[email protected]

SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.

MONTREAL – An extended time window for thrombolytic treatment of acute ischemic stroke patients using tissue plasminogen activator out to 9 hours from stroke onset was safe and effective using CT perfusion imaging and automated imaging processing software to select suitable patients in the EXTEND trial. This result matches the groundbreaking finding reported earlier in 2018 that used MRI to select patients for extended thrombolysis.

“To reproduce our results you need to set up CT perfusion” as well as the RAPID software for automated image processing to identify patients with a small infarct core and a large area of salvageable brain, said Henry Ma, MD, a stroke neurologist at Monash University, Melbourne, as he reported results from the trial at the World Stroke Congress. “EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging.”

The new finding, from a trial with 225 randomized stroke patients, was especially notable because, by showing the validity of CT imaging for patient selection, it makes applying the extended time window for thrombolytic therapy more feasible for U.S. and Canadian stroke centers where CT imaging is much more common than MRI. A report from European investigators published in August 2018 from the WAKE-UP trial showed that thrombolysis with tissue plasminogen activator (tPA) was safe and effective when administered to patients who woke up with an acute ischemic stroke that had occurred more than 4.5 hours before treatment, but this study exclusively used MRI for patient selection (N Engl J Med. 2018 Aug 16;379[7]:611-22).

“In North America, our systems are more equipped for using CT,” commented Ashfaq Shuaib, MD, a professor of medicine and neurologist at the University of Alberta, Edmonton. Based on the WAKE-UP results, “MR would be preferred, but what we’ve been doing [since the WAKE-UP report] is if we see a CT scan that’s good we go ahead” with thrombolysis.

“Biologically, it doesn’t matter whether you use MR or CT; they both index the same underlying pathology. We’ve been hesitant to go beyond the MR finding from WAKE-UP, where there were data, but the findings from EXTEND were right in line with the WAKE-UP results, and that’s all we need to be reassured” that CT perfusion imaging also works for patient selection, commented Jeffrey L. Saver, MD, professor of medicine and director of the Comprehensive Stroke Center at the University of California, Los Angeles.

CT perfusion imaging and automated image processing “worked to select stroke patients” for an extended time window for treatment with mechanical thrombectomy in the DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21) and DEFUSE 3 (N Engl J Med. 2018 Feb 22;378[8]:308-18) trials, a history that makes the new finding of successfully using CT imaging to select patients who qualify for extended use of thrombolysis “a convincing result,” Dr. Saver said in an interview. The new EXTEND findings “will have a major impact” on using an extended time window for thrombolysis in U.S. practice, he predicted.

The EXTEND trial (Int J Stroke. 2012 Jan 1;7[1]:74-80) ran at 22 sites in Australia, 11 sites in Taiwan, and 1 center in New Zealand. Recruitment of patients into the study stopped early, after enrolling 225 patients, in June 2018, when results from WAKE-UP came out.

The EXTEND investigators enrolled patients who were either 4.5-9 hours out from the onset of their stroke or patients with a wake-up stroke with an uncertain onset. Participating centers could use either CT perfusion or MRI to identify candidates for treatment, and all used the RAPID software for image processing to identify patients with a perfusion lesion of at least 10 mL and an ischemic core volume no greater than 70 mL. Dr. Ma did not report what percentage of patients underwent imaging with each of these methods, but hinted that clinicians had used CT for a majority of the cases. The study randomized patients to receive either 0.9 mg/kg tPA or placebo, and by the trial protocol none of the enrolled patients received treatment with mechanical thrombectomy.

The trial’s primary endpoint was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days after their stroke, which was achieved by 44% more patients in the tPA group relative to the placebo arm after adjustment for age and baseline stroke severity, a statistically significant difference. The results were also positive for several secondary endpoints, such as recanalization 24 hours after treatment, which occurred in 67% of patients treated with tPA and 37% of the control patients, a statistically significant 68% relative improvement with thrombolysis.

