Venous Diseases

CHICAGO – A closer look at the landmark ATTRACT trial of pharmacomechanical catheter-directed thrombolysis for acute deep vein thrombosis (DVT) shows multiple benefits for the intervention versus standard anticoagulation alone in the subset of participants with iliofemoral DVT, Kush R. Desai, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

ATTRACT, a National Institutes of Health–sponsored, phase 3, multicenter, open-label, assessor-blinded study, was the first-ever randomized trial of pharmacomechanical catheter-directed thrombolysis (PCDT) for acute DVT.

The results caused a major stir because, despite a sound therapeutic rationale for the procedure, the incidence of chronic postthrombotic syndrome (PTS) at 24 months of follow-up was 47% in the PCDT plus anticoagulation group and 48% in controls on anticoagulation alone (N Engl J Med. 2017 Dec 7;377[23]:2240-52). Since then, that overall negative trial has been one of the hottest topics in DVT.

“This is the first thing your educated patients who come to the emergency department with DVT will ask about. It’s the first thing they’ll see when they go online and type in ‘thrombolysis DVT,’ ” noted Dr. Desai, an interventional radiologist at Northwestern University, Chicago.


But the trial has several major flaws, he cautioned. And contrary to popular opinion, ATTRACT is not the death knell for PCDT. Far from it.

“I don’t think the story stops with ATTRACT. This isn’t the end for PCDT in patients with iliofemoral DVT,” he asserted.

That’s in part because 301 of the 692 participants in ATTRACT had DVT of the femoropopliteal segment. That’s a population in which Dr. Desai and other interventionalists wouldn’t have anticipated seeing a benefit for PCDT, because their risk of PTS is so low.

“We know through historical data that patients with iliofemoral DVT are much more likely to develop PTS and to have recurrent DVT, so this is probably one of the major shortcomings of the trial,” he explained. “It’s through no fault of the trial investigators, because the study was planned years ago when we just didn’t know as much about PTS as we do now.

“The way I look at it is, I don’t practice in the way that ATTRACT was designed,” Dr. Desai said. “I don’t typically lyse or get referrals for lysis or thrombectomy in patients who have isolated femoropopliteal DVT. It has to involve at least the common femoral vein and frequently goes up to the iliac vein.”

The ATTRACT investigators’ recent subanalysis of the 391 participants with iliofemoral DVT showed that, although there was no difference between the two study arms in the occurrence of PTS through the first 24 months of follow-up, PCDT led to a 35% reduction in the incidence of moderate or severe PTS – by a margin of 18% versus 28% in controls.

Patients in the PCDT arm also experienced significantly greater improvement in venous disease-specific quality of life through 24 months, and a greater reduction in leg pain and swelling at 10 and 30 days (Circulation. 2018 Dec 4. doi: 10.1161/CIRCULATIONAHA.118.037425).

And moderate to severe PTS is a key outcome, Dr. Desai continued. Multiple studies have shown that patients with PTS have a worse quality of life than those with chronic lung disease, arthritis, or diabetes. Moreover, the 5%-10% of patients with symptomatic DVT who develop the most-severe form of PTS – characterized by severe pain, chronic ulcerations, stasis dermatitis, venous claudication, and intractable edema – have a quality of life comparable with patients with cancer or heart failure.

The 1.5% incidence of major bleeding within 10 days in the PCDT group was 200% higher than in controls, but none of it was life threatening.

“This is reassuring: Nobody had intracranial hemorrhage; nobody had a GUSTO 5 bleed,” Dr. Desai said.

Another limitation of the ATTRACT trial is that all but one of the devices utilized for PCDT were used off label. They weren’t designed for venous application. Several on-label rheolytic, rotational thrombectomy, or clot aspiration devices have been approved since enrollment in ATTRACT was closed. Future randomized trials will utilize on-label devices in patients with acute iliofemoral DVT to clarify the role of PCDT.

It’s noteworthy that nearly half of ATTRACT participants developed PTS within 24 months of their DVT despite being on optimal anticoagulation. It’s a finding that underscores the need for improved therapies. That was the impetus for development of first-generation catheter-directed thrombolysis utilizing a percutaneously inserted catheter to infuse a fibrinolytic drug directly to the thrombus to dissolve it rapidly.

But that form of catheter-directed thrombolysis has major disadvantages, Dr. Desai explained: It’s a multiday procedure requiring ICU-level care and prolonged exposure to powerful lytic agents.

“This is where things have changed with PCDT,” he said. “We can now, with on-label devices, accelerate the thrombolysis time, reduce lytic exposure, and I think also reduce the bleeding risk, although that hasn’t been shown in a trial yet. PCDT also reduces the necessity for ICU-level care and prolonged hospitalization.”

Dr. Desai no longer performs multiday lytic procedures. “In fact, with the introduction of the newer on-label devices, I haven’t done a multiday unilateral limb lytic procedure in a couple years. I think we’ve gotten to the point where we don’t need to do that anymore.”

Indeed, PCDT makes recanalization possible as a single-day, single-session procedure.

Dr. Desai views the recent ATTRACT subanalysis as hypothesis generating.

“Should PCDT be the first-line treatment in all proximal DVT patients? No it should not – and that’s not what I would have advocated even before ATTRACT came out,” he explained. “It’s sort of a salvage procedure for patients with iliofemoral DVT and moderate to severe symptoms. And there are a significant number of such patients.”

Current understanding of the pathophysiology of PTS is that a nondissolved thrombus at the valve leaflets becomes inflammatory, with resultant valvular dysfunction leading to venous reflux and venous hypertension. PCDT is consistent with the open-vein hypothesis, which posits that, by eliminating thrombus much faster than achievable via anticoagulation, valve integrity is maintained and PTS is prevented.

Dr. Desai reported receiving consulting fees from AngioDynamics, Boston Scientific, Cook Medical, and Spectranetics.

bjancin@mdedge.com

CHICAGO – A closer look at the landmark ATTRACT trial of pharmacomechanical catheter-directed thrombolysis for acute deep vein thrombosis (DVT) shows multiple benefits for the intervention versus standard anticoagulation alone in the subset of participants with iliofemoral DVT, Kush R. Desai, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

ATTRACT, a National Institutes of Health–sponsored, phase 3, multicenter, open-label, assessor-blinded study, was the first-ever randomized trial of pharmacomechanical catheter-directed thrombolysis (PCDT) for acute DVT.

The results caused a major stir because, despite a sound therapeutic rationale for the procedure, the incidence of chronic postthrombotic syndrome (PTS) at 24 months of follow-up was 47% in the PCDT plus anticoagulation group and 48% in controls on anticoagulation alone (N Engl J Med. 2017 Dec 7;377[23]:2240-52). Since then, that overall negative trial has been one of the hottest topics in DVT.

“This is the first thing your educated patients who come to the emergency department with DVT will ask about. It’s the first thing they’ll see when they go online and type in ‘thrombolysis DVT,’ ” noted Dr. Desai, an interventional radiologist at Northwestern University, Chicago.


But the trial has several major flaws, he cautioned. And contrary to popular opinion, ATTRACT is not the death knell for PCDT. Far from it.

“I don’t think the story stops with ATTRACT. This isn’t the end for PCDT in patients with iliofemoral DVT,” he asserted.

That’s in part because 301 of the 692 participants in ATTRACT had DVT of the femoropopliteal segment. That’s a population in which Dr. Desai and other interventionalists wouldn’t have anticipated seeing a benefit for PCDT, because their risk of PTS is so low.

“We know through historical data that patients with iliofemoral DVT are much more likely to develop PTS and to have recurrent DVT, so this is probably one of the major shortcomings of the trial,” he explained. “It’s through no fault of the trial investigators, because the study was planned years ago when we just didn’t know as much about PTS as we do now.

“The way I look at it is, I don’t practice in the way that ATTRACT was designed,” Dr. Desai said. “I don’t typically lyse or get referrals for lysis or thrombectomy in patients who have isolated femoropopliteal DVT. It has to involve at least the common femoral vein and frequently goes up to the iliac vein.”

The ATTRACT investigators’ recent subanalysis of the 391 participants with iliofemoral DVT showed that, although there was no difference between the two study arms in the occurrence of PTS through the first 24 months of follow-up, PCDT led to a 35% reduction in the incidence of moderate or severe PTS – by a margin of 18% versus 28% in controls.

Patients in the PCDT arm also experienced significantly greater improvement in venous disease-specific quality of life through 24 months, and a greater reduction in leg pain and swelling at 10 and 30 days (Circulation. 2018 Dec 4. doi: 10.1161/CIRCULATIONAHA.118.037425).

And moderate to severe PTS is a key outcome, Dr. Desai continued. Multiple studies have shown that patients with PTS have a worse quality of life than those with chronic lung disease, arthritis, or diabetes. Moreover, the 5%-10% of patients with symptomatic DVT who develop the most-severe form of PTS – characterized by severe pain, chronic ulcerations, stasis dermatitis, venous claudication, and intractable edema – have a quality of life comparable with patients with cancer or heart failure.

The 1.5% incidence of major bleeding within 10 days in the PCDT group was 200% higher than in controls, but none of it was life threatening.

“This is reassuring: Nobody had intracranial hemorrhage; nobody had a GUSTO 5 bleed,” Dr. Desai said.

Another limitation of the ATTRACT trial is that all but one of the devices utilized for PCDT were used off label. They weren’t designed for venous application. Several on-label rheolytic, rotational thrombectomy, or clot aspiration devices have been approved since enrollment in ATTRACT was closed. Future randomized trials will utilize on-label devices in patients with acute iliofemoral DVT to clarify the role of PCDT.

It’s noteworthy that nearly half of ATTRACT participants developed PTS within 24 months of their DVT despite being on optimal anticoagulation. It’s a finding that underscores the need for improved therapies. That was the impetus for development of first-generation catheter-directed thrombolysis utilizing a percutaneously inserted catheter to infuse a fibrinolytic drug directly to the thrombus to dissolve it rapidly.

But that form of catheter-directed thrombolysis has major disadvantages, Dr. Desai explained: It’s a multiday procedure requiring ICU-level care and prolonged exposure to powerful lytic agents.

“This is where things have changed with PCDT,” he said. “We can now, with on-label devices, accelerate the thrombolysis time, reduce lytic exposure, and I think also reduce the bleeding risk, although that hasn’t been shown in a trial yet. PCDT also reduces the necessity for ICU-level care and prolonged hospitalization.”

