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Anticoagulation Hub contains news and clinical review articles for physicians seeking the most up-to-date information on the rapidly evolving treatment options for preventing stroke, acute coronary events, deep vein thrombosis, and pulmonary embolism in at-risk patients. The Anticoagulation Hub is powered by Frontline Medical Communications.
Marijuana use triples risk of death from hypertension
The risk of death from hypertension is three times greater in adults who use marijuana, compared with nonusers, based on data from a retrospective study of 1,213 adults.
Changes in the legalization of marijuana may promote increased recreational use, but data on the long-term effects of marijuana use on cardiovascular and cerebrovascular mortality are limited, wrote Barbara A. Yankey, PhD, of Georgia State University, Atlanta, and her colleagues.
Data on 686 users and 527 nonusers were combined with the 2011 mortality data from the National Center for Health Statistics (Eur J Prev Cardiol. 2017 Aug 9; doi: 10.1177/2047487317723212).
Overall, marijuana users had a 3.42 times greater risk of death from hypertension than did nonusers (95% confidence interval, 1.20-9.79), and the risk increased by 1.04 for each year of use (95% CI, 1.00-1.07). The average duration of marijuana use was 11.5 years. At the time of study entry, the average age of the participants was 38 years, and the average body mass index was 29 kg/m2; 23% of marijuana users and 21% of nonusers had a prior diagnosis of hypertension.
Of the study participants, 20% used marijuana and smoked cigarettes, 16% used marijuana and were past smokers, 5% were past smokers, and 4% only smoked cigarettes. “In our study, increase in risk for hypertension, [heart disease], or cerebrovascular disease mortality associated with cigarette use was not significant,” the researchers wrote. They attributed this factor to the small sample size and noted that the dangers of cigarette smoking to the cardiovascular system are well established.
The study findings were limited by the relatively small sample size and potentially inaccurate data on the duration of marijuana use, the researchers said.
However, the results suggest that “cardiovascular risk associated with marijuana use may be greater than the cardiovascular risk already established for cigarette smoking,” and longitudinal studies are warranted, they concluded.
The researchers had no financial conflicts to disclose.
The risk of death from hypertension is three times greater in adults who use marijuana, compared with nonusers, based on data from a retrospective study of 1,213 adults.
Changes in the legalization of marijuana may promote increased recreational use, but data on the long-term effects of marijuana use on cardiovascular and cerebrovascular mortality are limited, wrote Barbara A. Yankey, PhD, of Georgia State University, Atlanta, and her colleagues.
Data on 686 users and 527 nonusers were combined with the 2011 mortality data from the National Center for Health Statistics (Eur J Prev Cardiol. 2017 Aug 9; doi: 10.1177/2047487317723212).
Overall, marijuana users had a 3.42 times greater risk of death from hypertension than did nonusers (95% confidence interval, 1.20-9.79), and the risk increased by 1.04 for each year of use (95% CI, 1.00-1.07). The average duration of marijuana use was 11.5 years. At the time of study entry, the average age of the participants was 38 years, and the average body mass index was 29 kg/m2; 23% of marijuana users and 21% of nonusers had a prior diagnosis of hypertension.
Of the study participants, 20% used marijuana and smoked cigarettes, 16% used marijuana and were past smokers, 5% were past smokers, and 4% only smoked cigarettes. “In our study, increase in risk for hypertension, [heart disease], or cerebrovascular disease mortality associated with cigarette use was not significant,” the researchers wrote. They attributed this factor to the small sample size and noted that the dangers of cigarette smoking to the cardiovascular system are well established.
The study findings were limited by the relatively small sample size and potentially inaccurate data on the duration of marijuana use, the researchers said.
However, the results suggest that “cardiovascular risk associated with marijuana use may be greater than the cardiovascular risk already established for cigarette smoking,” and longitudinal studies are warranted, they concluded.
The researchers had no financial conflicts to disclose.
The risk of death from hypertension is three times greater in adults who use marijuana, compared with nonusers, based on data from a retrospective study of 1,213 adults.
Changes in the legalization of marijuana may promote increased recreational use, but data on the long-term effects of marijuana use on cardiovascular and cerebrovascular mortality are limited, wrote Barbara A. Yankey, PhD, of Georgia State University, Atlanta, and her colleagues.
Data on 686 users and 527 nonusers were combined with the 2011 mortality data from the National Center for Health Statistics (Eur J Prev Cardiol. 2017 Aug 9; doi: 10.1177/2047487317723212).
Overall, marijuana users had a 3.42 times greater risk of death from hypertension than did nonusers (95% confidence interval, 1.20-9.79), and the risk increased by 1.04 for each year of use (95% CI, 1.00-1.07). The average duration of marijuana use was 11.5 years. At the time of study entry, the average age of the participants was 38 years, and the average body mass index was 29 kg/m2; 23% of marijuana users and 21% of nonusers had a prior diagnosis of hypertension.
Of the study participants, 20% used marijuana and smoked cigarettes, 16% used marijuana and were past smokers, 5% were past smokers, and 4% only smoked cigarettes. “In our study, increase in risk for hypertension, [heart disease], or cerebrovascular disease mortality associated with cigarette use was not significant,” the researchers wrote. They attributed this factor to the small sample size and noted that the dangers of cigarette smoking to the cardiovascular system are well established.
The study findings were limited by the relatively small sample size and potentially inaccurate data on the duration of marijuana use, the researchers said.
However, the results suggest that “cardiovascular risk associated with marijuana use may be greater than the cardiovascular risk already established for cigarette smoking,” and longitudinal studies are warranted, they concluded.
The researchers had no financial conflicts to disclose.
FROM THE EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
Key clinical point: A history of marijuana use significantly increases the risk of death from hypertension.
Major finding: Marijuana users had a 3.42 times higher risk of death from hypertension and a 1.04 times increased risk of death for each year of use.
Data source: A retrospective study of 1,213 adults aged 20 years and older using data from National Health and Nutrition Examination Survey and the National Center for Health Statistics.
Disclosures: The researchers had no financial conflicts to disclose.
VIDEO: Triple therapy study and new recommendations provide guidance on CAPS
MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.
Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).
CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.
At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.
CAPS Registry study
The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.
Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.
The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.
“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.
The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.
Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.
“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.
While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.
All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).
“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.
“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”
Guidelines
A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.
Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.
The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.
All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:
- Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
- Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
- Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
- Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
- Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
- Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
- Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.
The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.
None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.
MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.
Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).
CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.
At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.
CAPS Registry study
The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.
Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.
The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.
“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.
The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.
Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.
“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.
While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.
All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).
“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.
“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”
Guidelines
A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.
Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.
The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.
All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:
- Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
- Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
- Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
- Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
- Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
- Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
- Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.
The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.
None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.
MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.
Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).
CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.
At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.
CAPS Registry study
The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.
Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.
The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.
“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.
The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.
Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.
“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.
While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.
All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).
“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.
“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”
Guidelines
A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.
Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.
The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.
All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:
- Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
- Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
- Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
- Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
- Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
- Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
- Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.
The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.
None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Mortality was 28% with triple therapy, 41% with other combinations of treatments, and 75% with none of these treatments.
Data source: A registry study of 471 CAPS patients and clinical practice guidelines for CAPS.
Disclosures: None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.
Childhood poverty sets stage for adult heart disease
Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.
“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.
The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).
“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.