Mortality at 90 days was similar in the two arms – 9% among the placebo patients and 12% among those who received tPA. The rate of symptomatic intracranial hemorrhage 36 hours after treatment was significantly higher among patients treated with tPA at 6%, compared with 1% in the placebo group, but the magnitude of this adverse effect was consistent with rates of intracranial hemorrhages previously reported in other studies of thrombolytic treatment for acute ischemic stroke, Dr. Ma said. The small number of increased intracranial hemorrhages “was not associated with increased mortality, and did not negate the positive result of an improved rate of excellent functional outcomes.”

These findings will likely spur further adoption of imaging processing software of the type used in EXTEND by U.S. stroke centers, Dr. Saver predicted.

“More and more centers have been getting this [software], and now they have two reasons to have it: to identify patients for an extended window for mechanical thrombectomy and to identify patients for an extended window for thrombolysis. It is a compelling case to have the imaging software as widely disseminated as possible. Centers that want to do the best for patients should have this imaging-processing software,” Dr. Saver said.

Dr. Ma and Dr. Shuaib reported no disclosures. Dr. Saver has received research funding and personal fees from Medtronic-Abbott and Neuravia.

[email protected]

SOURCE: Ma H et al. Int J. Stroke. 2018 Oct;13(2S):235, Abstract 1014.

MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.

Mitchel L. Zoler/MDedge News

Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.

The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.

These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.

First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.

“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”

The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.

GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.

GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.

[email protected]

MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.

Mitchel L. Zoler/MDedge News

Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.

The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.

These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.

First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.

“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”

The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.

GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.

GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.

[email protected]

MUNICH – Treatment of real-world patients newly diagnosed with atrial fibrillation using a direct oral anticoagulant led to benefits that tracked the advantages previously seen in randomized, controlled trials of these drugs, based on findings from more than 26,000 patients enrolled in a global registry.

Mitchel L. Zoler/MDedge News

Atrial fibrillation patients enrolled in the GARFIELD-AF(Global Anticoagulant Registry in the Field) study who started treatment with a direct oral anticoagulant (DOAC) had a 19% relative risk reduction in all-cause mortality during 2 years of follow-up, compared with patients on an oral vitamin K antagonist (VKA) regimen (such as warfarin), a statistically significant difference after adjustment for 30 demographic, clinical, and registry variables, A. John Camm, MD, said at the annual congress of the European Society of Cardiology. The analysis also showed trends toward lower rates of stroke or systemic thrombosis as well as major bleeding events when patients received a DOAC, compared with those on VKA, but these differences were not statistically significant, reported Dr. Camm, a professor of clinical cardiology at St. George’s University of London.

The analyses run by Dr. Camm and his associates also confirmed the superiority of oral anticoagulation. There was an adjusted 17% relative risk reduction in all-cause mortality during 2-year follow-up in patients on any form of oral anticoagulation, compared with patients who did not receive anticoagulation, a statistically significant difference. The comparison of patients on any oral anticoagulant with those not on treatment also showed a significant lowering of stroke or systemic embolism, as well as a 36% relative increase in the risk for a major bleeding episode that was close to statistical significance.

These findings in a registry of patients undergoing routine care “suggest that the effectiveness of oral anticoagulants in randomized clinical trials can be translated to the broad cross section of patients treated in everyday practice,” Dr. Camm said. However, he highlighted two important qualifications to the findings.

First, the analysis focused on the type of anticoagulation patients received at the time they entered the GARFIELD-AF registry and did not account for possible changes in treatment after that. Second, the analysis did not adjust for additional potential confounding variables, which Dr. Camm was certain existed and affected the findings.

“I’m concerned that a confounder we have not been able to account for is the quality of medical care that patients received,” he noted. “The substantial reduction in mortality [using a DOAC, compared with a VKA] is not simply due to reductions in stroke or major bleeding. We must look at other explanations, such as differences in quality of care and access to care.”

The analyses have also not yet looked at outcomes based on the specific DOAC a patient received – apixaban, dabigatran, edoxaban, or rivaroxaban – something that Dr. Camm said is in the works.