Dr. Desai no longer performs multiday lytic procedures. “In fact, with the introduction of the newer on-label devices, I haven’t done a multiday unilateral limb lytic procedure in a couple years. I think we’ve gotten to the point where we don’t need to do that anymore.”

Indeed, PCDT makes recanalization possible as a single-day, single-session procedure.

Dr. Desai views the recent ATTRACT subanalysis as hypothesis generating.

“Should PCDT be the first-line treatment in all proximal DVT patients? No it should not – and that’s not what I would have advocated even before ATTRACT came out,” he explained. “It’s sort of a salvage procedure for patients with iliofemoral DVT and moderate to severe symptoms. And there are a significant number of such patients.”

Current understanding of the pathophysiology of PTS is that a nondissolved thrombus at the valve leaflets becomes inflammatory, with resultant valvular dysfunction leading to venous reflux and venous hypertension. PCDT is consistent with the open-vein hypothesis, which posits that, by eliminating thrombus much faster than achievable via anticoagulation, valve integrity is maintained and PTS is prevented.

Dr. Desai reported receiving consulting fees from AngioDynamics, Boston Scientific, Cook Medical, and Spectranetics.

bjancin@mdedge.com

CHICAGO – A closer look at the landmark ATTRACT trial of pharmacomechanical catheter-directed thrombolysis for acute deep vein thrombosis (DVT) shows multiple benefits for the intervention versus standard anticoagulation alone in the subset of participants with iliofemoral DVT, Kush R. Desai, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

ATTRACT, a National Institutes of Health–sponsored, phase 3, multicenter, open-label, assessor-blinded study, was the first-ever randomized trial of pharmacomechanical catheter-directed thrombolysis (PCDT) for acute DVT.

The results caused a major stir because, despite a sound therapeutic rationale for the procedure, the incidence of chronic postthrombotic syndrome (PTS) at 24 months of follow-up was 47% in the PCDT plus anticoagulation group and 48% in controls on anticoagulation alone (N Engl J Med. 2017 Dec 7;377[23]:2240-52). Since then, that overall negative trial has been one of the hottest topics in DVT.

“This is the first thing your educated patients who come to the emergency department with DVT will ask about. It’s the first thing they’ll see when they go online and type in ‘thrombolysis DVT,’ ” noted Dr. Desai, an interventional radiologist at Northwestern University, Chicago.


But the trial has several major flaws, he cautioned. And contrary to popular opinion, ATTRACT is not the death knell for PCDT. Far from it.

“I don’t think the story stops with ATTRACT. This isn’t the end for PCDT in patients with iliofemoral DVT,” he asserted.

That’s in part because 301 of the 692 participants in ATTRACT had DVT of the femoropopliteal segment. That’s a population in which Dr. Desai and other interventionalists wouldn’t have anticipated seeing a benefit for PCDT, because their risk of PTS is so low.

“We know through historical data that patients with iliofemoral DVT are much more likely to develop PTS and to have recurrent DVT, so this is probably one of the major shortcomings of the trial,” he explained. “It’s through no fault of the trial investigators, because the study was planned years ago when we just didn’t know as much about PTS as we do now.

“The way I look at it is, I don’t practice in the way that ATTRACT was designed,” Dr. Desai said. “I don’t typically lyse or get referrals for lysis or thrombectomy in patients who have isolated femoropopliteal DVT. It has to involve at least the common femoral vein and frequently goes up to the iliac vein.”

The ATTRACT investigators’ recent subanalysis of the 391 participants with iliofemoral DVT showed that, although there was no difference between the two study arms in the occurrence of PTS through the first 24 months of follow-up, PCDT led to a 35% reduction in the incidence of moderate or severe PTS – by a margin of 18% versus 28% in controls.

Patients in the PCDT arm also experienced significantly greater improvement in venous disease-specific quality of life through 24 months, and a greater reduction in leg pain and swelling at 10 and 30 days (Circulation. 2018 Dec 4. doi: 10.1161/CIRCULATIONAHA.118.037425).

And moderate to severe PTS is a key outcome, Dr. Desai continued. Multiple studies have shown that patients with PTS have a worse quality of life than those with chronic lung disease, arthritis, or diabetes. Moreover, the 5%-10% of patients with symptomatic DVT who develop the most-severe form of PTS – characterized by severe pain, chronic ulcerations, stasis dermatitis, venous claudication, and intractable edema – have a quality of life comparable with patients with cancer or heart failure.

The 1.5% incidence of major bleeding within 10 days in the PCDT group was 200% higher than in controls, but none of it was life threatening.

“This is reassuring: Nobody had intracranial hemorrhage; nobody had a GUSTO 5 bleed,” Dr. Desai said.

Another limitation of the ATTRACT trial is that all but one of the devices utilized for PCDT were used off label. They weren’t designed for venous application. Several on-label rheolytic, rotational thrombectomy, or clot aspiration devices have been approved since enrollment in ATTRACT was closed. Future randomized trials will utilize on-label devices in patients with acute iliofemoral DVT to clarify the role of PCDT.

It’s noteworthy that nearly half of ATTRACT participants developed PTS within 24 months of their DVT despite being on optimal anticoagulation. It’s a finding that underscores the need for improved therapies. That was the impetus for development of first-generation catheter-directed thrombolysis utilizing a percutaneously inserted catheter to infuse a fibrinolytic drug directly to the thrombus to dissolve it rapidly.

But that form of catheter-directed thrombolysis has major disadvantages, Dr. Desai explained: It’s a multiday procedure requiring ICU-level care and prolonged exposure to powerful lytic agents.

“This is where things have changed with PCDT,” he said. “We can now, with on-label devices, accelerate the thrombolysis time, reduce lytic exposure, and I think also reduce the bleeding risk, although that hasn’t been shown in a trial yet. PCDT also reduces the necessity for ICU-level care and prolonged hospitalization.”

Dr. Desai no longer performs multiday lytic procedures. “In fact, with the introduction of the newer on-label devices, I haven’t done a multiday unilateral limb lytic procedure in a couple years. I think we’ve gotten to the point where we don’t need to do that anymore.”

Indeed, PCDT makes recanalization possible as a single-day, single-session procedure.

Dr. Desai views the recent ATTRACT subanalysis as hypothesis generating.

“Should PCDT be the first-line treatment in all proximal DVT patients? No it should not – and that’s not what I would have advocated even before ATTRACT came out,” he explained. “It’s sort of a salvage procedure for patients with iliofemoral DVT and moderate to severe symptoms. And there are a significant number of such patients.”

Current understanding of the pathophysiology of PTS is that a nondissolved thrombus at the valve leaflets becomes inflammatory, with resultant valvular dysfunction leading to venous reflux and venous hypertension. PCDT is consistent with the open-vein hypothesis, which posits that, by eliminating thrombus much faster than achievable via anticoagulation, valve integrity is maintained and PTS is prevented.

Dr. Desai reported receiving consulting fees from AngioDynamics, Boston Scientific, Cook Medical, and Spectranetics.

bjancin@mdedge.com

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

IgA vasculitis, also called Henoch-Schönlein purpura, increases risks for hypertension and chronic kidney disease (CKD), according to a retrospective study of more than 13,000 patients with IgAV.

In patients with adult-onset IgA vasculitis (IgAV), mortality risk is also increased, reported first author Alexander Tracy and his colleagues at the University of Birmingham (England).

“Long-term health outcomes of adult-onset IgAV are not well characterized,” the investigators wrote in Annals of Rheumatic Disease. “Most evidence regarding complications of IgAV in adults derives from case reports and case series; there is need for controlled epidemiological studies to address this question.”

The retrospective study compared 2,828 patients with adult-onset IgAV and 10,405 patients with childhood-onset IgAV against sex- and age-matched controls. Patients diagnosed at age 16 years or older were classified as having adult-onset disease. The investigators drew their data from The Health Improvement Network database, which includes 3.6 million active patients from more than 675 general practices in the United Kingdom. Patients in the present study were diagnosed with IgAV between 2005 and 2016. After diagnosis, participant follow-up continued until any of the following occurred: outcome event, patient left practice, death, the practice stopped contributing data, or the study ended. Primary outcomes for adult-onset patients were venous thromboembolism (VTE), ischemic heart disease, hypertension, stage 3-5 CKD, stroke/transient ischemic attack, and all-cause mortality. Primary outcomes for patients with childhood-onset disease were limited to CKD, hypertension, and VTE.

The incidence of childhood-onset IgAV was 27.22 per 100,000 person-years, whereas adult-onset disease was much less common at 2.20 per 100,000 person-years. Mean age at onset of childhood IgAV was 6.68 years. The adult-onset group had a mean age at diagnosis of 38.1 years.


Compared with controls, all patients with IgAV, regardless of onset age, had increased risks of hypertension (adult-onset adjusted hazard ratio, 1.42; P less than .001; childhood-onset aHR, 1.52; P less than .001) and CKD (adult-onset aHR, 1.54; P less than .001; childhood-onset aHR, 1.89; P = .01). Patients with adult-onset IgAV showed increased risk of death, compared with controls (aHR, 1.27; P = .006). No associations were found between IgAV and stroke/transient ischemic attack, VTE, or ischemic heart disease.

“These findings emphasize the importance of blood pressure and renal function monitoring in patients with IgAV,” the investigators concluded. “Our data also suggest that IgAV should not be considered a ‘single-hit’ disease, but that clinicians should monitor for long-term sequelae. Further research is required to clarify the cause of hypertension in patients with IgAV, and to investigate whether such patients suffer from additional long-term sequelae than that are currently unrecognized.”

The investigators reported no funding sources or conflicts or interest.

SOURCE: Tracy A et al. Ann Rheum Dis. 2018 Nov 28. doi: 10.1136/annrheumdis-2018-214142.

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.

sworcester@mdedge.com

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.

sworcester@mdedge.com

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.

sworcester@mdedge.com

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

NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.

In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).

These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.

Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.

If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.

NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.

In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).

These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.

Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.

If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.

NEW YORK – Guidelines for the management of leg ulcerations will be changed to accommodate the results of the Early Venous Reflux Ablation trial, according to this video interview with the senior author, Alun H Davies, DSc, professor of vascular surgery, Imperial College, London.