The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.
In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.
The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.
The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).
The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.
Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.
“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.
The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).
“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.
The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.
In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.
The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.
The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).
The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.
Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.
“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.
The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).
“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.
The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.
In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.
The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.
The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).
The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point: Low socioeconomic status of families was significantly linked with thicker carotid arteries in children at age 11-12 years, which could increase the risk of stroke in adulthood.
Major finding: Children in the lowest socioeconomic group at age 11-12 years were 46% more likely to have carotid intima-media thickness at a level above the 75th percentile.
Data source: A longitudinal study of children from 1,477 families in Australia.
Disclosures: The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.
Stopping statins after stroke may up recurrent stroke risk
Discontinuing statin therapy 3-6 months after a stroke may increase the risk of recurrent stroke within a year, according to findings from a large retrospective Taiwanese cohort study.
And being older or male in the Stroke Belt increases the likelihood that statins won’t be prescribed at all at the time of hospital discharge after a stroke, a separate cohort study from the United States suggests.
Both studies were reported online in the Journal of the American Heart Association.
Of 45,151 ischemic stroke patients from the Taiwan National Health Insurance Research Database who were on a moderate- or high-intensity statin within 90 days of discharge after an ischemic stroke between 2001 and 2012, 3,175 (7%) were on a reduced dosage by the 90- to 180-day period, and 8,353 (18.5%) were not on any statin by that period. After adjustment for numerous factors including age, sex, several comorbid conditions, and stroke severity index, discontinuation of statins was associated with an increased hazard of recurrent ischemic or hemorrhagic stroke (6.2% vs. 4.4%; adjusted hazard ratio [HR], 1.42), Meng Lee, MD, of Chang Gung Memorial Hospital, Chiayi Branch, Puzy, Taiwan and colleagues reported.
Discontinuation of statins was also linked to higher risks of ischemic stroke (5.6% vs. 3.9%, adjusted HR, 1.45), all-cause mortality (1.4% vs. 1%; adjusted HR, 1.37), all major events (7.8% vs. 5.6%, adjusted HR 1.38), and any hospitalization (31.7% vs. 27.1%; adjusted HR, 1.19), but had neutral effects on intracerebral hemorrhage and myocardial infarction.
“Reduced dosage statin therapy was not associated with increased risks of ischemic stroke, intracerebral hemorrhage, all-cause mortality, myocardial infarction, or all major events,” they said.
The findings support and extend those of some prior studies, and the study “affirms the deleterious effect of stopping statins after the initial period following a stroke,” they noted, adding: “Our study has both clinical and policy implications ... After a stroke due to large or small vessel atherosclerosis, patients are at high risk of recurrent stroke and should be treated aggressively in the absence of clear contraindications. Physicians also need to increase awareness among stroke patients about the potential risk of discontinuing their medications and to encourage greater adherence.”
Statin therapy should not be discontinued in the absence of a “highly compelling reason for doing so,” they added, concluding that prospective studies are needed to clarify the mechanisms underlying the association between statin discontinuation and higher recurrent stroke risk.
In a press statement, Dr. Lee said that based on these “real world” findings, statins should be a lifelong therapy for ischemic stroke patients who need a statin to lower cholesterol.
“Discontinuation of statin treatment in patients with ischemic stroke should be strongly discouraged in any stage, acute or chronic, of stroke,” Dr. Lee said. “Shifting to low-intensity statin therapy could be an alternative for stroke patients not able to tolerate moderate or high-intensity statin therapy in the years following a stroke.”
As for the findings regarding starting statin therapy at the time of discharge, an analysis of discharge prescriptions for U.S. ischemic stroke patients from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study showed that 48.7% of 323 patients who were not statin users at the time of admission and who had no history of atrial fibrillation were prescribed a statin at discharge.
Overall, after adjustment for age, race, sex, numerous comorbid conditions, impaired cognition, current smoking status, stroke buckle or Stroke Belt residence, and other factors, patients aged 65 years and older were less likely to receive a statin prescription at discharge (risk ratio, 0.75), and those with dyslipidemia were more likely to be prescribed a stain at discharge (risk ratio, 1.67), Karen C. Albright, PhD, DO, of the Birmingham (Ala.) VA Medical Center, and her colleagues found.
Further, there were no significant overall differences in statin prescribing by race (black:white risk ratio, 1.13), or by sex (male:female risk ratio, 0.97).
When subjects were analyzed based on Stroke Belt residence (defined as residence in Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia), adults aged 65 and older in the Stroke Belt were 47% less likely to be discharged on a statin, compared with younger patients (risk ratio, 0.53). This association was not observed in non–Stroke Belt residents (risk ratio, 1.14), the investigators found (J Am Heart Assoc. 2017 Aug 2. doi: 10.1161/JAHA.117.005523).
Also, among non–Stroke Belt residents, blacks were more likely to be discharged on a statin (risk ratio, 1.42), but this association was not seen in the Stroke Belt (risk ratio, 0.93).
Male Stroke Belt residents were 31% less likely than were female Stroke Belt residents to be discharged on a statin (risk ratio, 0.69), while men who were non–Stroke Belt residents were more likely than were female non–Stroke Belt residents to be discharged on a statin (risk ratio 1.38).
“Although statin prescribing increased over time in the current study, statins were prescribed at discharge to only 49% of patients with ischemic stroke. This represents a treatment gap given current American College of Cardiology/American Heart Association recommendations,” the investigators wrote.
This gap was particularly seen in men and those over aged 65 years – but not among blacks – in the Stroke Belt.
This leaves the reasons for higher rates of recurrent stroke in blacks unresolved, they noted.
“A next step in our efforts to understand the reasons for the higher rate of recurrent stroke in blacks is to evaluate statin adherence in ischemic stroke survivors,” they said.
The Taiwanese cohort study was funded by the Ministry of Science and Technology, Taiwan and Chang Gung Memorial Hospital, Taiwan. Dr. Lee and colleagues reported having no disclosures. The REGARDS study was funded by the National Institutes of Health and the Department of Health and Human Services. Dr. Albright reported having no disclosures, as did all other authors except Paul Muntner, PhD, who receives research support from Amgen Inc.
Discontinuing statin therapy 3-6 months after a stroke may increase the risk of recurrent stroke within a year, according to findings from a large retrospective Taiwanese cohort study.
And being older or male in the Stroke Belt increases the likelihood that statins won’t be prescribed at all at the time of hospital discharge after a stroke, a separate cohort study from the United States suggests.
Both studies were reported online in the Journal of the American Heart Association.
Of 45,151 ischemic stroke patients from the Taiwan National Health Insurance Research Database who were on a moderate- or high-intensity statin within 90 days of discharge after an ischemic stroke between 2001 and 2012, 3,175 (7%) were on a reduced dosage by the 90- to 180-day period, and 8,353 (18.5%) were not on any statin by that period. After adjustment for numerous factors including age, sex, several comorbid conditions, and stroke severity index, discontinuation of statins was associated with an increased hazard of recurrent ischemic or hemorrhagic stroke (6.2% vs. 4.4%; adjusted hazard ratio [HR], 1.42), Meng Lee, MD, of Chang Gung Memorial Hospital, Chiayi Branch, Puzy, Taiwan and colleagues reported.