GARFIELD-AF enrolled nearly 35,000 patients with newly diagnosed atrial fibrillation and at least one stroke risk factor in 35 countries from April 2013 to September 2016. The analysis winnowed this down to 26,742 patients who also had a CHA2DS2-VASc score of at least 2 (which identifies patients with a high thrombotic risk) and had complete enrollment and follow-up data.

GARFIELD-AF was funded in part by Bayer. Dr. Camm reported being an adviser to Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/Bristol-Myers Squibb.

[email protected]

Anticoagulation thresholds based on CHA₂DS₂-VASc risk score varied from population to population, researchers reported in the Annals of Internal Medicine.

After accounting for differing rates of stroke in published studies, the benefit of warfarin anticoagulation varied nearly fourfold, said Sachin J. Shah, MD, of the University of California San Francisco and his associates. They called for guidelines that “better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation.”

Oral anticoagulation markedly reduces risk of ischemic stroke in patients with atrial fibrillation but increases the risk of major bleeding, including intracranial hemorrhage, which often is fatal. Therefore, when deciding whether to recommend oral anticoagulation, physicians must estimate clinical net benefit by quantifying the difference between reduction in stroke risk and increase in major bleeding risk, weighted by the severity of each outcome.

Guidelines on nonvalvular atrial fibrillation from the European Society of Cardiology and joint guidelines from the American Heart Association, American College of Cardiology, and Heart Rhythm Society (AHA/ACC/HRS) recommend oral anticoagulation when CHA₂DS₂-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) risk score is 2 or greater. These guidelines implicitly assume that a particular CHA₂DS₂-VASc score denotes the same amount of risk across populations, even though a recent meta-analysis found otherwise, as the researchers noted.

To further test this assumption, they applied an existing Markov model to data from more than 33,000 members of the ATRIA-CVRN cohort. All patients had nonvalvular atrial fibrillation, were members of Kaiser Permanente Northern California, and were diagnosed during 1996-1997. About 81% had a CHA₂DS₂-VASc score of at least 2. For each patient, the researchers produced four estimates of the net clinical benefit of oral anticoagulation based on ischemic stroke rates from ATRIA, the Swedish AF cohort study, the SPORTIF study, and the Danish National Patient Registry.

Optimal anticoagulation thresholds were a CHA₂DS₂-VASc score of 3 or more using stroke rates from ATRIA, 2 or more based on Swedish AF rates, 1 or more based on SPORTIF rates, and 0 or more using rates from the Danish National Patient Registry. Oral anticoagulation thresholds were lower but still varied widely after accounting for the lower rates of intracranial hemorrhage associated with non–vitamin K antagonist therapy.

Therefore, current guidelines based on CHA₂DS₂-VASc score may need revising “in favor of more accurate, individualized assessments of risk for both ischemic stroke and major bleeding,” the investigators wrote. “Until such time, guidelines should better reflect the uncertainty of the current approach in which a patient’s CHA₂DS₂-VASc score is used as the primary basis for recommending oral anticoagulation.”

The study had no primary funding source. Dr. Shah reported having no conflicts of interest. Three coinvestigators disclosed research support from relevant pharmaceutical or device companies.

SOURCE: Shah SJ et al. Ann Intern Med. 2018 Sep 25. doi: 10.7326/M17-2762  

Anticoagulation thresholds based on CHA₂DS₂-VASc risk score varied from population to population, researchers reported in the Annals of Internal Medicine.

After accounting for differing rates of stroke in published studies, the benefit of warfarin anticoagulation varied nearly fourfold, said Sachin J. Shah, MD, of the University of California San Francisco and his associates. They called for guidelines that “better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation.”

Oral anticoagulation markedly reduces risk of ischemic stroke in patients with atrial fibrillation but increases the risk of major bleeding, including intracranial hemorrhage, which often is fatal. Therefore, when deciding whether to recommend oral anticoagulation, physicians must estimate clinical net benefit by quantifying the difference between reduction in stroke risk and increase in major bleeding risk, weighted by the severity of each outcome.

