Thrombosis

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

Photo from Bayer

Health Canada has approved Jivi^® (antihemophilic factor [recombinant, B-domain deleted, PEGylated]) for use in patients with hemophilia A.

Jivi (formerly BAY94-9027) is a DNA-derived, factor VIII concentrate developed by Bayer.

Health Canada has approved Jivi for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in previously treated hemophilia A patients age 12 and older.

Jivi is also approved for the control and prevention of episodic bleeding and for perioperative management of bleeding.

The recommended initial dosing for Jivi as prophylaxis is twice weekly, with the ability to dose every 5 days and further adjust dosing based on bleeding episodes.

Health Canada’s approval of Jivi is based on the PROTECT VIII trial. Results from this trial are available in the U.S. prescribing information for Jivi.

PROTECT VIII enrolled previously treated adults and adolescents (ages 12 to 65) with severe hemophilia A.

In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, Jivi was used for perioperative management of bleeding.

Efficacy

In part A, there were 132 patients in the intent‐to‐treat population—112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30–40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45–60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) was 4.1 for the patients who were treated twice weekly and were not eligible for randomization (n=13) and 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n=11).

The median ABR was 1.9 for patients who were randomized to treatment every 5 days (n=43) and 0.96 for patients who completed prophylaxis with dosing every 7 days (32/43).

The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group. Overall, 73.3% of responses to treatment were considered “excellent” or “good,” 23.3% were considered “moderate,” and 3.3% were considered “poor.”

There were 17 patients who underwent 20 major surgeries in part B or the extension study and 10 patients who underwent minor surgeries in part A. Jivi provided “good” or “excellent” hemostatic control during all surgeries.

Safety

Safety data are available for 148 patients age 12 and older.

Adverse events in these patients included abdominal pain (3%), nausea (5%), vomiting (3%), injection site reactions (1%), pyrexia (5%), hypersensitivity (2%), dizziness (2%), headache (14%), insomnia (3%), cough (7%), erythema (1%), pruritus (1%), rash (2%), and flushing (1%).

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.

Doug Brunk/MDedge News

“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”

In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”

In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.

Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).

“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”

She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.

ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.

Doug Brunk/MDedge News

“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”

In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”

In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.

Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).

“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”

She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.

ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.

Doug Brunk/MDedge News

“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”

In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”

In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.

Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).

“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”

She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.

MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.

Mitchel L. Zoler/MDedge News

Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.

“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).

“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”

Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS₂ score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA₂DS₂-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.

To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.

When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
 

[email protected]
 

Source: Hacke W et al. World Stroke Congress, Abstract.

MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.

Mitchel L. Zoler/MDedge News

Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.

“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).

“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”

Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS₂ score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA₂DS₂-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.

To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.

When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
 

[email protected]
 

Source: Hacke W et al. World Stroke Congress, Abstract.

MONTREAL – Stroke and transient ischemic attack, usually joined at the hip as related histories that each flag a similar need for anticoagulation may in fact not be nearly as equivalent as conventional wisdom says.

Mitchel L. Zoler/MDedge News

Analysis of 2-year follow-up data from the GARFIELD-AF registry of more than 52,000 patients with newly diagnosed atrial fibrillation (AF) showed that, while patients with a history of stroke had significantly elevated rates of both all-cause mortality and stroke, those with just a history of a transient ischemic attack (TIA) had mortality and stroke rates virtually identical to AF patients with no history of a cerebrovascular event.

“A history of TIA only is not a reliable predictor of an increased risk for events,” Werner Hacke, MD, said at the World Stroke Congress. “A history of TIA should be removed from scores estimating the risk for stroke and systemic embolism in AF patients,” said Dr. Hacke, professor and chairman of the department of neurology at the University of Heidelberg (Germany).

“The weak predictive power of a history of TIA is probably caused by the relatively low reliability of establishing the diagnosis of TIA,” especially when the diagnosis is made by someone who’s not a neurologist. “It’s a very fuzzy diagnosis,” even for a neurologist, and it consistently confounds other clinicians, he said in an interview. “I’d be really careful of deciding to anticoagulate a patient [with AF] based on a history of TIA.” In the GARFIELD-AF registry, “I’m convinced that most people with a history of TIA actually never had a TIA.”

