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Novel anticoagulants increase GI bleeds in elderly
PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).
The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.
“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.
The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.
In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.
However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.
By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.
These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.
“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.
Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.
“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”
Dr. Abraham had no financial disclosures.
PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).
The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.
“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.
The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.
In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.
However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.
By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.
These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.
“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.
Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.
“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”
Dr. Abraham had no financial disclosures.
PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).
The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.
“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.
The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.
In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.
However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.
By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.
These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.
“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.
Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.
“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”
Dr. Abraham had no financial disclosures.
AT THE ANNUAL SCIENTIFIC MEETING AND POSTGRADUATE COURSE OF THE AMERICAN COLLEGE OF GASTROENTEROLOGY
<p><b>Key clinical point</b>: The novel oral anticoagulants dabigatran and rivaroxaban were associated with an increased risk of GI bleeding in elderly patients, compared with warfarin, in data drawn from a real-world setting.
</p><p><b>Major finding: </b>When compared with warfarin in atrial fibrillation, the risk of upper and lower GI bleeding is nearly 2.5 times greater on dabigatran and 3 times greater on rivaroxaban at age 75 years.
</p><p><b>Data source:</b> A retrospective, propensity-matched study.
</p><p><b>Disclosures:</b> Dr. Abraham had no financial disclosures.</p>
Lynch syndrome screening underperformed in high-risk patients
PHILADELPHIA– Despite evidence that screening reduces morbidity and mortality, even patients at high risk for Lynch syndrome (LS) are not being routinely evaluated, according to a comprehensive survey undertaken from a cancer registry and presented at the American College of Gastroenterology (ACG).
The survey, funded by the Centers for Disease Control and Prevention and undertaken in Louisiana, found that only 23% of patients who developed colorectal cancer (CRC) before the age of 50 years underwent even the first step in screening. The figure should be 100%, reported Dr. Jordan J. Karlitz, director, GI Hereditary Cancer and Genetics Program, Tulane University, New Orleans.
In addition, the majority of those who were screened were evaluated on the basis of tissue specimens taken at the time of cancer resection rather than at the initial colonoscopy. This is important because the presence of LS changes management, particularly the extent of resection.
“These data suggest that more effective protocols need to be put in place for ensuring that patients at risk are screened preoperatively using a time-efficient, multidisciplinary approach,” Dr. Karlitz reported.
The study was conducted in the context of recently revised guidelines, such as those from the National Comprehensive Cancer Network, that now recommend screening for LS in patients at any age with CRC.
“If the indications were being expanded, we wanted to know how well we were doing in those we already know are at high risk,” Dr. Karlitz said in an interview.
The answer was not very well. There were 274 patients under the age of 50 years found among a total of 2,427 CRC patients in the Louisiana Tumor Registry Comparative Effectiveness Research Project. In this group, microsatellite instability (MSI) analysis or immunohistochemistry (IHC) assays, which are the first steps in screening, had been performed in as few as 6% of young CRC patients in rural hospitals. Comprehensive tertiary care centers did better, but those rates only climbed to 40%.
Of those tested, abnormal MSI or IHC were seen in 20%, emphasizing that the yield is high in this population. Although confirmation of LS requires further germline genetic studies, the first step of MSI or IHC screening is critical.
The fact that screening for many patients was undertaken only after cancer resection is another worrisome finding, according to Dr. Karlitz, suggesting “a problem in the process.”
Asked for a comment, Dr. Dennis J. Ahnen, professor of medicine, University of Colorado, Denver, agreed. He suggested that both the low rate of screening for LS in a high-risk population and the failure to conduct the screening from tissue obtained at the initial colonoscopy suggest a need for protocols that will expedite appropriate intervention.
“The screening for Lynch syndrome has to be done at the time of diagnosis to ensure that these patients are managed optimally,” Dr. Ahnen suggested. “We need to perform MSI or IHC and the genetic testing prior to surgery.”
According to Dr. Karlitz, the best approach may be the development of protocols involving a multidisciplinary team so that the steps to screening, diagnosis, and patient management are well outlined.
“Improving our ability to screen for Lynch syndrome is not only important for the patient with CRC but for counseling family members who may also be affected,” Dr. Karlitz suggested. “This is a serious issue, because we know that missed Lynch syndrome is associated with an increased morbidity and mortality.”
PHILADELPHIA– Despite evidence that screening reduces morbidity and mortality, even patients at high risk for Lynch syndrome (LS) are not being routinely evaluated, according to a comprehensive survey undertaken from a cancer registry and presented at the American College of Gastroenterology (ACG).
The survey, funded by the Centers for Disease Control and Prevention and undertaken in Louisiana, found that only 23% of patients who developed colorectal cancer (CRC) before the age of 50 years underwent even the first step in screening. The figure should be 100%, reported Dr. Jordan J. Karlitz, director, GI Hereditary Cancer and Genetics Program, Tulane University, New Orleans.