Discontinuation of statins was also linked to higher risks of ischemic stroke (5.6% vs. 3.9%, adjusted HR, 1.45), all-cause mortality (1.4% vs. 1%; adjusted HR, 1.37), all major events (7.8% vs. 5.6%, adjusted HR 1.38), and any hospitalization (31.7% vs. 27.1%; adjusted HR, 1.19), but had neutral effects on intracerebral hemorrhage and myocardial infarction.
“Reduced dosage statin therapy was not associated with increased risks of ischemic stroke, intracerebral hemorrhage, all-cause mortality, myocardial infarction, or all major events,” they said.
The findings support and extend those of some prior studies, and the study “affirms the deleterious effect of stopping statins after the initial period following a stroke,” they noted, adding: “Our study has both clinical and policy implications ... After a stroke due to large or small vessel atherosclerosis, patients are at high risk of recurrent stroke and should be treated aggressively in the absence of clear contraindications. Physicians also need to increase awareness among stroke patients about the potential risk of discontinuing their medications and to encourage greater adherence.”
Statin therapy should not be discontinued in the absence of a “highly compelling reason for doing so,” they added, concluding that prospective studies are needed to clarify the mechanisms underlying the association between statin discontinuation and higher recurrent stroke risk.
In a press statement, Dr. Lee said that based on these “real world” findings, statins should be a lifelong therapy for ischemic stroke patients who need a statin to lower cholesterol.
“Discontinuation of statin treatment in patients with ischemic stroke should be strongly discouraged in any stage, acute or chronic, of stroke,” Dr. Lee said. “Shifting to low-intensity statin therapy could be an alternative for stroke patients not able to tolerate moderate or high-intensity statin therapy in the years following a stroke.”
As for the findings regarding starting statin therapy at the time of discharge, an analysis of discharge prescriptions for U.S. ischemic stroke patients from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study showed that 48.7% of 323 patients who were not statin users at the time of admission and who had no history of atrial fibrillation were prescribed a statin at discharge.
Overall, after adjustment for age, race, sex, numerous comorbid conditions, impaired cognition, current smoking status, stroke buckle or Stroke Belt residence, and other factors, patients aged 65 years and older were less likely to receive a statin prescription at discharge (risk ratio, 0.75), and those with dyslipidemia were more likely to be prescribed a stain at discharge (risk ratio, 1.67), Karen C. Albright, PhD, DO, of the Birmingham (Ala.) VA Medical Center, and her colleagues found.
Further, there were no significant overall differences in statin prescribing by race (black:white risk ratio, 1.13), or by sex (male:female risk ratio, 0.97).
When subjects were analyzed based on Stroke Belt residence (defined as residence in Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia), adults aged 65 and older in the Stroke Belt were 47% less likely to be discharged on a statin, compared with younger patients (risk ratio, 0.53). This association was not observed in non–Stroke Belt residents (risk ratio, 1.14), the investigators found (J Am Heart Assoc. 2017 Aug 2. doi: 10.1161/JAHA.117.005523).
Also, among non–Stroke Belt residents, blacks were more likely to be discharged on a statin (risk ratio, 1.42), but this association was not seen in the Stroke Belt (risk ratio, 0.93).
Male Stroke Belt residents were 31% less likely than were female Stroke Belt residents to be discharged on a statin (risk ratio, 0.69), while men who were non–Stroke Belt residents were more likely than were female non–Stroke Belt residents to be discharged on a statin (risk ratio 1.38).
“Although statin prescribing increased over time in the current study, statins were prescribed at discharge to only 49% of patients with ischemic stroke. This represents a treatment gap given current American College of Cardiology/American Heart Association recommendations,” the investigators wrote.
This gap was particularly seen in men and those over aged 65 years – but not among blacks – in the Stroke Belt.
This leaves the reasons for higher rates of recurrent stroke in blacks unresolved, they noted.
“A next step in our efforts to understand the reasons for the higher rate of recurrent stroke in blacks is to evaluate statin adherence in ischemic stroke survivors,” they said.
The Taiwanese cohort study was funded by the Ministry of Science and Technology, Taiwan and Chang Gung Memorial Hospital, Taiwan. Dr. Lee and colleagues reported having no disclosures. The REGARDS study was funded by the National Institutes of Health and the Department of Health and Human Services. Dr. Albright reported having no disclosures, as did all other authors except Paul Muntner, PhD, who receives research support from Amgen Inc.
Discontinuing statin therapy 3-6 months after a stroke may increase the risk of recurrent stroke within a year, according to findings from a large retrospective Taiwanese cohort study.
And being older or male in the Stroke Belt increases the likelihood that statins won’t be prescribed at all at the time of hospital discharge after a stroke, a separate cohort study from the United States suggests.
Both studies were reported online in the Journal of the American Heart Association.
Of 45,151 ischemic stroke patients from the Taiwan National Health Insurance Research Database who were on a moderate- or high-intensity statin within 90 days of discharge after an ischemic stroke between 2001 and 2012, 3,175 (7%) were on a reduced dosage by the 90- to 180-day period, and 8,353 (18.5%) were not on any statin by that period. After adjustment for numerous factors including age, sex, several comorbid conditions, and stroke severity index, discontinuation of statins was associated with an increased hazard of recurrent ischemic or hemorrhagic stroke (6.2% vs. 4.4%; adjusted hazard ratio [HR], 1.42), Meng Lee, MD, of Chang Gung Memorial Hospital, Chiayi Branch, Puzy, Taiwan and colleagues reported.
Discontinuation of statins was also linked to higher risks of ischemic stroke (5.6% vs. 3.9%, adjusted HR, 1.45), all-cause mortality (1.4% vs. 1%; adjusted HR, 1.37), all major events (7.8% vs. 5.6%, adjusted HR 1.38), and any hospitalization (31.7% vs. 27.1%; adjusted HR, 1.19), but had neutral effects on intracerebral hemorrhage and myocardial infarction.
“Reduced dosage statin therapy was not associated with increased risks of ischemic stroke, intracerebral hemorrhage, all-cause mortality, myocardial infarction, or all major events,” they said.
The findings support and extend those of some prior studies, and the study “affirms the deleterious effect of stopping statins after the initial period following a stroke,” they noted, adding: “Our study has both clinical and policy implications ... After a stroke due to large or small vessel atherosclerosis, patients are at high risk of recurrent stroke and should be treated aggressively in the absence of clear contraindications. Physicians also need to increase awareness among stroke patients about the potential risk of discontinuing their medications and to encourage greater adherence.”
Statin therapy should not be discontinued in the absence of a “highly compelling reason for doing so,” they added, concluding that prospective studies are needed to clarify the mechanisms underlying the association between statin discontinuation and higher recurrent stroke risk.
In a press statement, Dr. Lee said that based on these “real world” findings, statins should be a lifelong therapy for ischemic stroke patients who need a statin to lower cholesterol.
“Discontinuation of statin treatment in patients with ischemic stroke should be strongly discouraged in any stage, acute or chronic, of stroke,” Dr. Lee said. “Shifting to low-intensity statin therapy could be an alternative for stroke patients not able to tolerate moderate or high-intensity statin therapy in the years following a stroke.”
As for the findings regarding starting statin therapy at the time of discharge, an analysis of discharge prescriptions for U.S. ischemic stroke patients from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study showed that 48.7% of 323 patients who were not statin users at the time of admission and who had no history of atrial fibrillation were prescribed a statin at discharge.