Guidelines on nonvalvular atrial fibrillation from the European Society of Cardiology and joint guidelines from the American Heart Association, American College of Cardiology, and Heart Rhythm Society (AHA/ACC/HRS) recommend oral anticoagulation when CHA₂DS₂-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) risk score is 2 or greater. These guidelines implicitly assume that a particular CHA₂DS₂-VASc score denotes the same amount of risk across populations, even though a recent meta-analysis found otherwise, as the researchers noted.

To further test this assumption, they applied an existing Markov model to data from more than 33,000 members of the ATRIA-CVRN cohort. All patients had nonvalvular atrial fibrillation, were members of Kaiser Permanente Northern California, and were diagnosed during 1996-1997. About 81% had a CHA₂DS₂-VASc score of at least 2. For each patient, the researchers produced four estimates of the net clinical benefit of oral anticoagulation based on ischemic stroke rates from ATRIA, the Swedish AF cohort study, the SPORTIF study, and the Danish National Patient Registry.

Optimal anticoagulation thresholds were a CHA₂DS₂-VASc score of 3 or more using stroke rates from ATRIA, 2 or more based on Swedish AF rates, 1 or more based on SPORTIF rates, and 0 or more using rates from the Danish National Patient Registry. Oral anticoagulation thresholds were lower but still varied widely after accounting for the lower rates of intracranial hemorrhage associated with non–vitamin K antagonist therapy.

Therefore, current guidelines based on CHA₂DS₂-VASc score may need revising “in favor of more accurate, individualized assessments of risk for both ischemic stroke and major bleeding,” the investigators wrote. “Until such time, guidelines should better reflect the uncertainty of the current approach in which a patient’s CHA₂DS₂-VASc score is used as the primary basis for recommending oral anticoagulation.”

The study had no primary funding source. Dr. Shah reported having no conflicts of interest. Three coinvestigators disclosed research support from relevant pharmaceutical or device companies.

SOURCE: Shah SJ et al. Ann Intern Med. 2018 Sep 25. doi: 10.7326/M17-2762  

Anticoagulation thresholds based on CHA₂DS₂-VASc risk score varied from population to population, researchers reported in the Annals of Internal Medicine.

After accounting for differing rates of stroke in published studies, the benefit of warfarin anticoagulation varied nearly fourfold, said Sachin J. Shah, MD, of the University of California San Francisco and his associates. They called for guidelines that “better reflect the uncertainty in current thresholds of stroke risk score for recommending anticoagulation.”

Oral anticoagulation markedly reduces risk of ischemic stroke in patients with atrial fibrillation but increases the risk of major bleeding, including intracranial hemorrhage, which often is fatal. Therefore, when deciding whether to recommend oral anticoagulation, physicians must estimate clinical net benefit by quantifying the difference between reduction in stroke risk and increase in major bleeding risk, weighted by the severity of each outcome.

Guidelines on nonvalvular atrial fibrillation from the European Society of Cardiology and joint guidelines from the American Heart Association, American College of Cardiology, and Heart Rhythm Society (AHA/ACC/HRS) recommend oral anticoagulation when CHA₂DS₂-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) risk score is 2 or greater. These guidelines implicitly assume that a particular CHA₂DS₂-VASc score denotes the same amount of risk across populations, even though a recent meta-analysis found otherwise, as the researchers noted.

To further test this assumption, they applied an existing Markov model to data from more than 33,000 members of the ATRIA-CVRN cohort. All patients had nonvalvular atrial fibrillation, were members of Kaiser Permanente Northern California, and were diagnosed during 1996-1997. About 81% had a CHA₂DS₂-VASc score of at least 2. For each patient, the researchers produced four estimates of the net clinical benefit of oral anticoagulation based on ischemic stroke rates from ATRIA, the Swedish AF cohort study, the SPORTIF study, and the Danish National Patient Registry.