Dr. Hacke has been unable to find a good explanation of why, years ago, TIAs began to get routinely lumped with stroke. “I asked all the old AF guys when did TIA start coming in and why, and none of them could remember,” he said. “At first, they talked about a history of ‘cerebrovascular events,’ but then that became stroke and TIA, and it was as if it was one word,” always said in the same breath. Both the CHADS₂ score (JAMA. 2001 Jun 13;285[22]:2864-70) and the CHA₂DS₂-VASc score (Chest. 2010 Feb;137[2]:263-72) make a history of stroke or TIA, as well as thromboembolism, coequal risk factors that count for 2 points when calculating the thrombotic risk score for a patient with AF.

To test whether this really made sense, Dr. Hacke and his associates decided to look at the separate consequences of a history of stroke only, compared with a history of a TIA only. They used data collected in GARFIELD-AF (Global Anticoagulant Registry in the Field), a multinational registry with 51,670 patients newly diagnosed with AF, followed for 2 years, and with complete information on their stroke and TIA history. This included 5,617 patients with a history of at least one diagnosed cerebrovascular event, including 3,362 diagnosed with stroke only, 1,788 diagnosed with TIA only, and the remaining patients diagnosed with both types of events.

When compared with AF patients without a history of any type of cerebrovascular event, those with a history of a stroke only had a statistically significant 29% increased rate of all-cause death and a 2.3-fold higher rate of stroke after adjustment for baseline demographic and clinical differences. In contrast, the patients with a history of TIA only had mortality and stroke rates during follow-up that did not differ significantly from the comparator group.
 

[email protected]
 

Source: Hacke W et al. World Stroke Congress, Abstract.

Image from Graham Beards

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to PRN1008 for the treatment of patients with immune thrombocytopenia (ITP).

PRN1008 is an oral, reversible, covalent Bruton’s tyrosine kinase (BTK) inhibitor being developed by Principia Biopharma, Inc.

Principia is conducting a phase 1/2 trial (NCT03395210) to evaluate the safety and efficacy of PRN1008 in patients with ITP.

Results of preclinical research with PRN1008 in ITP were presented at the 2017 ASH Annual Meeting.

There, researchers reported that PRN1008 significantly reduced platelet loss in a mouse model of ITP.

The team found the BTK inhibitor could diminish platelet loss in two ways:

• By reducing platelet destruction via inhibition of autoantibody/FcγR signaling in splenic macrophages
• By reducing autoantibody generation through inhibition of B-cell activation and maturation.

The researchers also assessed the effects of PRN1008 and ibrutinib on platelet function in samples from healthy volunteers and ITP patients.

Samples were treated with one of the two BTK inhibitors, and platelet aggregation was induced by platelet agonists.

Unlike ibrutinib, PRN1008 did not impact platelet aggregation in healthy volunteer or ITP patient samples.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Image from Graham Beards

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to PRN1008 for the treatment of patients with immune thrombocytopenia (ITP).

PRN1008 is an oral, reversible, covalent Bruton’s tyrosine kinase (BTK) inhibitor being developed by Principia Biopharma, Inc.

Principia is conducting a phase 1/2 trial (NCT03395210) to evaluate the safety and efficacy of PRN1008 in patients with ITP.

Results of preclinical research with PRN1008 in ITP were presented at the 2017 ASH Annual Meeting.

There, researchers reported that PRN1008 significantly reduced platelet loss in a mouse model of ITP.

The team found the BTK inhibitor could diminish platelet loss in two ways:

• By reducing platelet destruction via inhibition of autoantibody/FcγR signaling in splenic macrophages
• By reducing autoantibody generation through inhibition of B-cell activation and maturation.

The researchers also assessed the effects of PRN1008 and ibrutinib on platelet function in samples from healthy volunteers and ITP patients.

Samples were treated with one of the two BTK inhibitors, and platelet aggregation was induced by platelet agonists.

Unlike ibrutinib, PRN1008 did not impact platelet aggregation in healthy volunteer or ITP patient samples.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Image from Graham Beards

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to PRN1008 for the treatment of patients with immune thrombocytopenia (ITP).

PRN1008 is an oral, reversible, covalent Bruton’s tyrosine kinase (BTK) inhibitor being developed by Principia Biopharma, Inc.

Principia is conducting a phase 1/2 trial (NCT03395210) to evaluate the safety and efficacy of PRN1008 in patients with ITP.

Results of preclinical research with PRN1008 in ITP were presented at the 2017 ASH Annual Meeting.

There, researchers reported that PRN1008 significantly reduced platelet loss in a mouse model of ITP.