Overall, after adjustment for age, race, sex, numerous comorbid conditions, impaired cognition, current smoking status, stroke buckle or Stroke Belt residence, and other factors, patients aged 65 years and older were less likely to receive a statin prescription at discharge (risk ratio, 0.75), and those with dyslipidemia were more likely to be prescribed a stain at discharge (risk ratio, 1.67), Karen C. Albright, PhD, DO, of the Birmingham (Ala.) VA Medical Center, and her colleagues found.
Further, there were no significant overall differences in statin prescribing by race (black:white risk ratio, 1.13), or by sex (male:female risk ratio, 0.97).
When subjects were analyzed based on Stroke Belt residence (defined as residence in Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia), adults aged 65 and older in the Stroke Belt were 47% less likely to be discharged on a statin, compared with younger patients (risk ratio, 0.53). This association was not observed in non–Stroke Belt residents (risk ratio, 1.14), the investigators found (J Am Heart Assoc. 2017 Aug 2. doi: 10.1161/JAHA.117.005523).
Also, among non–Stroke Belt residents, blacks were more likely to be discharged on a statin (risk ratio, 1.42), but this association was not seen in the Stroke Belt (risk ratio, 0.93).
Male Stroke Belt residents were 31% less likely than were female Stroke Belt residents to be discharged on a statin (risk ratio, 0.69), while men who were non–Stroke Belt residents were more likely than were female non–Stroke Belt residents to be discharged on a statin (risk ratio 1.38).
“Although statin prescribing increased over time in the current study, statins were prescribed at discharge to only 49% of patients with ischemic stroke. This represents a treatment gap given current American College of Cardiology/American Heart Association recommendations,” the investigators wrote.
This gap was particularly seen in men and those over aged 65 years – but not among blacks – in the Stroke Belt.
This leaves the reasons for higher rates of recurrent stroke in blacks unresolved, they noted.
“A next step in our efforts to understand the reasons for the higher rate of recurrent stroke in blacks is to evaluate statin adherence in ischemic stroke survivors,” they said.
The Taiwanese cohort study was funded by the Ministry of Science and Technology, Taiwan and Chang Gung Memorial Hospital, Taiwan. Dr. Lee and colleagues reported having no disclosures. The REGARDS study was funded by the National Institutes of Health and the Department of Health and Human Services. Dr. Albright reported having no disclosures, as did all other authors except Paul Muntner, PhD, who receives research support from Amgen Inc.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point:
Major finding: Discontinuation of statins 90-180 days after ischemic stroke was associated with an increased hazard of recurrent ischemic or hemorrhagic stroke (6.2% vs. 4.4%; adjusted hazard ratio [HR], 1.42).
Data source: Cohort studies in Taiwan and the United States involving 45,151 and 323 patients, respectively.
Disclosures: The Taiwanese cohort study was funded by the Ministry of Science and Technology, Taiwan and Chang Gung Memorial Hospital, Taiwan. Dr. Lee and colleagues reported having no disclosures. The REGARDS study was funded by the National Institutes of Health and the Department of Health and Human Services. Dr. Albright reported having no disclosures, as did all other authors except Paul Muntner, PhD, who receives research support from Amgen Inc.
Novel drug-eluting coronary stent looks good in DESSOLVE III
PARIS – A unique drug-eluting coronary stent showed positive interim results in the DESSOLVE III trial presented at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
In DESSOLVE III, 1,398 patients undergoing percutaneous coronary intervention were randomized to the widely used Xience everolimus-eluting stent or to MiStent, a novel thin-strut stent with a polymer coating that is quickly absorbed after delivering microcrystalline sirolimus into the vessel wall for prolonged release at a near-linear rate.
At an interim analysis at 12 months of follow-up, the primary endpoint – a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization – had occurred in 5.8% of the MiStent group and 6.5% of Xience recipients in the study, which was designed as a noninferiority trial, reported Robbert J. de Winter, MD, professor of clinical cardiology at the Academic Medical Center in Amsterdam.
“The data support the hypothesis that long-term cytostatic inhibition of early neointima could prevent the late neointimal growth seen at medium and long term with conventional drug-eluting stents,” he said.
MiStent is designed to overcome a shortcoming of conventional drug-eluting stents: namely, their durable polymer coating sticks around after the cytostatic drug is finished being released. It is believed that this residual polymer, which may not disappear for 6-9 months, induces inflammation in the vessel wall, eventually leading to intimal growth, restenosis, and new atherosclerosis.
“The unique feature of the MiStent is that the polymer is bioabsorbable and is fully absorbed at 3 months, whereas the drug is present in the vessel wall out to 9 months, well after the coating has disappeared. So in theory you would expect that any inflammatory response caused by the polymer coating will be counteracted by the drug. This was seen in animal models. And in the DESSOLVE I and II studies, angiographic follow-up showed that late luminal loss was flat after 6 months, in contrast to other drug-eluting stents, which show accrual of late neointimal growth after 6 months to a year,” according to the cardiologist.
DESSOLVE III is planned as a 3-year study. Already by 6 months the curves for target lesion revascularization started to separate, with a 12-month rate of 2.6% in the MiStent group versus 3.8% for Xience. And while this difference is not yet statistically significant, Dr. de Winter and his coinvestigators expect that by 3 years the separation will have grown to the point that the difference becomes statistically significant and clinically meaningful.
The MiStent platform is composed of a cobalt/chromium alloy. The stent strut thickness is only 64 microns, in contrast to 81 microns for the Xience stent. Thinner stent struts have previously been shown to be less injurious to the vessel wall.
DESSOLVE III is an all-comers trial conducted at 20 sites in four European countries. Participants had to have a reference vessel diameter of 2.5-3.5 mm. Roughly 60% of patients had an acute coronary syndrome as their indication for PCI. The study population included, among others, patients with left main coronary artery lesions, restenotic lesions, and failed saphenous vein grafts. Dual-antiplatelet therapy was given for 6 months in patients with stable angina and 12 months for those with ACS, in accordance with European Society of Cardiology guidelines.
Discussant Robert A. Byrne, MD, of the German Heart Center in Munich, declared: “For me, this is a potentially interesting device. It’s the only device where we have a drug elution that’s more prolonged than the polymer, and this does offer the potential for later benefit.”
Dr. Byrne was a member of a European Commission–backed task force that developed European regulatory guidance for the evaluation of new coronary stents. “This MiStent trial program ticks off a lot of boxes: We had a successful first human use study, then we had a modest-size angiographic endpoint study where the late lumen loss looked good, and now we have a clinical endpoint study. This is what we want to see in the regulatory space.”
Another discussant, Chaim Lotan, MD, pronounced the MiStent “definitely another good stent on the shelf.”
It’s impossible to say whether the excellent 1-year outcomes seen with MiStent in DESSOLVE III were due to the prolonged-release microcrystalline sirolimus, the ultrathin stent struts, or both. In any case, the major adverse cardiovascular event rates seen in DESSOLVE III are so low by historical standards that it will become extremely difficult to show superiority for one contemporary drug-eluting stent over another, predicted Dr. Lotan of Hadassah Medical Center in Jerusalem.
Dr. de Winter concurred.