In this video interview, conducted at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation, Dr. Davies recaps the major results of the study, which associated immediate endovascular ablation (early intervention) with significantly faster healing than did compression therapy with ablation, considered only after 6 months (delayed intervention).

These data have been published (N Engl J Med 2018 May 31;378:2105-14), but Dr. Davies focused in this interview on the cost efficacy of early intervention with endovascular ablation. In the United Kingdom, where the study was conducted, the data support the cost efficacy, but Dr. Davies predicted even greater savings in the United States because of the expense of frequent wound care visits.

Based on data from a randomized trial, he expects guidelines, including those in the United States, to be revised to list early endovascular ablation as a 1b or 1A recommendation, thereby establishing this intervention as a standard.

If follow-up after 3 years confirms a lower rate of recurrence, an advantage previously shown for open surgery relative to compression healing, the case for early endovascular intervention will be even stronger, according to Dr. Davies.

NEW YORK – Registry data can be used to craft guidance for determining the appropriateness of procedures at vein centers, based on data presented by Thomas W. Wakefield, MD at the 2018 Veith Symposium.

The Vascular Quality Initiative Varicose Vein Registry (VQI-VVR), initiated in 2014 by the Society for Vascular Surgery in conjunction with the American Venous Forum, captures procedures that are performed in vein centers, office-based practices, and ambulatory or inpatient settings. The VVR looks at ablation and phlebectomy techniques and captures data including patient demographics, history, procedure data, plus early and late office-based and patient-reported follow-up in order to benchmark and improve outcomes and develop best practices and to help meet vein center certification requirements. The VVR includes 39 centers and more than 23,000 procedures.

Dr. Wakefield, who heads the VVR, used this registry as a means to illustrate how VQIs could be used to establish whether “the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin that the procedure is worth doing.” This can be considered to be “appropriateness, which is part of ethical treatment.” Dr. Wakefield is the Stanley Professor of Vascular Surgery at the University of Michigan and section head, vascular surgery, University of Michigan Cardiovascular Center, Ann Arbor.

Data from the VQI registry (of which the VVR is a component) are now being used to generate appropriateness reports, said Dr. Wakefield.

The VQI represents a large comprehensive database of long-term data to define appropriate care. In addition, the VQI infrastructure is already geared to producing these reports both at a center and at a surgeon level. One disadvantage of the VVR registry, however, is low participation – only the 39 centers – and that it doesn’t capture cosmetic procedures and lesser (C1) disease. Further, it’s “likely the VQI participants are the ‘good actors,’ ” he added.

Targets for appropriateness include the proportion of patients undergoing ablation C2 or C4 disease or greater, the mean number of ablations per patient, the mean number of ablations per limb, and the proportion of perforated ablations for greater than C4 disease. Plotting out the data for these procedures at the center level can be assessed against current thinking on best practices in the various areas. For example, “the mean number of ablations per patient has been suggested at 1.8 to be about the right number,” and he used the graph of the center performance in this area to show that most of the centers were below this objective.

In an even more appropriate example of how this kind of data could be used to determine appropriateness, Dr. Wakefield described how perforated ablations should be performed for greater than C4 disease, but not for C2 disease. He described how, according to the actual data in the registry, there have been 870 total perforated treatments recorded, 38% for C2 disease, and of these 332 procedures, almost half of these were performed at one center only, with two other centers reporting 30 such procedures. “So clearly there are three centers that are doing perforated ablations for patients that are outside the guidelines,” Dr. Wakefield pointed out.

In future, payer demand is likely to demand that each treating physician provide evidence of the appropriateness of procedures performed, as well as appropriate patient selection and adherence to best practices, and good outcomes, which is part of what a society-based registry such as the VVR can provide.

“I believe the VQI-VVR is well-positioned to meet these needs. And if we ask the question ‘can VQI be used as a benchmark for setting ethical standards,’ I think it can certainly be used to help set appropriate standards, and since appropriateness is one part of ethical standards, I believe it has a role,” he concluded.

Dr. Wakefield reported that he had no disclosures.

mlesney@mdedge.com

NEW YORK – Registry data can be used to craft guidance for determining the appropriateness of procedures at vein centers, based on data presented by Thomas W. Wakefield, MD at the 2018 Veith Symposium.

The Vascular Quality Initiative Varicose Vein Registry (VQI-VVR), initiated in 2014 by the Society for Vascular Surgery in conjunction with the American Venous Forum, captures procedures that are performed in vein centers, office-based practices, and ambulatory or inpatient settings. The VVR looks at ablation and phlebectomy techniques and captures data including patient demographics, history, procedure data, plus early and late office-based and patient-reported follow-up in order to benchmark and improve outcomes and develop best practices and to help meet vein center certification requirements. The VVR includes 39 centers and more than 23,000 procedures.

Dr. Wakefield, who heads the VVR, used this registry as a means to illustrate how VQIs could be used to establish whether “the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin that the procedure is worth doing.” This can be considered to be “appropriateness, which is part of ethical treatment.” Dr. Wakefield is the Stanley Professor of Vascular Surgery at the University of Michigan and section head, vascular surgery, University of Michigan Cardiovascular Center, Ann Arbor.

Data from the VQI registry (of which the VVR is a component) are now being used to generate appropriateness reports, said Dr. Wakefield.

The VQI represents a large comprehensive database of long-term data to define appropriate care. In addition, the VQI infrastructure is already geared to producing these reports both at a center and at a surgeon level. One disadvantage of the VVR registry, however, is low participation – only the 39 centers – and that it doesn’t capture cosmetic procedures and lesser (C1) disease. Further, it’s “likely the VQI participants are the ‘good actors,’ ” he added.

Targets for appropriateness include the proportion of patients undergoing ablation C2 or C4 disease or greater, the mean number of ablations per patient, the mean number of ablations per limb, and the proportion of perforated ablations for greater than C4 disease. Plotting out the data for these procedures at the center level can be assessed against current thinking on best practices in the various areas. For example, “the mean number of ablations per patient has been suggested at 1.8 to be about the right number,” and he used the graph of the center performance in this area to show that most of the centers were below this objective.

In an even more appropriate example of how this kind of data could be used to determine appropriateness, Dr. Wakefield described how perforated ablations should be performed for greater than C4 disease, but not for C2 disease. He described how, according to the actual data in the registry, there have been 870 total perforated treatments recorded, 38% for C2 disease, and of these 332 procedures, almost half of these were performed at one center only, with two other centers reporting 30 such procedures. “So clearly there are three centers that are doing perforated ablations for patients that are outside the guidelines,” Dr. Wakefield pointed out.

In future, payer demand is likely to demand that each treating physician provide evidence of the appropriateness of procedures performed, as well as appropriate patient selection and adherence to best practices, and good outcomes, which is part of what a society-based registry such as the VVR can provide.

“I believe the VQI-VVR is well-positioned to meet these needs. And if we ask the question ‘can VQI be used as a benchmark for setting ethical standards,’ I think it can certainly be used to help set appropriate standards, and since appropriateness is one part of ethical standards, I believe it has a role,” he concluded.

Dr. Wakefield reported that he had no disclosures.

mlesney@mdedge.com

NEW YORK – Registry data can be used to craft guidance for determining the appropriateness of procedures at vein centers, based on data presented by Thomas W. Wakefield, MD at the 2018 Veith Symposium.

The Vascular Quality Initiative Varicose Vein Registry (VQI-VVR), initiated in 2014 by the Society for Vascular Surgery in conjunction with the American Venous Forum, captures procedures that are performed in vein centers, office-based practices, and ambulatory or inpatient settings. The VVR looks at ablation and phlebectomy techniques and captures data including patient demographics, history, procedure data, plus early and late office-based and patient-reported follow-up in order to benchmark and improve outcomes and develop best practices and to help meet vein center certification requirements. The VVR includes 39 centers and more than 23,000 procedures.

Dr. Wakefield, who heads the VVR, used this registry as a means to illustrate how VQIs could be used to establish whether “the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin that the procedure is worth doing.” This can be considered to be “appropriateness, which is part of ethical treatment.” Dr. Wakefield is the Stanley Professor of Vascular Surgery at the University of Michigan and section head, vascular surgery, University of Michigan Cardiovascular Center, Ann Arbor.

Data from the VQI registry (of which the VVR is a component) are now being used to generate appropriateness reports, said Dr. Wakefield.

The VQI represents a large comprehensive database of long-term data to define appropriate care. In addition, the VQI infrastructure is already geared to producing these reports both at a center and at a surgeon level. One disadvantage of the VVR registry, however, is low participation – only the 39 centers – and that it doesn’t capture cosmetic procedures and lesser (C1) disease. Further, it’s “likely the VQI participants are the ‘good actors,’ ” he added.

Targets for appropriateness include the proportion of patients undergoing ablation C2 or C4 disease or greater, the mean number of ablations per patient, the mean number of ablations per limb, and the proportion of perforated ablations for greater than C4 disease. Plotting out the data for these procedures at the center level can be assessed against current thinking on best practices in the various areas. For example, “the mean number of ablations per patient has been suggested at 1.8 to be about the right number,” and he used the graph of the center performance in this area to show that most of the centers were below this objective.

In an even more appropriate example of how this kind of data could be used to determine appropriateness, Dr. Wakefield described how perforated ablations should be performed for greater than C4 disease, but not for C2 disease. He described how, according to the actual data in the registry, there have been 870 total perforated treatments recorded, 38% for C2 disease, and of these 332 procedures, almost half of these were performed at one center only, with two other centers reporting 30 such procedures. “So clearly there are three centers that are doing perforated ablations for patients that are outside the guidelines,” Dr. Wakefield pointed out.

In future, payer demand is likely to demand that each treating physician provide evidence of the appropriateness of procedures performed, as well as appropriate patient selection and adherence to best practices, and good outcomes, which is part of what a society-based registry such as the VVR can provide.

“I believe the VQI-VVR is well-positioned to meet these needs. And if we ask the question ‘can VQI be used as a benchmark for setting ethical standards,’ I think it can certainly be used to help set appropriate standards, and since appropriateness is one part of ethical standards, I believe it has a role,” he concluded.