The team found the BTK inhibitor could diminish platelet loss in two ways:

• By reducing platelet destruction via inhibition of autoantibody/FcγR signaling in splenic macrophages
• By reducing autoantibody generation through inhibition of B-cell activation and maturation.

The researchers also assessed the effects of PRN1008 and ibrutinib on platelet function in samples from healthy volunteers and ITP patients.

Samples were treated with one of the two BTK inhibitors, and platelet aggregation was induced by platelet agonists.

Unlike ibrutinib, PRN1008 did not impact platelet aggregation in healthy volunteer or ITP patient samples.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

Photo by Bill Branson

The European Medicine’s Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended a change to the terms of the marketing authorization for the recombinant factor VIIa product eptacog alfa (NovoSeven).

The recommendation is to expand the approved use of eptacog alfa in patients with Glanzmann’s thrombasthenia.

Eptacog alfa is already approved by the European Commission (EC) for use in patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen who have past or present refractoriness to platelet transfusions.

Now, the CHMP has recommended expanding the use of eptacog alfa to include situations in which patients are not refractory to platelet transfusions but platelets are not readily available.

The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein. The EC usually makes a decision within 67 days of CHMP recommendations.

If the EC follows the CHMP’s recommendation for eptacog alfa, the product will be approved for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups:

• Patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda units
• Patients with congenital hemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration
• Patients with acquired hemophilia
• Patients with congenital FVII deficiency
• Patients with Glanzmann’s thrombasthenia with antibodies to glycoprotein IIb/IIIa and/or human leukocyte antigen and past or present refractoriness to platelet transfusions, or where platelets are not readily available.

MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.

Mitchel L. Zoler/MDedge News

The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).

The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.

In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.

“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).

Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”

Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.

“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.

POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.

[email protected]

SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.

MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.

Mitchel L. Zoler/MDedge News

The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).

The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.

In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.

“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).

Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”

Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.

“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.

POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.

[email protected]

SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.

MONTREAL – The optimal length for dual antiplatelet therapy in patients who have just had a mild stroke or transient ischemic attack is 21 days, a duration of combined treatment that maximized protection against major ischemic events while minimizing the extra risk for a major hemorrhage, according to a prespecified analysis of data from the POINT trial.

Mitchel L. Zoler/MDedge News

The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial randomized 4,881 patients with a very recent mild stroke or transient ischemic attack and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, dual antiplatelet therapy (DAPT) cut the incidence of a major ischemic event by a relative 25% but also more than doubled the rate of major hemorrhage (New Engl J Med. 2018 Jul 19;377[3]:215-25).

The new, prespecified analysis looked at outcomes on a week-by-week basis over the course of 90 days of treatment, and showed that during the first 21 days the rate of major ischemic events was 5.6% among patients on aspirin only and 3.6% among those on DAPT, a statistically significant 35% relative cut in these adverse outcomes by using DAPT, Jordan J. Elm, PhD, reported at the World Stroke Congress. During the subsequent 69 days on treatment, the incidence of major ischemic events was roughly 1% in both arms of the study, showing that after 3 weeks the incremental benefit from DAPT disappeared, said Dr. Elm, a biostatistician at the Medical University of South Carolina, Charleston.

In contrast, the doubled rate of major hemorrhages (mostly reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment, meaning that limiting DAPT to just 21 days could prevent many of the excess hemorrhages.

“These results suggest that limiting clopidogrel plus aspirin use to 21 days may maximize benefit and reduce risk,” Dr. Elm said, especially in light of the findings confirming the efficacy of 21 days of DAPT following a minor stroke or TIA that had been reported several years ago in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial (New Engl J Med. 2013 Jul 4;369[1]:11-9).

Although the new finding from the POINT results came in a secondary analysis, it’s statistically legitimate and should be taken into account when writing treatment guidelines, she said, emphasizing that “this is a very important analysis that is not just hypothesis generating.”

Another finding from the new analysis was that a large number of major ischemic events, and hence a large number of the events prevented by DAPT, occurred in the first 2 days following the index event, a finding made possible because the POINT investigators enrolled patients and started treatment within 12 hours of the qualifying events.

“It’s better to start treatment early,” Dr. Elm noted, but she also highlighted that major ischemic events continued to accumulate during days 3-21, suggesting that patients could still benefit from DAPT even if treatment did not start until 24 or 48 hours after their index event.

POINT received no commercial funding aside from study drugs supplied by Sanofi. Dr. Elm reported no disclosures.

[email protected]

SOURCE: Elm JJ et al. World Stroke Congress, Late-breaking session.