“I think we can now say that the benchmark for present day drug-eluting stents is a target lesion failure rate of about 6% at 12 months and a stent thrombosis rate below 1% at 12 months. It’s going to be increasingly more difficult to improve on that,” he said.
The MiStent, manufactured by Micell Technologies, is commercially available in Europe but investigational in the United States.
DESSOLVE III was sponsored by the European Cardiovascular Research Institute and supported by grants from Micell Technologies and Stentys.
Dr. de Winter reported receiving research grants from OrbusNeich, Abbott Vascular, AstraZeneca, Stentys, and Tryton.
PARIS – A unique drug-eluting coronary stent showed positive interim results in the DESSOLVE III trial presented at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
In DESSOLVE III, 1,398 patients undergoing percutaneous coronary intervention were randomized to the widely used Xience everolimus-eluting stent or to MiStent, a novel thin-strut stent with a polymer coating that is quickly absorbed after delivering microcrystalline sirolimus into the vessel wall for prolonged release at a near-linear rate.
At an interim analysis at 12 months of follow-up, the primary endpoint – a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization – had occurred in 5.8% of the MiStent group and 6.5% of Xience recipients in the study, which was designed as a noninferiority trial, reported Robbert J. de Winter, MD, professor of clinical cardiology at the Academic Medical Center in Amsterdam.
“The data support the hypothesis that long-term cytostatic inhibition of early neointima could prevent the late neointimal growth seen at medium and long term with conventional drug-eluting stents,” he said.
MiStent is designed to overcome a shortcoming of conventional drug-eluting stents: namely, their durable polymer coating sticks around after the cytostatic drug is finished being released. It is believed that this residual polymer, which may not disappear for 6-9 months, induces inflammation in the vessel wall, eventually leading to intimal growth, restenosis, and new atherosclerosis.
“The unique feature of the MiStent is that the polymer is bioabsorbable and is fully absorbed at 3 months, whereas the drug is present in the vessel wall out to 9 months, well after the coating has disappeared. So in theory you would expect that any inflammatory response caused by the polymer coating will be counteracted by the drug. This was seen in animal models. And in the DESSOLVE I and II studies, angiographic follow-up showed that late luminal loss was flat after 6 months, in contrast to other drug-eluting stents, which show accrual of late neointimal growth after 6 months to a year,” according to the cardiologist.
DESSOLVE III is planned as a 3-year study. Already by 6 months the curves for target lesion revascularization started to separate, with a 12-month rate of 2.6% in the MiStent group versus 3.8% for Xience. And while this difference is not yet statistically significant, Dr. de Winter and his coinvestigators expect that by 3 years the separation will have grown to the point that the difference becomes statistically significant and clinically meaningful.
The MiStent platform is composed of a cobalt/chromium alloy. The stent strut thickness is only 64 microns, in contrast to 81 microns for the Xience stent. Thinner stent struts have previously been shown to be less injurious to the vessel wall.
DESSOLVE III is an all-comers trial conducted at 20 sites in four European countries. Participants had to have a reference vessel diameter of 2.5-3.5 mm. Roughly 60% of patients had an acute coronary syndrome as their indication for PCI. The study population included, among others, patients with left main coronary artery lesions, restenotic lesions, and failed saphenous vein grafts. Dual-antiplatelet therapy was given for 6 months in patients with stable angina and 12 months for those with ACS, in accordance with European Society of Cardiology guidelines.
Discussant Robert A. Byrne, MD, of the German Heart Center in Munich, declared: “For me, this is a potentially interesting device. It’s the only device where we have a drug elution that’s more prolonged than the polymer, and this does offer the potential for later benefit.”
Dr. Byrne was a member of a European Commission–backed task force that developed European regulatory guidance for the evaluation of new coronary stents. “This MiStent trial program ticks off a lot of boxes: We had a successful first human use study, then we had a modest-size angiographic endpoint study where the late lumen loss looked good, and now we have a clinical endpoint study. This is what we want to see in the regulatory space.”
Another discussant, Chaim Lotan, MD, pronounced the MiStent “definitely another good stent on the shelf.”
It’s impossible to say whether the excellent 1-year outcomes seen with MiStent in DESSOLVE III were due to the prolonged-release microcrystalline sirolimus, the ultrathin stent struts, or both. In any case, the major adverse cardiovascular event rates seen in DESSOLVE III are so low by historical standards that it will become extremely difficult to show superiority for one contemporary drug-eluting stent over another, predicted Dr. Lotan of Hadassah Medical Center in Jerusalem.
Dr. de Winter concurred.
“I think we can now say that the benchmark for present day drug-eluting stents is a target lesion failure rate of about 6% at 12 months and a stent thrombosis rate below 1% at 12 months. It’s going to be increasingly more difficult to improve on that,” he said.
The MiStent, manufactured by Micell Technologies, is commercially available in Europe but investigational in the United States.
DESSOLVE III was sponsored by the European Cardiovascular Research Institute and supported by grants from Micell Technologies and Stentys.
Dr. de Winter reported receiving research grants from OrbusNeich, Abbott Vascular, AstraZeneca, Stentys, and Tryton.
PARIS – A unique drug-eluting coronary stent showed positive interim results in the DESSOLVE III trial presented at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
In DESSOLVE III, 1,398 patients undergoing percutaneous coronary intervention were randomized to the widely used Xience everolimus-eluting stent or to MiStent, a novel thin-strut stent with a polymer coating that is quickly absorbed after delivering microcrystalline sirolimus into the vessel wall for prolonged release at a near-linear rate.
At an interim analysis at 12 months of follow-up, the primary endpoint – a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization – had occurred in 5.8% of the MiStent group and 6.5% of Xience recipients in the study, which was designed as a noninferiority trial, reported Robbert J. de Winter, MD, professor of clinical cardiology at the Academic Medical Center in Amsterdam.
“The data support the hypothesis that long-term cytostatic inhibition of early neointima could prevent the late neointimal growth seen at medium and long term with conventional drug-eluting stents,” he said.
MiStent is designed to overcome a shortcoming of conventional drug-eluting stents: namely, their durable polymer coating sticks around after the cytostatic drug is finished being released. It is believed that this residual polymer, which may not disappear for 6-9 months, induces inflammation in the vessel wall, eventually leading to intimal growth, restenosis, and new atherosclerosis.
“The unique feature of the MiStent is that the polymer is bioabsorbable and is fully absorbed at 3 months, whereas the drug is present in the vessel wall out to 9 months, well after the coating has disappeared. So in theory you would expect that any inflammatory response caused by the polymer coating will be counteracted by the drug. This was seen in animal models. And in the DESSOLVE I and II studies, angiographic follow-up showed that late luminal loss was flat after 6 months, in contrast to other drug-eluting stents, which show accrual of late neointimal growth after 6 months to a year,” according to the cardiologist.
DESSOLVE III is planned as a 3-year study. Already by 6 months the curves for target lesion revascularization started to separate, with a 12-month rate of 2.6% in the MiStent group versus 3.8% for Xience. And while this difference is not yet statistically significant, Dr. de Winter and his coinvestigators expect that by 3 years the separation will have grown to the point that the difference becomes statistically significant and clinically meaningful.