Dr. Wakefield reported that he had no disclosures.

mlesney@mdedge.com

If one includes the entire spectrum of venous disease, it is a more common pathology than peripheral arterial disease. The financial impact of venous disease is substantial. Why, then, has it taken so long to generate enthusiasm for venous disease of the femorocaval and subclaviocaval segments? For years, the endovascular management of venous disease used technology and techniques borrowed from the arterial space; although results were encouraging, it is clear that they varied widely and continue to do so. Management of these vascular beds is very reminiscent of the barrage of devices we have thrown at the superficial femoral artery.

In peripheral arterial disease, there have been much education and research focused on understanding atherosclerosis and its interaction with arterial devices. However, the paucity of investigation and enlightenment in the venous domain is evident when a literature search is performed. Certainly there are data from Comerota et al. showing an increased amount of collagen in the walls of chronically diseased veins. While this is a reasonable start, it is not sufficient data on which to build an entire treatment paradigm. Just like peripheral arterial disease, venous pathology presents in a continuum. Without an in-depth appreciation of the variability of those presentations, it is difficult to envision targeted therapies.

Although vendors have recently engaged in the development of venous-specific devices, it is in great part grounded in expert opinion rather than in hard data. The Medicare Evidence Development & Coverage Advisory Committee has made it known that we need more evidence on the efficacy of all venous procedures. Peter Gloviczki, MD, a vascular surgeon at Mayo Clinic, in Rochester, Minn., put it succinctly in an issue of Venous News: “We need to focus on venous research and never forget that whoever owns research owns the disease. We must continue innovation and collaboration, with other venous specialties and with industry.” Truth be told, there doesn’t seem to be much fascination with comprehension of the disease, but there appears to be an enormous drive from a variety of specialties to do procedures.

In July 2015, Gerard O’Sullivan, MD, wrote of a multidisciplinary group in Europe established to develop some standardization in venous stenting guidelines. He describes a “need for consistent guidelines for preoperative imaging, follow-up, anticoagulation duration and type, stent diameter, length into the inferior vena cava and lower end in relation to the internal iliac vein/external iliac vein.” I concur, that this would be utopic. I have not come across such guidelines to date.

Current basic science research focuses on pathologic considerations of venous thrombosis, including the consequences related to mechanical behavior of the venous wall in those conditions. In our group’s opinion, these considerations are elemental in determining the next steps in the research paradigm. What determines the remodeling of a vein, with or without intervention? How does a stent influence remodeling? Not surprisingly there are numerous questions that remain unanswered.

Translational investigation has provided insight into innovative ways to use computed tomography and magnetic resonance imaging. The ability to stage venous disease noninvasively could have a profound impact on how and why we manage the pathology. Additionally, knowing what the pathology looks like and potentially behaves like has the potential to promote more appropriate therapies. Intravascular ultrasound is well described by users and essential to the management of venous disease as it allows us to visualize and appreciate the pathology being treated in real time.

IVUS, though, is primarily used in the context of delivering a therapeutic tool as well as being invasive. Until recently, we have not been able to bring the power of cross-sectional imaging into the operative space. Our group has published on the use of multimodal imaging techniques such as magnetic resonance venography and fluoroscopic image fusion, which can potentially guide future interventions and optimize therapeutic decision-making.

Ultimately, we believe that diseased veins behave differently than arteries do. Therefore, managing veins with tools meant for another space is likely not ideal. Many venous interventions use arterial devices that are not optimized for venous pathologies and underline the fact that we need to continue to develop tools specifically designed for the venous space. The ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) trial has been extremely impactful in the treatment paradigm of venous thrombosis. Although the results remain heavily debated and, on some level, contested, it is a critical trial and should – in many ways – serve as an example of the good research being executed in venous disease.

A quote many have attributed to Albert Einstein says: “The one who follows the crowd will usually go no further than the crowd. Those who walk alone are likely to find themselves in places no one has ever been before.” We have an opportunity to be more enlightened with respect to central venous therapies; let’s not act like lemmings and follow one another off the cliff.

Dr. Bismuth is an associate professor of surgery and associate program director, Houston Methodist Hospital. He reported that he had no relevant disclosures.

References

Comerota AJ et al. 2015 May. Thromb Res. 135(5):882-7.

Vedantham S et al. 2017 Dec 7. N Engl J Med. 377(23):2240-52.

O’Sullivan G 2015 Jul. Endovascular Today.14;7:60-2.

Gloviczki P 2017 Apr. Venous News.1:8.














 

If one includes the entire spectrum of venous disease, it is a more common pathology than peripheral arterial disease. The financial impact of venous disease is substantial. Why, then, has it taken so long to generate enthusiasm for venous disease of the femorocaval and subclaviocaval segments? For years, the endovascular management of venous disease used technology and techniques borrowed from the arterial space; although results were encouraging, it is clear that they varied widely and continue to do so. Management of these vascular beds is very reminiscent of the barrage of devices we have thrown at the superficial femoral artery.

In peripheral arterial disease, there have been much education and research focused on understanding atherosclerosis and its interaction with arterial devices. However, the paucity of investigation and enlightenment in the venous domain is evident when a literature search is performed. Certainly there are data from Comerota et al. showing an increased amount of collagen in the walls of chronically diseased veins. While this is a reasonable start, it is not sufficient data on which to build an entire treatment paradigm. Just like peripheral arterial disease, venous pathology presents in a continuum. Without an in-depth appreciation of the variability of those presentations, it is difficult to envision targeted therapies.

Although vendors have recently engaged in the development of venous-specific devices, it is in great part grounded in expert opinion rather than in hard data. The Medicare Evidence Development & Coverage Advisory Committee has made it known that we need more evidence on the efficacy of all venous procedures. Peter Gloviczki, MD, a vascular surgeon at Mayo Clinic, in Rochester, Minn., put it succinctly in an issue of Venous News: “We need to focus on venous research and never forget that whoever owns research owns the disease. We must continue innovation and collaboration, with other venous specialties and with industry.” Truth be told, there doesn’t seem to be much fascination with comprehension of the disease, but there appears to be an enormous drive from a variety of specialties to do procedures.

In July 2015, Gerard O’Sullivan, MD, wrote of a multidisciplinary group in Europe established to develop some standardization in venous stenting guidelines. He describes a “need for consistent guidelines for preoperative imaging, follow-up, anticoagulation duration and type, stent diameter, length into the inferior vena cava and lower end in relation to the internal iliac vein/external iliac vein.” I concur, that this would be utopic. I have not come across such guidelines to date.

Current basic science research focuses on pathologic considerations of venous thrombosis, including the consequences related to mechanical behavior of the venous wall in those conditions. In our group’s opinion, these considerations are elemental in determining the next steps in the research paradigm. What determines the remodeling of a vein, with or without intervention? How does a stent influence remodeling? Not surprisingly there are numerous questions that remain unanswered.

Translational investigation has provided insight into innovative ways to use computed tomography and magnetic resonance imaging. The ability to stage venous disease noninvasively could have a profound impact on how and why we manage the pathology. Additionally, knowing what the pathology looks like and potentially behaves like has the potential to promote more appropriate therapies. Intravascular ultrasound is well described by users and essential to the management of venous disease as it allows us to visualize and appreciate the pathology being treated in real time.

IVUS, though, is primarily used in the context of delivering a therapeutic tool as well as being invasive. Until recently, we have not been able to bring the power of cross-sectional imaging into the operative space. Our group has published on the use of multimodal imaging techniques such as magnetic resonance venography and fluoroscopic image fusion, which can potentially guide future interventions and optimize therapeutic decision-making.

Ultimately, we believe that diseased veins behave differently than arteries do. Therefore, managing veins with tools meant for another space is likely not ideal. Many venous interventions use arterial devices that are not optimized for venous pathologies and underline the fact that we need to continue to develop tools specifically designed for the venous space. The ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) trial has been extremely impactful in the treatment paradigm of venous thrombosis. Although the results remain heavily debated and, on some level, contested, it is a critical trial and should – in many ways – serve as an example of the good research being executed in venous disease.

A quote many have attributed to Albert Einstein says: “The one who follows the crowd will usually go no further than the crowd. Those who walk alone are likely to find themselves in places no one has ever been before.” We have an opportunity to be more enlightened with respect to central venous therapies; let’s not act like lemmings and follow one another off the cliff.

Dr. Bismuth is an associate professor of surgery and associate program director, Houston Methodist Hospital. He reported that he had no relevant disclosures.

References

Comerota AJ et al. 2015 May. Thromb Res. 135(5):882-7.

Vedantham S et al. 2017 Dec 7. N Engl J Med. 377(23):2240-52.

O’Sullivan G 2015 Jul. Endovascular Today.14;7:60-2.

Gloviczki P 2017 Apr. Venous News.1:8.














 

If one includes the entire spectrum of venous disease, it is a more common pathology than peripheral arterial disease. The financial impact of venous disease is substantial. Why, then, has it taken so long to generate enthusiasm for venous disease of the femorocaval and subclaviocaval segments? For years, the endovascular management of venous disease used technology and techniques borrowed from the arterial space; although results were encouraging, it is clear that they varied widely and continue to do so. Management of these vascular beds is very reminiscent of the barrage of devices we have thrown at the superficial femoral artery.

In peripheral arterial disease, there have been much education and research focused on understanding atherosclerosis and its interaction with arterial devices. However, the paucity of investigation and enlightenment in the venous domain is evident when a literature search is performed. Certainly there are data from Comerota et al. showing an increased amount of collagen in the walls of chronically diseased veins. While this is a reasonable start, it is not sufficient data on which to build an entire treatment paradigm. Just like peripheral arterial disease, venous pathology presents in a continuum. Without an in-depth appreciation of the variability of those presentations, it is difficult to envision targeted therapies.

Although vendors have recently engaged in the development of venous-specific devices, it is in great part grounded in expert opinion rather than in hard data. The Medicare Evidence Development & Coverage Advisory Committee has made it known that we need more evidence on the efficacy of all venous procedures. Peter Gloviczki, MD, a vascular surgeon at Mayo Clinic, in Rochester, Minn., put it succinctly in an issue of Venous News: “We need to focus on venous research and never forget that whoever owns research owns the disease. We must continue innovation and collaboration, with other venous specialties and with industry.” Truth be told, there doesn’t seem to be much fascination with comprehension of the disease, but there appears to be an enormous drive from a variety of specialties to do procedures.