Optimal anticoagulation thresholds were a CHA₂DS₂-VASc score of 3 or more using stroke rates from ATRIA, 2 or more based on Swedish AF rates, 1 or more based on SPORTIF rates, and 0 or more using rates from the Danish National Patient Registry. Oral anticoagulation thresholds were lower but still varied widely after accounting for the lower rates of intracranial hemorrhage associated with non–vitamin K antagonist therapy.

Therefore, current guidelines based on CHA₂DS₂-VASc score may need revising “in favor of more accurate, individualized assessments of risk for both ischemic stroke and major bleeding,” the investigators wrote. “Until such time, guidelines should better reflect the uncertainty of the current approach in which a patient’s CHA₂DS₂-VASc score is used as the primary basis for recommending oral anticoagulation.”

The study had no primary funding source. Dr. Shah reported having no conflicts of interest. Three coinvestigators disclosed research support from relevant pharmaceutical or device companies.

SOURCE: Shah SJ et al. Ann Intern Med. 2018 Sep 25. doi: 10.7326/M17-2762  

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

For patients with atrial fibrillation with at least one risk factor besides gender, oral anticoagulation is the optimal choice of antithrombotic therapy, experts said in a comprehensive, updated guideline.

©Thinkstock

The 113-page guideline, published in the journal CHEST^®, provides antithrombotic treatment recommendations for atrial fibrillation based on different levels of risk for stroke and in a variety of clinical presentations.

Altogether, the new guidelines highlight 60 key recommendations from the 12-person expert panel, chaired by Gregory Y.H. Lip, MD, of the Institute of Cardiovascular Sciences, University of Birmingham (England).

To develop the guidelines, the panel conducted a systematic literature review of relevant articles released since the 2012 publication of Thrombolytic Therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (9th Edition).

Since that time, “there have been substantial developments in atrial fibrillation thromboprophylaxis, whether with regard to risk assessment, antithrombotic drugs, or non-drug approaches,” panelists said in their report.

The panel graded the quality of the new evidence found in the literature review, and then undertook a consensus development process. Each recommendation and statement required at least 80% consensus to pass.

Their treatment recommendations in the report are focused on three topic areas: stroke and bleeding risk assessment, antithrombotic therapy in general, and antithrombotic therapy in special situations, such as acute coronary syndrome and stenting, chronic atrial flutter, pregnancy, and chronic kidney disease.

Stroke prevention is the main priority in a “holistic approach” to management of atrial fibrillation, the panelists said in the report.

“Many of the risk factors leading to incident AF are also risk factors for ischemic stroke, and the promotion of an integrated or holistic approach to AF management is needed, incorporating stroke prevention, addressing symptoms and risk factor management,” they said.

No antithrombotic therapy is needed for patients who have atrial fibrillation without valvular heart disease, the panelists concluded.

For patients with at least one nongender CHA2DS2-VASc stroke risk factor, oral anticoagulation is recommended over aspirin, aspirin and clopidogrel, or no therapy, they said.

In high-risk patients, including males with two or more CHA₂DS₂-VASc risk factors and females with three or more, novel oral anticoagulants are recommended over adjusted-dose warfarin, they added.

At each patient contact, patients with atrial fibrillation should receive bleeding risk assessment starting with potentially modifiable risk factors such as uncontrolled blood pressure or excessive alcohol intake, according to the expert panel.

High-risk patients, as indicated by a HAS-BLED score of 3 or greater, should have more frequent and regular follow-up, they said.

The expert panel report concludes with a discussion on practical and patient-centered issues.

“Patient education is essential to provide patients with sufficient information to enable them to make an informed decision about whether or not they wish to take oral anticoagulants, and if they do, which oral anticoagulant they would prefer,” Dr. Lip and his colleagues said in their report.

Dr. Lip disclosed a potential conflict of interest with Boehringer Ingelheim. Expert panel members reported disclosures related to Boston Scientific, Medtronic, St. Jude Medical, Biotronik, MSD, Novartis, Pfizer, Bayer, Servier, Gilead, Bristol-Myers Squibb, AstraZeneca, and others.

SOURCE: Lip GYH et al. CHEST. 2018 Aug 21. pii: S0012-3692(18)32244-X.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]