The MiStent platform is composed of a cobalt/chromium alloy. The stent strut thickness is only 64 microns, in contrast to 81 microns for the Xience stent. Thinner stent struts have previously been shown to be less injurious to the vessel wall.
DESSOLVE III is an all-comers trial conducted at 20 sites in four European countries. Participants had to have a reference vessel diameter of 2.5-3.5 mm. Roughly 60% of patients had an acute coronary syndrome as their indication for PCI. The study population included, among others, patients with left main coronary artery lesions, restenotic lesions, and failed saphenous vein grafts. Dual-antiplatelet therapy was given for 6 months in patients with stable angina and 12 months for those with ACS, in accordance with European Society of Cardiology guidelines.
Discussant Robert A. Byrne, MD, of the German Heart Center in Munich, declared: “For me, this is a potentially interesting device. It’s the only device where we have a drug elution that’s more prolonged than the polymer, and this does offer the potential for later benefit.”
Dr. Byrne was a member of a European Commission–backed task force that developed European regulatory guidance for the evaluation of new coronary stents. “This MiStent trial program ticks off a lot of boxes: We had a successful first human use study, then we had a modest-size angiographic endpoint study where the late lumen loss looked good, and now we have a clinical endpoint study. This is what we want to see in the regulatory space.”
Another discussant, Chaim Lotan, MD, pronounced the MiStent “definitely another good stent on the shelf.”
It’s impossible to say whether the excellent 1-year outcomes seen with MiStent in DESSOLVE III were due to the prolonged-release microcrystalline sirolimus, the ultrathin stent struts, or both. In any case, the major adverse cardiovascular event rates seen in DESSOLVE III are so low by historical standards that it will become extremely difficult to show superiority for one contemporary drug-eluting stent over another, predicted Dr. Lotan of Hadassah Medical Center in Jerusalem.
Dr. de Winter concurred.
“I think we can now say that the benchmark for present day drug-eluting stents is a target lesion failure rate of about 6% at 12 months and a stent thrombosis rate below 1% at 12 months. It’s going to be increasingly more difficult to improve on that,” he said.
The MiStent, manufactured by Micell Technologies, is commercially available in Europe but investigational in the United States.
DESSOLVE III was sponsored by the European Cardiovascular Research Institute and supported by grants from Micell Technologies and Stentys.
Dr. de Winter reported receiving research grants from OrbusNeich, Abbott Vascular, AstraZeneca, Stentys, and Tryton.
AT EUROPCR
Key clinical point:
Major finding: At an interim 12-month analysis, the composite rate of cardiac death, target vessel MI, and clinically indicated target lesion revascularization was 6.5% in recipients of a Xience everolimus-eluting coronary stent and 5.8% in those randomized to the novel MiStent.
Data source: DESSOLVE III, a prospective, randomized, international trial that randomized 1,398 real-world-type all-comers undergoing PCI to the Xience device or the MiStent.
Disclosures: DESSOLVE III was sponsored by the European Cardiovascular Research Institute and supported by grants from Micell Technologies and Stentys. The presenter reported receiving research grants from both companies.
Small brain infarcts’ cognitive impact equals that of large infarcts
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: A composite cognitive measure showed a decline of 1.5 standard deviations from baseline in patients with only infarct-like lesions, 1.6 standard deviations in those with large infarcts, and 2.5 standard deviations in subjects who had both lesions.
Data source: The ARIC substudy comprised 1,881 subjects followed for 20 years.
Disclosures: Dr. Windham had no financial disclosures.
Idarucizumab reversed dabigatran completely and rapidly in study
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
FROM 2017 ISTH CONGRESS
Key clinical point:
Major finding: Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group, 197 patients were able to undergo urgent procedures after a median of 1.6 hours.
Data source: A multicenter, prospective, open-label study of 503 patients (RE-VERSE AD).
Disclosures: Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, BMS/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
Amplatzer devices outperform oral anticoagulation in atrial fib
PARIS – Percutaneous left atrial appendage closure with an Amplatzer device in patients with nonvalvular atrial fibrillation was associated with significantly lower rates of all-cause and cardiovascular mortality, compared with oral anticoagulation, in a large propensity score–matched observational registry study.
Left atrial appendage closure (LAAC) also bested oral anticoagulation (OAC) with warfarin or a novel oral anticoagulant (NOAC) in terms of net clinical benefit on the basis of the device therapy’s greater protection against stroke and systemic embolism coupled with a trend, albeit not statistically significant, for fewer bleeding events, Steffen Gloekler, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The Watchman LAAC device, commercially available both in Europe and the United States, has previously been shown to be superior to OAC in terms of efficacy and noninferior regarding safety. But there have been no randomized trials of an Amplatzer device versus OAC. This lack of data was the impetus for Dr. Gloekler and his coinvestigators to create a meticulously propensity-matched observational registry.
Five hundred consecutive patients with AF who received an Amplatzer Cardiac Plug or its second-generation version, the Amplatzer Amulet, during 2009-2014 were tightly matched to an equal number of AF patients on OAC based on age, sex, body mass index, left ventricular ejection fraction, renal function, coronary artery disease status, hemoglobin level, CHA2DS2-VASc score, and HAS-BLED score. During a mean 2.7 years, or 2,645 patient-years, of follow-up, the composite primary efficacy endpoint, composed of stroke, systemic embolism, and cardiovascular or unexplained death occurred in 5.6% of the LAAC group, compared with 7.8% of controls in the OAC arm, for a statistically significant 30% relative risk reduction. Disabling stroke occurred in 0.7% of Amplatzer patients versus 1.5% of controls. The ischemic stroke rate was 1.5% in the device therapy group and 2% in the OAC arm.
All-cause mortality occurred in 8.3% of Amplatzer patients and 11.6% of the OAC group, for a 28% relative risk reduction. The cardiovascular death rate was 4% in the Amplatzer group, compared with 6.5% of controls, for a 36% risk reduction.
The composite safety endpoint, comprising all major procedural adverse events and major or life-threatening bleeding during follow-up, occurred in 3.6% of the Amplatzer group and 4.6% of the OAC group, for a 20% relative risk reduction that is not significant at this point because of the low number of events. Major, life-threatening, or fatal bleeding occurred in 2% of Amplatzer recipients versus 5.5% of controls, added Dr. Gloekler of University Hospital in Bern, Switzerland.
The net clinical benefit, a composite of death, bleeding, or stroke, occurred in 8.1% of the Amplatzer group, compared with 10.9% of controls, for a significant 24% reduction in relative risk in favor of device therapy.
Of note, at 2.7 years of follow-up only 55% of the OAC group were still taking an anticoagulant: 38% of the original 500 patients were on warfarin, and 17% were taking a NOAC. At that point, 8% of the Amplatzer group were on any anticoagulation therapy.
Discussion of the study focused on that low rate of medication adherence in the OAC arm. Dr. Gloekler’s response was that, after looking at the literature, he was no longer surprised by the finding that only 55% of the control group were on OAC at follow-up.
“If you look in the literature, that’s exactly the real-world adherence for OACs. Even in all four certification trials for the NOACs, the rate of discontinuation was 30% after 2 years – and these were controlled studies. Ours was observational, and it depicts a good deal of the problem with any OAC in my eyes,” Dr. Gloekler said.
Patients on warfarin in the real-world Amplatzer registry study spent on average a mere 30% of time in the therapeutic international normalized ratio range of 2-3.