In July 2015, Gerard O’Sullivan, MD, wrote of a multidisciplinary group in Europe established to develop some standardization in venous stenting guidelines. He describes a “need for consistent guidelines for preoperative imaging, follow-up, anticoagulation duration and type, stent diameter, length into the inferior vena cava and lower end in relation to the internal iliac vein/external iliac vein.” I concur, that this would be utopic. I have not come across such guidelines to date.

Current basic science research focuses on pathologic considerations of venous thrombosis, including the consequences related to mechanical behavior of the venous wall in those conditions. In our group’s opinion, these considerations are elemental in determining the next steps in the research paradigm. What determines the remodeling of a vein, with or without intervention? How does a stent influence remodeling? Not surprisingly there are numerous questions that remain unanswered.

Translational investigation has provided insight into innovative ways to use computed tomography and magnetic resonance imaging. The ability to stage venous disease noninvasively could have a profound impact on how and why we manage the pathology. Additionally, knowing what the pathology looks like and potentially behaves like has the potential to promote more appropriate therapies. Intravascular ultrasound is well described by users and essential to the management of venous disease as it allows us to visualize and appreciate the pathology being treated in real time.

IVUS, though, is primarily used in the context of delivering a therapeutic tool as well as being invasive. Until recently, we have not been able to bring the power of cross-sectional imaging into the operative space. Our group has published on the use of multimodal imaging techniques such as magnetic resonance venography and fluoroscopic image fusion, which can potentially guide future interventions and optimize therapeutic decision-making.

Ultimately, we believe that diseased veins behave differently than arteries do. Therefore, managing veins with tools meant for another space is likely not ideal. Many venous interventions use arterial devices that are not optimized for venous pathologies and underline the fact that we need to continue to develop tools specifically designed for the venous space. The ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) trial has been extremely impactful in the treatment paradigm of venous thrombosis. Although the results remain heavily debated and, on some level, contested, it is a critical trial and should – in many ways – serve as an example of the good research being executed in venous disease.

A quote many have attributed to Albert Einstein says: “The one who follows the crowd will usually go no further than the crowd. Those who walk alone are likely to find themselves in places no one has ever been before.” We have an opportunity to be more enlightened with respect to central venous therapies; let’s not act like lemmings and follow one another off the cliff.

Dr. Bismuth is an associate professor of surgery and associate program director, Houston Methodist Hospital. He reported that he had no relevant disclosures.

References

Comerota AJ et al. 2015 May. Thromb Res. 135(5):882-7.

Vedantham S et al. 2017 Dec 7. N Engl J Med. 377(23):2240-52.

O’Sullivan G 2015 Jul. Endovascular Today.14;7:60-2.

Gloviczki P 2017 Apr. Venous News.1:8.














 

ST. LOUIS – Compared with ibuprofen, opioid pain medication offered little benefit for pain control after venous ablation surgery, in the experience of one surgical center.

BackyardProduction/Thinkstock

Sharing study results at a poster session at the annual meeting of the Midwestern Vascular Surgery Society, Jana Sacco, MD, and her colleagues found that patients who received opioid prescriptions after venous ablations did not have significantly different postsurgical pain than did those who received ibuprofen alone.

The study, conducted against the national backdrop of greater scrutiny of postsurgical opioid prescribing, was the first to look at post–venous ablation pain management strategies, said Dr. Sacco, a resident physician at Henry Ford Hospital, Detroit. Venous ablation surgery can improve quality of life for patients with varicose veins, but best practices for managing postprocedure discomfort had not been clear; some patients receive opioid pain medications, while others are directed to use ibuprofen as needed for pain control.

The retrospective, single-center study assessed pre- and postoperative pain for patients undergoing venous ablation procedures over a 2-year period, said Dr. Sacco.

Patients who were prescribed opioids were compared with patients who were simply asked to take ibuprofen for pain control.

Comparing preoperative to postoperative pain scores, Dr. Sacco and her colleagues defined a change of 2-3 points on a 0-10 Likert scale as “good” improvement; a change of 1 point was defined as “mild” improvement, and no change or worsening was defined as no improvement.

Of the 268 patients for whom postoperative follow-up data were available, 142 received opioid prescriptions, while 126 did not.

Across the entire group of patients studied, those who had moderate to severe preoperative pain had significant improvement in pain after their procedures.

Whether patients received opioid pain medication after their venous ablation was not correlated with the degree of improvement in postprocedure pain scores. Of those who saw no improvement, 30 patients (45%) received opioids and 36 (55%) did not. Of the 89 patients who saw mild postprocedure improvement in pain, 35 (40%) were not discharged on opioids, and of 65 patients who had good improvement in postprocedure pain, 44% were not discharged on opioids (P = .7 for difference across groups).

When Dr. Sacco and her fellow researchers examined such patient characteristics as sex, race, body mass index, smoking status, and CEAP venous severity classification, they did not see any significant differences in pain scores. Similarly, neither the type of procedure (radiofrequency or laser ablation) nor information on whether compression treatment was used was associated with a difference in pain scores.

Dr. Sacco and her coauthors noted that the study was limited by its retrospective nature and the fact that patients were all drawn from a single institution. Additionally, the investigators were only able to ascertain whether opioids had been prescribed, not whether – or how much – medication was actually taken by patients.

“Most patients report an improvement in symptoms after undergoing vein ablation procedures,” reported Dr. Sacco and her colleagues, and most patients also do well with nonopioid pain control regimens. “Overprescribing opioids exposes patients to the risk of narcotic overdose and chronic opioid use and should be used with caution for patients undergoing vein ablation surgery,” they wrote.

Dr. Sacco reported no outside sources of funding and no conflicts of interest.
 

koakes@mdedge.com

ST. LOUIS – Compared with ibuprofen, opioid pain medication offered little benefit for pain control after venous ablation surgery, in the experience of one surgical center.

BackyardProduction/Thinkstock

Sharing study results at a poster session at the annual meeting of the Midwestern Vascular Surgery Society, Jana Sacco, MD, and her colleagues found that patients who received opioid prescriptions after venous ablations did not have significantly different postsurgical pain than did those who received ibuprofen alone.

The study, conducted against the national backdrop of greater scrutiny of postsurgical opioid prescribing, was the first to look at post–venous ablation pain management strategies, said Dr. Sacco, a resident physician at Henry Ford Hospital, Detroit. Venous ablation surgery can improve quality of life for patients with varicose veins, but best practices for managing postprocedure discomfort had not been clear; some patients receive opioid pain medications, while others are directed to use ibuprofen as needed for pain control.

The retrospective, single-center study assessed pre- and postoperative pain for patients undergoing venous ablation procedures over a 2-year period, said Dr. Sacco.

Patients who were prescribed opioids were compared with patients who were simply asked to take ibuprofen for pain control.

Comparing preoperative to postoperative pain scores, Dr. Sacco and her colleagues defined a change of 2-3 points on a 0-10 Likert scale as “good” improvement; a change of 1 point was defined as “mild” improvement, and no change or worsening was defined as no improvement.

Of the 268 patients for whom postoperative follow-up data were available, 142 received opioid prescriptions, while 126 did not.

Across the entire group of patients studied, those who had moderate to severe preoperative pain had significant improvement in pain after their procedures.

Whether patients received opioid pain medication after their venous ablation was not correlated with the degree of improvement in postprocedure pain scores. Of those who saw no improvement, 30 patients (45%) received opioids and 36 (55%) did not. Of the 89 patients who saw mild postprocedure improvement in pain, 35 (40%) were not discharged on opioids, and of 65 patients who had good improvement in postprocedure pain, 44% were not discharged on opioids (P = .7 for difference across groups).

When Dr. Sacco and her fellow researchers examined such patient characteristics as sex, race, body mass index, smoking status, and CEAP venous severity classification, they did not see any significant differences in pain scores. Similarly, neither the type of procedure (radiofrequency or laser ablation) nor information on whether compression treatment was used was associated with a difference in pain scores.

Dr. Sacco and her coauthors noted that the study was limited by its retrospective nature and the fact that patients were all drawn from a single institution. Additionally, the investigators were only able to ascertain whether opioids had been prescribed, not whether – or how much – medication was actually taken by patients.

“Most patients report an improvement in symptoms after undergoing vein ablation procedures,” reported Dr. Sacco and her colleagues, and most patients also do well with nonopioid pain control regimens. “Overprescribing opioids exposes patients to the risk of narcotic overdose and chronic opioid use and should be used with caution for patients undergoing vein ablation surgery,” they wrote.

Dr. Sacco reported no outside sources of funding and no conflicts of interest.
 

koakes@mdedge.com

ST. LOUIS – Compared with ibuprofen, opioid pain medication offered little benefit for pain control after venous ablation surgery, in the experience of one surgical center.

BackyardProduction/Thinkstock

Sharing study results at a poster session at the annual meeting of the Midwestern Vascular Surgery Society, Jana Sacco, MD, and her colleagues found that patients who received opioid prescriptions after venous ablations did not have significantly different postsurgical pain than did those who received ibuprofen alone.

The study, conducted against the national backdrop of greater scrutiny of postsurgical opioid prescribing, was the first to look at post–venous ablation pain management strategies, said Dr. Sacco, a resident physician at Henry Ford Hospital, Detroit. Venous ablation surgery can improve quality of life for patients with varicose veins, but best practices for managing postprocedure discomfort had not been clear; some patients receive opioid pain medications, while others are directed to use ibuprofen as needed for pain control.

The retrospective, single-center study assessed pre- and postoperative pain for patients undergoing venous ablation procedures over a 2-year period, said Dr. Sacco.

Patients who were prescribed opioids were compared with patients who were simply asked to take ibuprofen for pain control.

Comparing preoperative to postoperative pain scores, Dr. Sacco and her colleagues defined a change of 2-3 points on a 0-10 Likert scale as “good” improvement; a change of 1 point was defined as “mild” improvement, and no change or worsening was defined as no improvement.

Of the 268 patients for whom postoperative follow-up data were available, 142 received opioid prescriptions, while 126 did not.

Across the entire group of patients studied, those who had moderate to severe preoperative pain had significant improvement in pain after their procedures.

Whether patients received opioid pain medication after their venous ablation was not correlated with the degree of improvement in postprocedure pain scores. Of those who saw no improvement, 30 patients (45%) received opioids and 36 (55%) did not. Of the 89 patients who saw mild postprocedure improvement in pain, 35 (40%) were not discharged on opioids, and of 65 patients who had good improvement in postprocedure pain, 44% were not discharged on opioids (P = .7 for difference across groups).

When Dr. Sacco and her fellow researchers examined such patient characteristics as sex, race, body mass index, smoking status, and CEAP venous severity classification, they did not see any significant differences in pain scores. Similarly, neither the type of procedure (radiofrequency or laser ablation) nor information on whether compression treatment was used was associated with a difference in pain scores.

Dr. Sacco and her coauthors noted that the study was limited by its retrospective nature and the fact that patients were all drawn from a single institution. Additionally, the investigators were only able to ascertain whether opioids had been prescribed, not whether – or how much – medication was actually taken by patients.

“Most patients report an improvement in symptoms after undergoing vein ablation procedures,” reported Dr. Sacco and her colleagues, and most patients also do well with nonopioid pain control regimens. “Overprescribing opioids exposes patients to the risk of narcotic overdose and chronic opioid use and should be used with caution for patients undergoing vein ablation surgery,” they wrote.

Dr. Sacco reported no outside sources of funding and no conflicts of interest.
 

koakes@mdedge.com

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

BOSTON – The use of an intravascular ultrasound (IVUS)–based scoring system could predict stent failure at 2 years in the treatment of May-Thurner syndrome, according to Steven D. Abramowitz, MD, of the MedStar Washington Hospital Center, Washington, and his colleagues.

Martin Allred/Nationwide Photographers

Dr. Abramowitz presented their research in the Vascular and Endovascular Society (VESS) sessions held at the Vascular Annual Meeting.

“IVUS has become an important adjuvant diagnostic tool in the treatment of deep venous disease, and as such may provide a useful assessment and predictive tool for treatment success in stenting of May-Thurner syndrome,” said Dr. Abramowitz.

In their study, 118 consecutive patients with May-Thurner syndrome underwent IVUS-guided stent placement from April 2009 through May 2015 at two collaborating institutions. Patients had a mean age of 46 years and included 86 (73%) women. At the time of treatment, 45, 30, 25, and 18 patients had Clinical Etiology Anatomy Pathophysiology disease 3, 4, 5, and 6, respectively.

Dr. Abramowitz described how he and his colleagues derived an IVUS-driven scoring system to assess the following categories of May-Thurner syndrome (nonocclusive or occlusive), disease chronicity (nonthrombotic, acute, or chronic), venous disease length (less than 180 mm or greater than 181 mm), venous inflow compliance (presence or absence of respiratory variation), iliocaval confluence disease involvement (present or absent), iliocaval con-fluence stenting obligation (stented or spared), and presence of perivenous collaterals before and after stenting (none or resolved).

Six of the categories were scored with 0 or 1 and one category was scored with 0, 1, or 2. Scores were tabulated for each patient at the time of initial intervention.

All 118 (100%) patients received anticoagulation and 78 (66%) were on an antiplatelet agent. Thirty-eight (32%) developed moderate in-stent stenosis, required thrombolysis, or underwent additional stenting procedures and were considered treatment failures during the observed period.

Eighty patients (68%) required no additional intervention and were considered treatment successes. The mean IVUS score for all patients was 5.22. The mean IVUS score in the treatment failure cohort was 5.64 compared with a score of 4.67 in the treatment success group, a significant difference. Patients with a score above 4 on this 7-point scale had an increased relative risk (1.6) of stent failure at 2 years.

“An IVUS-driven scoring system score of 4 or greater during initial intervention for May-Thurner syndrome predicts failure at 2 years. Additional treatment modalities should be considered at implantation to prevent failure,” said Dr. Abramowitz.

In an interview, Dr. Abramowitz added: “There is an emerging body of research regarding outcomes of deep venous intervention. However, we are still looking to generate clinically relevant data that will help guide interventionists to achieve durable technical success and long-term positive clinical outcomes for our patients.

“At this time, there is very little data to help correlate what physicians see on venography and IVUS during the treatment of May-Thurner Lesions. This data is hopefully the first step in allowing us to guide intra-operative decision making. IVUS is an excellent tool that has been proven by other studies to aid in the diagnosis and management of venous disease. With this data we also hope that it becomes a drive of patient management as well. Ideally, this data will transition into also guiding anticoagulation management, postoperative surveillance strategies and outcomes stratification for patients,” Dr. Abramowitz concluded.

mlesney@mdedge.com

BOSTON – The use of an intravascular ultrasound (IVUS)–based scoring system could predict stent failure at 2 years in the treatment of May-Thurner syndrome, according to Steven D. Abramowitz, MD, of the MedStar Washington Hospital Center, Washington, and his colleagues.

Martin Allred/Nationwide Photographers

Dr. Abramowitz presented their research in the Vascular and Endovascular Society (VESS) sessions held at the Vascular Annual Meeting.

“IVUS has become an important adjuvant diagnostic tool in the treatment of deep venous disease, and as such may provide a useful assessment and predictive tool for treatment success in stenting of May-Thurner syndrome,” said Dr. Abramowitz.

In their study, 118 consecutive patients with May-Thurner syndrome underwent IVUS-guided stent placement from April 2009 through May 2015 at two collaborating institutions. Patients had a mean age of 46 years and included 86 (73%) women. At the time of treatment, 45, 30, 25, and 18 patients had Clinical Etiology Anatomy Pathophysiology disease 3, 4, 5, and 6, respectively.

Dr. Abramowitz described how he and his colleagues derived an IVUS-driven scoring system to assess the following categories of May-Thurner syndrome (nonocclusive or occlusive), disease chronicity (nonthrombotic, acute, or chronic), venous disease length (less than 180 mm or greater than 181 mm), venous inflow compliance (presence or absence of respiratory variation), iliocaval confluence disease involvement (present or absent), iliocaval con-fluence stenting obligation (stented or spared), and presence of perivenous collaterals before and after stenting (none or resolved).

Six of the categories were scored with 0 or 1 and one category was scored with 0, 1, or 2. Scores were tabulated for each patient at the time of initial intervention.

All 118 (100%) patients received anticoagulation and 78 (66%) were on an antiplatelet agent. Thirty-eight (32%) developed moderate in-stent stenosis, required thrombolysis, or underwent additional stenting procedures and were considered treatment failures during the observed period.

Eighty patients (68%) required no additional intervention and were considered treatment successes. The mean IVUS score for all patients was 5.22. The mean IVUS score in the treatment failure cohort was 5.64 compared with a score of 4.67 in the treatment success group, a significant difference. Patients with a score above 4 on this 7-point scale had an increased relative risk (1.6) of stent failure at 2 years.

“An IVUS-driven scoring system score of 4 or greater during initial intervention for May-Thurner syndrome predicts failure at 2 years. Additional treatment modalities should be considered at implantation to prevent failure,” said Dr. Abramowitz.

In an interview, Dr. Abramowitz added: “There is an emerging body of research regarding outcomes of deep venous intervention. However, we are still looking to generate clinically relevant data that will help guide interventionists to achieve durable technical success and long-term positive clinical outcomes for our patients.

“At this time, there is very little data to help correlate what physicians see on venography and IVUS during the treatment of May-Thurner Lesions. This data is hopefully the first step in allowing us to guide intra-operative decision making. IVUS is an excellent tool that has been proven by other studies to aid in the diagnosis and management of venous disease. With this data we also hope that it becomes a drive of patient management as well. Ideally, this data will transition into also guiding anticoagulation management, postoperative surveillance strategies and outcomes stratification for patients,” Dr. Abramowitz concluded.

mlesney@mdedge.com

BOSTON – The use of an intravascular ultrasound (IVUS)–based scoring system could predict stent failure at 2 years in the treatment of May-Thurner syndrome, according to Steven D. Abramowitz, MD, of the MedStar Washington Hospital Center, Washington, and his colleagues.

Martin Allred/Nationwide Photographers

Dr. Abramowitz presented their research in the Vascular and Endovascular Society (VESS) sessions held at the Vascular Annual Meeting.

“IVUS has become an important adjuvant diagnostic tool in the treatment of deep venous disease, and as such may provide a useful assessment and predictive tool for treatment success in stenting of May-Thurner syndrome,” said Dr. Abramowitz.

In their study, 118 consecutive patients with May-Thurner syndrome underwent IVUS-guided stent placement from April 2009 through May 2015 at two collaborating institutions. Patients had a mean age of 46 years and included 86 (73%) women. At the time of treatment, 45, 30, 25, and 18 patients had Clinical Etiology Anatomy Pathophysiology disease 3, 4, 5, and 6, respectively.

Dr. Abramowitz described how he and his colleagues derived an IVUS-driven scoring system to assess the following categories of May-Thurner syndrome (nonocclusive or occlusive), disease chronicity (nonthrombotic, acute, or chronic), venous disease length (less than 180 mm or greater than 181 mm), venous inflow compliance (presence or absence of respiratory variation), iliocaval confluence disease involvement (present or absent), iliocaval con-fluence stenting obligation (stented or spared), and presence of perivenous collaterals before and after stenting (none or resolved).

Six of the categories were scored with 0 or 1 and one category was scored with 0, 1, or 2. Scores were tabulated for each patient at the time of initial intervention.

All 118 (100%) patients received anticoagulation and 78 (66%) were on an antiplatelet agent. Thirty-eight (32%) developed moderate in-stent stenosis, required thrombolysis, or underwent additional stenting procedures and were considered treatment failures during the observed period.

Eighty patients (68%) required no additional intervention and were considered treatment successes. The mean IVUS score for all patients was 5.22. The mean IVUS score in the treatment failure cohort was 5.64 compared with a score of 4.67 in the treatment success group, a significant difference. Patients with a score above 4 on this 7-point scale had an increased relative risk (1.6) of stent failure at 2 years.

“An IVUS-driven scoring system score of 4 or greater during initial intervention for May-Thurner syndrome predicts failure at 2 years. Additional treatment modalities should be considered at implantation to prevent failure,” said Dr. Abramowitz.

In an interview, Dr. Abramowitz added: “There is an emerging body of research regarding outcomes of deep venous intervention. However, we are still looking to generate clinically relevant data that will help guide interventionists to achieve durable technical success and long-term positive clinical outcomes for our patients.