“That means 70% of the time patients are higher and have an increased bleeding risk or they are lower and don’t have adequate stroke protection,” he noted.
This prompted one observer to comment, “We either have to do a better job in our clinics with OAC or we have to occlude more appendages.”
A large pivotal U.S. trial aimed at winning FDA approval for the Amplatzer Amulet for LAAC is underway. Patients with AF are being randomized to the approved Watchman or investigational Amulet at roughly 100 U.S. and 50 foreign sites.
Dr. Gloekler reported receiving research funds for the registry from the Swiss Heart Foundation and Abbott.
PARIS – Percutaneous left atrial appendage closure with an Amplatzer device in patients with nonvalvular atrial fibrillation was associated with significantly lower rates of all-cause and cardiovascular mortality, compared with oral anticoagulation, in a large propensity score–matched observational registry study.
Left atrial appendage closure (LAAC) also bested oral anticoagulation (OAC) with warfarin or a novel oral anticoagulant (NOAC) in terms of net clinical benefit on the basis of the device therapy’s greater protection against stroke and systemic embolism coupled with a trend, albeit not statistically significant, for fewer bleeding events, Steffen Gloekler, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The Watchman LAAC device, commercially available both in Europe and the United States, has previously been shown to be superior to OAC in terms of efficacy and noninferior regarding safety. But there have been no randomized trials of an Amplatzer device versus OAC. This lack of data was the impetus for Dr. Gloekler and his coinvestigators to create a meticulously propensity-matched observational registry.
Five hundred consecutive patients with AF who received an Amplatzer Cardiac Plug or its second-generation version, the Amplatzer Amulet, during 2009-2014 were tightly matched to an equal number of AF patients on OAC based on age, sex, body mass index, left ventricular ejection fraction, renal function, coronary artery disease status, hemoglobin level, CHA2DS2-VASc score, and HAS-BLED score. During a mean 2.7 years, or 2,645 patient-years, of follow-up, the composite primary efficacy endpoint, composed of stroke, systemic embolism, and cardiovascular or unexplained death occurred in 5.6% of the LAAC group, compared with 7.8% of controls in the OAC arm, for a statistically significant 30% relative risk reduction. Disabling stroke occurred in 0.7% of Amplatzer patients versus 1.5% of controls. The ischemic stroke rate was 1.5% in the device therapy group and 2% in the OAC arm.
All-cause mortality occurred in 8.3% of Amplatzer patients and 11.6% of the OAC group, for a 28% relative risk reduction. The cardiovascular death rate was 4% in the Amplatzer group, compared with 6.5% of controls, for a 36% risk reduction.
The composite safety endpoint, comprising all major procedural adverse events and major or life-threatening bleeding during follow-up, occurred in 3.6% of the Amplatzer group and 4.6% of the OAC group, for a 20% relative risk reduction that is not significant at this point because of the low number of events. Major, life-threatening, or fatal bleeding occurred in 2% of Amplatzer recipients versus 5.5% of controls, added Dr. Gloekler of University Hospital in Bern, Switzerland.
The net clinical benefit, a composite of death, bleeding, or stroke, occurred in 8.1% of the Amplatzer group, compared with 10.9% of controls, for a significant 24% reduction in relative risk in favor of device therapy.
Of note, at 2.7 years of follow-up only 55% of the OAC group were still taking an anticoagulant: 38% of the original 500 patients were on warfarin, and 17% were taking a NOAC. At that point, 8% of the Amplatzer group were on any anticoagulation therapy.
Discussion of the study focused on that low rate of medication adherence in the OAC arm. Dr. Gloekler’s response was that, after looking at the literature, he was no longer surprised by the finding that only 55% of the control group were on OAC at follow-up.
“If you look in the literature, that’s exactly the real-world adherence for OACs. Even in all four certification trials for the NOACs, the rate of discontinuation was 30% after 2 years – and these were controlled studies. Ours was observational, and it depicts a good deal of the problem with any OAC in my eyes,” Dr. Gloekler said.
Patients on warfarin in the real-world Amplatzer registry study spent on average a mere 30% of time in the therapeutic international normalized ratio range of 2-3.
“That means 70% of the time patients are higher and have an increased bleeding risk or they are lower and don’t have adequate stroke protection,” he noted.
This prompted one observer to comment, “We either have to do a better job in our clinics with OAC or we have to occlude more appendages.”
A large pivotal U.S. trial aimed at winning FDA approval for the Amplatzer Amulet for LAAC is underway. Patients with AF are being randomized to the approved Watchman or investigational Amulet at roughly 100 U.S. and 50 foreign sites.
Dr. Gloekler reported receiving research funds for the registry from the Swiss Heart Foundation and Abbott.
PARIS – Percutaneous left atrial appendage closure with an Amplatzer device in patients with nonvalvular atrial fibrillation was associated with significantly lower rates of all-cause and cardiovascular mortality, compared with oral anticoagulation, in a large propensity score–matched observational registry study.
Left atrial appendage closure (LAAC) also bested oral anticoagulation (OAC) with warfarin or a novel oral anticoagulant (NOAC) in terms of net clinical benefit on the basis of the device therapy’s greater protection against stroke and systemic embolism coupled with a trend, albeit not statistically significant, for fewer bleeding events, Steffen Gloekler, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The Watchman LAAC device, commercially available both in Europe and the United States, has previously been shown to be superior to OAC in terms of efficacy and noninferior regarding safety. But there have been no randomized trials of an Amplatzer device versus OAC. This lack of data was the impetus for Dr. Gloekler and his coinvestigators to create a meticulously propensity-matched observational registry.
Five hundred consecutive patients with AF who received an Amplatzer Cardiac Plug or its second-generation version, the Amplatzer Amulet, during 2009-2014 were tightly matched to an equal number of AF patients on OAC based on age, sex, body mass index, left ventricular ejection fraction, renal function, coronary artery disease status, hemoglobin level, CHA2DS2-VASc score, and HAS-BLED score. During a mean 2.7 years, or 2,645 patient-years, of follow-up, the composite primary efficacy endpoint, composed of stroke, systemic embolism, and cardiovascular or unexplained death occurred in 5.6% of the LAAC group, compared with 7.8% of controls in the OAC arm, for a statistically significant 30% relative risk reduction. Disabling stroke occurred in 0.7% of Amplatzer patients versus 1.5% of controls. The ischemic stroke rate was 1.5% in the device therapy group and 2% in the OAC arm.
All-cause mortality occurred in 8.3% of Amplatzer patients and 11.6% of the OAC group, for a 28% relative risk reduction. The cardiovascular death rate was 4% in the Amplatzer group, compared with 6.5% of controls, for a 36% risk reduction.
The composite safety endpoint, comprising all major procedural adverse events and major or life-threatening bleeding during follow-up, occurred in 3.6% of the Amplatzer group and 4.6% of the OAC group, for a 20% relative risk reduction that is not significant at this point because of the low number of events. Major, life-threatening, or fatal bleeding occurred in 2% of Amplatzer recipients versus 5.5% of controls, added Dr. Gloekler of University Hospital in Bern, Switzerland.
The net clinical benefit, a composite of death, bleeding, or stroke, occurred in 8.1% of the Amplatzer group, compared with 10.9% of controls, for a significant 24% reduction in relative risk in favor of device therapy.