“At this time, there is very little data to help correlate what physicians see on venography and IVUS during the treatment of May-Thurner Lesions. This data is hopefully the first step in allowing us to guide intra-operative decision making. IVUS is an excellent tool that has been proven by other studies to aid in the diagnosis and management of venous disease. With this data we also hope that it becomes a drive of patient management as well. Ideally, this data will transition into also guiding anticoagulation management, postoperative surveillance strategies and outcomes stratification for patients,” Dr. Abramowitz concluded.

mlesney@mdedge.com

MUNICH – In a double blow to the current, widespread routine use of low-dose aspirin and fish oil supplements for primary cardiovascular prevention in patients with diabetes, neither treatment provided any net clinical benefit in the massive, long-term ASCEND study, investigators reported at the annual congress of the European Society of Cardiology.

And, in yet another bitter pill to swallow, low-dose aspirin failed to reduce the incidence of GI cancer or any other type of cancer, compared with placebo in the study. Earlier, nondefinitive meta-analyses of much smaller randomized trials had raised the possibility of a roughly 30% reduction in the incidence of colorectal cancer in long-time users, said Jane Armitage, MD, professor of clinical trials and epidemiology at the University of Oxford (England).

“We saw no suggestion of an anticancer effect emerging over time,” Dr. Armitage said. “We did see a significant reduction in the risk of vascular events but also an increase in major bleeding such that the absolute benefits from avoiding a serious vascular event were largely counterbalanced by increased risk of bleeding. And there was no subgroup in which we could clearly define that the benefit outweighs the risk,” she added in a video interview.

ASCEND (A Study of Cardiovascular Events in Diabetes) was a randomized, blinded trial in which 15,480 U.K. patients with diabetes and no known cardiovascular disease were placed on 100 mg/day of enteric-coated aspirin or placebo and 1 g/day of omega-3 fatty acids in capsule form or placebo in a 2 x 2 factorial design and followed prospectively for a mean of 7.4 years.

The study was undertaken because, even though the value of low-dose aspirin for secondary prevention is supported by strong evidence, the medication’s value for primary prevention in patients with diabetes has long been uncertain. American Diabetes Association guidelines give a Grade C recommendation to consideration of low-dose aspirin as a primary prevention strategy in patients with diabetes having a 10-year cardiovascular risk estimated at 10% or greater.

The primary efficacy endpoint in ASCEND was the occurrence of a first serious vascular event, defined as MI, stroke, transient ischemic attack, or death from any vascular cause other than intracranial hemorrhage. The rate was 8.5% in the aspirin group and 9.6% with placebo, for a statistically significant 12% relative risk reduction. However, the rate of the primary composite safety endpoint, comprising intracranial hemorrhage, GI bleeding, sight-threatening bleeding in the eye, or other bleeding serious enough to entail a trip to the hospital, was 4.1% in the aspirin group and 3.2% with placebo, a 29% increase in risk.

Aspirin reduced the absolute risk of a serious vascular event by 1.1%, compared with placebo, while boosting the risk of major bleeding by an absolute 0.9% – essentially a wash. The number needed to treat to avoid a serious vascular event was 91 patients, with 112 being the number needed to cause a major bleeding event. The risk of major bleeding rose with increasing baseline 5-year vascular event risk.

ASCEND provided no support for a recent report suggesting the benefit of low-dose aspirin for cardioprotection is largely confined to individuals weighing less than 70 kg (Lancet. 2018; 392:387-99); in fact, the opposite appeared to be true, according to Dr. Armitage.

The incidence of cancer of the GI tract was 2.0% in both study arms. The overall cancer rate was 11.6% in the aspirin arm and 11.5% with placebo. Additional follow-up focused on cancer is planned for 5 and 10 years after the end of ASCEND in order to examine the possibility of a delayed anticancer effect, she added.

Dr. Armitage said one reason aspirin may have failed to show a significant net benefit was the high rate of background cardioprotective medication usage, especially statins and antihypertensive drugs.

“I think if your diabetes is well managed and you’ve got your other risk factors under control, you have to consider very carefully whether or not, for you, the benefits of aspirin outweigh the risks,” she concluded.

Cardiologists respond

ASCEND’s two designated discussants, both cardiologists, took a more positive view of the results than Dr. Armitage, who isn’t a cardiologist.

Bruce Jancin/MDedge News

Sigrun Halvorsen, MD, professor of cardiology at the University of Oslo, noted that most ASCEND participants were at relatively low cardiovascular risk, with an event rate of about 1.3% per year. She indicated that she’d like to see more data on higher-risk individuals before excluding any role for aspirin in primary cardiovascular prevention in patients with diabetes.

“Serious vascular events and bleeding are not necessarily equally weighted,” she added. “Most major bleeds in ASCEND were GI bleeds, and these can be largely prevented by PPIs [proton pump inhibitors], in contrast to death and stroke, which are irreversible events.”

“I think this study could be interpreted more favorably,” agreed Christopher P. Cannon, MD, professor of medicine at Harvard Medical School, Boston. “Bleeds are reversible, but MIs and whatnot are not.”

Fish oil flounders in ASCEND

Bruce Jancin/MDedge News

Louise Bowman, MD, also at the University of Oxford, presented the ASCEND fish oil findings. Over an average of 7.4 years, omega-3 fatty acid supplementation had no effect on the rate of serious vascular events, no effect on cancer, no impact on all-cause or cause-specific mortality, and raised no safety issues in patients with diabetes. She argued that current guidelines recommending fish oil supplements for cardiovascular prevention should be reconsidered.

“Certainly there doesn’t seem to be any justification for the use of this dose of omega-3 fatty acids – 1 g/day – for the prevention of cardiovascular disease,” Dr. Bowman said.

However, Dr. Cannon saw a sliver of hope within the ASCEND findings. One component of the serious vascular event composite endpoint – vascular death – occurred in 2.4% of the fish oil group and 2.9% of placebo-treated controls, for a statistically significant 19% relative risk reduction. It could be a fluke, given that none of the other vascular endpoints followed suit. But physicians and patients won’t have to wait long to find out. Another randomized trial of low-dose fish oil supplements for primary cardiovascular prevention – the nearly 26,000-patient VITAL trial – is due to report later in 2018.

In addition, two major, randomized trials of higher-dose fish oil supplementation for secondary prevention are ongoing. The roughly 8,000-patient REDUCE-IT trial is expected to report results later this year, and the STRENGTH trial, featuring more than 13,000 patients, should be completed in 2020. Both studies are heavily loaded with diabetes patients, Dr. Cannon noted.

Simultaneous with presentation of the ASCEND results at the ESC congress, the study was published online at the New England Journal of Medicine website (doi: 10.1056/NEJMoa1804988 and doi: 10.1056/NEJMoa1804989).

The ASCEND study was funded by the British Heart Foundation and the U.K. Medical Research Council with support provided by Abbott Laboratories, Bayer, Mylan, and Solvay. Dr. Armitage and Dr. Bowman reported receiving research grants from the Medicines Company, Bayer, and Mylan. Dr. Halvorsen reported no financial conflicts. Dr. Cannon reported serving as a consultant to roughly a dozen pharmaceutical companies, including the Amarin Corporation, which markets a fish oil supplement and sponsored the REDUCE-IT trial.

bjancin@mdedge.com

MUNICH – In a double blow to the current, widespread routine use of low-dose aspirin and fish oil supplements for primary cardiovascular prevention in patients with diabetes, neither treatment provided any net clinical benefit in the massive, long-term ASCEND study, investigators reported at the annual congress of the European Society of Cardiology.

And, in yet another bitter pill to swallow, low-dose aspirin failed to reduce the incidence of GI cancer or any other type of cancer, compared with placebo in the study. Earlier, nondefinitive meta-analyses of much smaller randomized trials had raised the possibility of a roughly 30% reduction in the incidence of colorectal cancer in long-time users, said Jane Armitage, MD, professor of clinical trials and epidemiology at the University of Oxford (England).

“We saw no suggestion of an anticancer effect emerging over time,” Dr. Armitage said. “We did see a significant reduction in the risk of vascular events but also an increase in major bleeding such that the absolute benefits from avoiding a serious vascular event were largely counterbalanced by increased risk of bleeding. And there was no subgroup in which we could clearly define that the benefit outweighs the risk,” she added in a video interview.

ASCEND (A Study of Cardiovascular Events in Diabetes) was a randomized, blinded trial in which 15,480 U.K. patients with diabetes and no known cardiovascular disease were placed on 100 mg/day of enteric-coated aspirin or placebo and 1 g/day of omega-3 fatty acids in capsule form or placebo in a 2 x 2 factorial design and followed prospectively for a mean of 7.4 years.

The study was undertaken because, even though the value of low-dose aspirin for secondary prevention is supported by strong evidence, the medication’s value for primary prevention in patients with diabetes has long been uncertain. American Diabetes Association guidelines give a Grade C recommendation to consideration of low-dose aspirin as a primary prevention strategy in patients with diabetes having a 10-year cardiovascular risk estimated at 10% or greater.

The primary efficacy endpoint in ASCEND was the occurrence of a first serious vascular event, defined as MI, stroke, transient ischemic attack, or death from any vascular cause other than intracranial hemorrhage. The rate was 8.5% in the aspirin group and 9.6% with placebo, for a statistically significant 12% relative risk reduction. However, the rate of the primary composite safety endpoint, comprising intracranial hemorrhage, GI bleeding, sight-threatening bleeding in the eye, or other bleeding serious enough to entail a trip to the hospital, was 4.1% in the aspirin group and 3.2% with placebo, a 29% increase in risk.

Aspirin reduced the absolute risk of a serious vascular event by 1.1%, compared with placebo, while boosting the risk of major bleeding by an absolute 0.9% – essentially a wash. The number needed to treat to avoid a serious vascular event was 91 patients, with 112 being the number needed to cause a major bleeding event. The risk of major bleeding rose with increasing baseline 5-year vascular event risk.

ASCEND provided no support for a recent report suggesting the benefit of low-dose aspirin for cardioprotection is largely confined to individuals weighing less than 70 kg (Lancet. 2018; 392:387-99); in fact, the opposite appeared to be true, according to Dr. Armitage.

The incidence of cancer of the GI tract was 2.0% in both study arms. The overall cancer rate was 11.6% in the aspirin arm and 11.5% with placebo. Additional follow-up focused on cancer is planned for 5 and 10 years after the end of ASCEND in order to examine the possibility of a delayed anticancer effect, she added.

Dr. Armitage said one reason aspirin may have failed to show a significant net benefit was the high rate of background cardioprotective medication usage, especially statins and antihypertensive drugs.

“I think if your diabetes is well managed and you’ve got your other risk factors under control, you have to consider very carefully whether or not, for you, the benefits of aspirin outweigh the risks,” she concluded.

Cardiologists respond

ASCEND’s two designated discussants, both cardiologists, took a more positive view of the results than Dr. Armitage, who isn’t a cardiologist.

Bruce Jancin/MDedge News

Sigrun Halvorsen, MD, professor of cardiology at the University of Oslo, noted that most ASCEND participants were at relatively low cardiovascular risk, with an event rate of about 1.3% per year. She indicated that she’d like to see more data on higher-risk individuals before excluding any role for aspirin in primary cardiovascular prevention in patients with diabetes.

“Serious vascular events and bleeding are not necessarily equally weighted,” she added. “Most major bleeds in ASCEND were GI bleeds, and these can be largely prevented by PPIs [proton pump inhibitors], in contrast to death and stroke, which are irreversible events.”

“I think this study could be interpreted more favorably,” agreed Christopher P. Cannon, MD, professor of medicine at Harvard Medical School, Boston. “Bleeds are reversible, but MIs and whatnot are not.”

Fish oil flounders in ASCEND

Bruce Jancin/MDedge News

Louise Bowman, MD, also at the University of Oxford, presented the ASCEND fish oil findings. Over an average of 7.4 years, omega-3 fatty acid supplementation had no effect on the rate of serious vascular events, no effect on cancer, no impact on all-cause or cause-specific mortality, and raised no safety issues in patients with diabetes. She argued that current guidelines recommending fish oil supplements for cardiovascular prevention should be reconsidered.

“Certainly there doesn’t seem to be any justification for the use of this dose of omega-3 fatty acids – 1 g/day – for the prevention of cardiovascular disease,” Dr. Bowman said.

However, Dr. Cannon saw a sliver of hope within the ASCEND findings. One component of the serious vascular event composite endpoint – vascular death – occurred in 2.4% of the fish oil group and 2.9% of placebo-treated controls, for a statistically significant 19% relative risk reduction. It could be a fluke, given that none of the other vascular endpoints followed suit. But physicians and patients won’t have to wait long to find out. Another randomized trial of low-dose fish oil supplements for primary cardiovascular prevention – the nearly 26,000-patient VITAL trial – is due to report later in 2018.

In addition, two major, randomized trials of higher-dose fish oil supplementation for secondary prevention are ongoing. The roughly 8,000-patient REDUCE-IT trial is expected to report results later this year, and the STRENGTH trial, featuring more than 13,000 patients, should be completed in 2020. Both studies are heavily loaded with diabetes patients, Dr. Cannon noted.

Simultaneous with presentation of the ASCEND results at the ESC congress, the study was published online at the New England Journal of Medicine website (doi: 10.1056/NEJMoa1804988 and doi: 10.1056/NEJMoa1804989).

The ASCEND study was funded by the British Heart Foundation and the U.K. Medical Research Council with support provided by Abbott Laboratories, Bayer, Mylan, and Solvay. Dr. Armitage and Dr. Bowman reported receiving research grants from the Medicines Company, Bayer, and Mylan. Dr. Halvorsen reported no financial conflicts. Dr. Cannon reported serving as a consultant to roughly a dozen pharmaceutical companies, including the Amarin Corporation, which markets a fish oil supplement and sponsored the REDUCE-IT trial.

bjancin@mdedge.com

MUNICH – In a double blow to the current, widespread routine use of low-dose aspirin and fish oil supplements for primary cardiovascular prevention in patients with diabetes, neither treatment provided any net clinical benefit in the massive, long-term ASCEND study, investigators reported at the annual congress of the European Society of Cardiology.

And, in yet another bitter pill to swallow, low-dose aspirin failed to reduce the incidence of GI cancer or any other type of cancer, compared with placebo in the study. Earlier, nondefinitive meta-analyses of much smaller randomized trials had raised the possibility of a roughly 30% reduction in the incidence of colorectal cancer in long-time users, said Jane Armitage, MD, professor of clinical trials and epidemiology at the University of Oxford (England).

“We saw no suggestion of an anticancer effect emerging over time,” Dr. Armitage said. “We did see a significant reduction in the risk of vascular events but also an increase in major bleeding such that the absolute benefits from avoiding a serious vascular event were largely counterbalanced by increased risk of bleeding. And there was no subgroup in which we could clearly define that the benefit outweighs the risk,” she added in a video interview.

ASCEND (A Study of Cardiovascular Events in Diabetes) was a randomized, blinded trial in which 15,480 U.K. patients with diabetes and no known cardiovascular disease were placed on 100 mg/day of enteric-coated aspirin or placebo and 1 g/day of omega-3 fatty acids in capsule form or placebo in a 2 x 2 factorial design and followed prospectively for a mean of 7.4 years.

The study was undertaken because, even though the value of low-dose aspirin for secondary prevention is supported by strong evidence, the medication’s value for primary prevention in patients with diabetes has long been uncertain. American Diabetes Association guidelines give a Grade C recommendation to consideration of low-dose aspirin as a primary prevention strategy in patients with diabetes having a 10-year cardiovascular risk estimated at 10% or greater.

The primary efficacy endpoint in ASCEND was the occurrence of a first serious vascular event, defined as MI, stroke, transient ischemic attack, or death from any vascular cause other than intracranial hemorrhage. The rate was 8.5% in the aspirin group and 9.6% with placebo, for a statistically significant 12% relative risk reduction. However, the rate of the primary composite safety endpoint, comprising intracranial hemorrhage, GI bleeding, sight-threatening bleeding in the eye, or other bleeding serious enough to entail a trip to the hospital, was 4.1% in the aspirin group and 3.2% with placebo, a 29% increase in risk.

Aspirin reduced the absolute risk of a serious vascular event by 1.1%, compared with placebo, while boosting the risk of major bleeding by an absolute 0.9% – essentially a wash. The number needed to treat to avoid a serious vascular event was 91 patients, with 112 being the number needed to cause a major bleeding event. The risk of major bleeding rose with increasing baseline 5-year vascular event risk.

ASCEND provided no support for a recent report suggesting the benefit of low-dose aspirin for cardioprotection is largely confined to individuals weighing less than 70 kg (Lancet. 2018; 392:387-99); in fact, the opposite appeared to be true, according to Dr. Armitage.

The incidence of cancer of the GI tract was 2.0% in both study arms. The overall cancer rate was 11.6% in the aspirin arm and 11.5% with placebo. Additional follow-up focused on cancer is planned for 5 and 10 years after the end of ASCEND in order to examine the possibility of a delayed anticancer effect, she added.

Dr. Armitage said one reason aspirin may have failed to show a significant net benefit was the high rate of background cardioprotective medication usage, especially statins and antihypertensive drugs.

“I think if your diabetes is well managed and you’ve got your other risk factors under control, you have to consider very carefully whether or not, for you, the benefits of aspirin outweigh the risks,” she concluded.

Cardiologists respond

ASCEND’s two designated discussants, both cardiologists, took a more positive view of the results than Dr. Armitage, who isn’t a cardiologist.

Bruce Jancin/MDedge News

Sigrun Halvorsen, MD, professor of cardiology at the University of Oslo, noted that most ASCEND participants were at relatively low cardiovascular risk, with an event rate of about 1.3% per year. She indicated that she’d like to see more data on higher-risk individuals before excluding any role for aspirin in primary cardiovascular prevention in patients with diabetes.

“Serious vascular events and bleeding are not necessarily equally weighted,” she added. “Most major bleeds in ASCEND were GI bleeds, and these can be largely prevented by PPIs [proton pump inhibitors], in contrast to death and stroke, which are irreversible events.”

“I think this study could be interpreted more favorably,” agreed Christopher P. Cannon, MD, professor of medicine at Harvard Medical School, Boston. “Bleeds are reversible, but MIs and whatnot are not.”

Fish oil flounders in ASCEND

Bruce Jancin/MDedge News

Louise Bowman, MD, also at the University of Oxford, presented the ASCEND fish oil findings. Over an average of 7.4 years, omega-3 fatty acid supplementation had no effect on the rate of serious vascular events, no effect on cancer, no impact on all-cause or cause-specific mortality, and raised no safety issues in patients with diabetes. She argued that current guidelines recommending fish oil supplements for cardiovascular prevention should be reconsidered.

“Certainly there doesn’t seem to be any justification for the use of this dose of omega-3 fatty acids – 1 g/day – for the prevention of cardiovascular disease,” Dr. Bowman said.

However, Dr. Cannon saw a sliver of hope within the ASCEND findings. One component of the serious vascular event composite endpoint – vascular death – occurred in 2.4% of the fish oil group and 2.9% of placebo-treated controls, for a statistically significant 19% relative risk reduction. It could be a fluke, given that none of the other vascular endpoints followed suit. But physicians and patients won’t have to wait long to find out. Another randomized trial of low-dose fish oil supplements for primary cardiovascular prevention – the nearly 26,000-patient VITAL trial – is due to report later in 2018.

In addition, two major, randomized trials of higher-dose fish oil supplementation for secondary prevention are ongoing. The roughly 8,000-patient REDUCE-IT trial is expected to report results later this year, and the STRENGTH trial, featuring more than 13,000 patients, should be completed in 2020. Both studies are heavily loaded with diabetes patients, Dr. Cannon noted.

Simultaneous with presentation of the ASCEND results at the ESC congress, the study was published online at the New England Journal of Medicine website (doi: 10.1056/NEJMoa1804988 and doi: 10.1056/NEJMoa1804989).

The ASCEND study was funded by the British Heart Foundation and the U.K. Medical Research Council with support provided by Abbott Laboratories, Bayer, Mylan, and Solvay. Dr. Armitage and Dr. Bowman reported receiving research grants from the Medicines Company, Bayer, and Mylan. Dr. Halvorsen reported no financial conflicts. Dr. Cannon reported serving as a consultant to roughly a dozen pharmaceutical companies, including the Amarin Corporation, which markets a fish oil supplement and sponsored the REDUCE-IT trial.

bjancin@mdedge.com