Of note, at 2.7 years of follow-up only 55% of the OAC group were still taking an anticoagulant: 38% of the original 500 patients were on warfarin, and 17% were taking a NOAC. At that point, 8% of the Amplatzer group were on any anticoagulation therapy.
Discussion of the study focused on that low rate of medication adherence in the OAC arm. Dr. Gloekler’s response was that, after looking at the literature, he was no longer surprised by the finding that only 55% of the control group were on OAC at follow-up.
“If you look in the literature, that’s exactly the real-world adherence for OACs. Even in all four certification trials for the NOACs, the rate of discontinuation was 30% after 2 years – and these were controlled studies. Ours was observational, and it depicts a good deal of the problem with any OAC in my eyes,” Dr. Gloekler said.
Patients on warfarin in the real-world Amplatzer registry study spent on average a mere 30% of time in the therapeutic international normalized ratio range of 2-3.
“That means 70% of the time patients are higher and have an increased bleeding risk or they are lower and don’t have adequate stroke protection,” he noted.
This prompted one observer to comment, “We either have to do a better job in our clinics with OAC or we have to occlude more appendages.”
A large pivotal U.S. trial aimed at winning FDA approval for the Amplatzer Amulet for LAAC is underway. Patients with AF are being randomized to the approved Watchman or investigational Amulet at roughly 100 U.S. and 50 foreign sites.
Dr. Gloekler reported receiving research funds for the registry from the Swiss Heart Foundation and Abbott.
AT EUROPCR
Key clinical point:
Major finding: The primary composite efficacy endpoint of stroke, systemic embolism, or cardiovascular or unexplained death during a mean 2.7 years of follow-up occurred in 5.6% of Amplatzer device recipients, a 30% reduction, compared with the 7.8% rate in the oral anticoagulation group.
Data source: This observational registry included 500 patients with atrial fibrillation who received an Amplatzer left atrial appendage closure device and an equal number of carefully matched AF patients on oral anticoagulation.
Disclosures: The study presenter reported receiving research funds for the registry from the Swiss Heart Foundation and Abbott.
VIDEO: Meta-analysis favors anticoagulation for patients with cirrhosis and portal vein thrombosis
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Anticoagulation produced favorable outcomes with no increase in bleeding risk in patients with cirrhosis and portal vein thrombosis.
Major finding: Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001); rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group.
Data source: A systematic review and meta-analysis of eight studies of 353 patients with cirrhosis and portal vein thrombosis.
Disclosures: The reviewers reported having no funding sources or conflicts of interest.
Herpes zoster raises risk of stroke, MI
Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.
In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.
The incidence of stroke was 1.34 per 1,000 person-years higher among patients with the infection than among those without it. Similarly, the incidence of MI was 0.80 per 1,000 person-years higher among patients with the infection than among those without it. The risks of both stroke and MI were highest during the first year after herpes onset and decreased over time. In contrast, the risks of stroke and MI were evenly distributed over time in the control group, the investigators said in a letter to the editor (J Am Coll Cardiol. 2017;70[2]:293-300). Several possible reasons have been proposed to explain a causal association between this infection and cardiovascular disease. Herpes zoster is “the only virus for which there is clear evidence of viral DNA and antigen in areas of ischemia or infarction in cerebral arteries,” Dr. Kim and associates noted.
Viral replication adjacent to a cerebral or cardiac artery could cause inflammation of the vessel, followed by subsequent thrombosis and rupture. Or, repeated subclinical reactivation of the virus could weaken the arteries. It is also possible that herpes zoster reactivation alters patients’ immunologic status, making them vulnerable to cerebrovascular or cardiovascular events, the investigators said.
This study was supported by the Korea Health Technology Research and Development Project, the Korea Health Industry Development Institute, and the Republic of Korea Ministry of Health & Welfare. Dr. Kim and associates reported having no relevant financial disclosures.
Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.
In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.
The incidence of stroke was 1.34 per 1,000 person-years higher among patients with the infection than among those without it. Similarly, the incidence of MI was 0.80 per 1,000 person-years higher among patients with the infection than among those without it. The risks of both stroke and MI were highest during the first year after herpes onset and decreased over time. In contrast, the risks of stroke and MI were evenly distributed over time in the control group, the investigators said in a letter to the editor (J Am Coll Cardiol. 2017;70[2]:293-300). Several possible reasons have been proposed to explain a causal association between this infection and cardiovascular disease. Herpes zoster is “the only virus for which there is clear evidence of viral DNA and antigen in areas of ischemia or infarction in cerebral arteries,” Dr. Kim and associates noted.
Viral replication adjacent to a cerebral or cardiac artery could cause inflammation of the vessel, followed by subsequent thrombosis and rupture. Or, repeated subclinical reactivation of the virus could weaken the arteries. It is also possible that herpes zoster reactivation alters patients’ immunologic status, making them vulnerable to cerebrovascular or cardiovascular events, the investigators said.
This study was supported by the Korea Health Technology Research and Development Project, the Korea Health Industry Development Institute, and the Republic of Korea Ministry of Health & Welfare. Dr. Kim and associates reported having no relevant financial disclosures.
Herpes zoster infection raised the risk of stroke by 35% and of myocardial infarction by 59%, in a South Korean nationwide study.
In addition, the risks of stroke and MI were highest in the first year following herpes zoster infection and decreased over time, said Min-Chul Kim, MD, the University of Ulsan, Seoul, South Korea, and associates.
The incidence of stroke was 1.34 per 1,000 person-years higher among patients with the infection than among those without it. Similarly, the incidence of MI was 0.80 per 1,000 person-years higher among patients with the infection than among those without it. The risks of both stroke and MI were highest during the first year after herpes onset and decreased over time. In contrast, the risks of stroke and MI were evenly distributed over time in the control group, the investigators said in a letter to the editor (J Am Coll Cardiol. 2017;70[2]:293-300). Several possible reasons have been proposed to explain a causal association between this infection and cardiovascular disease. Herpes zoster is “the only virus for which there is clear evidence of viral DNA and antigen in areas of ischemia or infarction in cerebral arteries,” Dr. Kim and associates noted.
Viral replication adjacent to a cerebral or cardiac artery could cause inflammation of the vessel, followed by subsequent thrombosis and rupture. Or, repeated subclinical reactivation of the virus could weaken the arteries. It is also possible that herpes zoster reactivation alters patients’ immunologic status, making them vulnerable to cerebrovascular or cardiovascular events, the investigators said.
This study was supported by the Korea Health Technology Research and Development Project, the Korea Health Industry Development Institute, and the Republic of Korea Ministry of Health & Welfare. Dr. Kim and associates reported having no relevant financial disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Herpes zoster infection raised the risk of stroke by 35% and of MI by 59% in a nationwide study in South Korea.
Major finding: The incidence of stroke was 1.34 per 1,000 person-years higher among patients with the infection than among those without it, and the incidence of MI was 0.80 per 1,000 person-years higher.
Data source: A cohort study of CV risk in 519,880 adults in South Korea.
Disclosures: This study was supported by the Korea Health Technology Research and Development Project, the Korea Health Industry Development Institute, and the Republic of Korea Ministry of Health & Welfare. Dr. Kim and associates reported having no relevant financial disclosures.