In addition, the majority of those who were screened were evaluated on the basis of tissue specimens taken at the time of cancer resection rather than at the initial colonoscopy. This is important because the presence of LS changes management, particularly the extent of resection.
“These data suggest that more effective protocols need to be put in place for ensuring that patients at risk are screened preoperatively using a time-efficient, multidisciplinary approach,” Dr. Karlitz reported.
The study was conducted in the context of recently revised guidelines, such as those from the National Comprehensive Cancer Network, that now recommend screening for LS in patients at any age with CRC.
“If the indications were being expanded, we wanted to know how well we were doing in those we already know are at high risk,” Dr. Karlitz said in an interview.
The answer was not very well. There were 274 patients under the age of 50 years found among a total of 2,427 CRC patients in the Louisiana Tumor Registry Comparative Effectiveness Research Project. In this group, microsatellite instability (MSI) analysis or immunohistochemistry (IHC) assays, which are the first steps in screening, had been performed in as few as 6% of young CRC patients in rural hospitals. Comprehensive tertiary care centers did better, but those rates only climbed to 40%.
Of those tested, abnormal MSI or IHC were seen in 20%, emphasizing that the yield is high in this population. Although confirmation of LS requires further germline genetic studies, the first step of MSI or IHC screening is critical.
The fact that screening for many patients was undertaken only after cancer resection is another worrisome finding, according to Dr. Karlitz, suggesting “a problem in the process.”
Asked for a comment, Dr. Dennis J. Ahnen, professor of medicine, University of Colorado, Denver, agreed. He suggested that both the low rate of screening for LS in a high-risk population and the failure to conduct the screening from tissue obtained at the initial colonoscopy suggest a need for protocols that will expedite appropriate intervention.
“The screening for Lynch syndrome has to be done at the time of diagnosis to ensure that these patients are managed optimally,” Dr. Ahnen suggested. “We need to perform MSI or IHC and the genetic testing prior to surgery.”
According to Dr. Karlitz, the best approach may be the development of protocols involving a multidisciplinary team so that the steps to screening, diagnosis, and patient management are well outlined.
“Improving our ability to screen for Lynch syndrome is not only important for the patient with CRC but for counseling family members who may also be affected,” Dr. Karlitz suggested. “This is a serious issue, because we know that missed Lynch syndrome is associated with an increased morbidity and mortality.”
PHILADELPHIA– Despite evidence that screening reduces morbidity and mortality, even patients at high risk for Lynch syndrome (LS) are not being routinely evaluated, according to a comprehensive survey undertaken from a cancer registry and presented at the American College of Gastroenterology (ACG).
The survey, funded by the Centers for Disease Control and Prevention and undertaken in Louisiana, found that only 23% of patients who developed colorectal cancer (CRC) before the age of 50 years underwent even the first step in screening. The figure should be 100%, reported Dr. Jordan J. Karlitz, director, GI Hereditary Cancer and Genetics Program, Tulane University, New Orleans.
In addition, the majority of those who were screened were evaluated on the basis of tissue specimens taken at the time of cancer resection rather than at the initial colonoscopy. This is important because the presence of LS changes management, particularly the extent of resection.
“These data suggest that more effective protocols need to be put in place for ensuring that patients at risk are screened preoperatively using a time-efficient, multidisciplinary approach,” Dr. Karlitz reported.
The study was conducted in the context of recently revised guidelines, such as those from the National Comprehensive Cancer Network, that now recommend screening for LS in patients at any age with CRC.
“If the indications were being expanded, we wanted to know how well we were doing in those we already know are at high risk,” Dr. Karlitz said in an interview.
The answer was not very well. There were 274 patients under the age of 50 years found among a total of 2,427 CRC patients in the Louisiana Tumor Registry Comparative Effectiveness Research Project. In this group, microsatellite instability (MSI) analysis or immunohistochemistry (IHC) assays, which are the first steps in screening, had been performed in as few as 6% of young CRC patients in rural hospitals. Comprehensive tertiary care centers did better, but those rates only climbed to 40%.
Of those tested, abnormal MSI or IHC were seen in 20%, emphasizing that the yield is high in this population. Although confirmation of LS requires further germline genetic studies, the first step of MSI or IHC screening is critical.
The fact that screening for many patients was undertaken only after cancer resection is another worrisome finding, according to Dr. Karlitz, suggesting “a problem in the process.”
Asked for a comment, Dr. Dennis J. Ahnen, professor of medicine, University of Colorado, Denver, agreed. He suggested that both the low rate of screening for LS in a high-risk population and the failure to conduct the screening from tissue obtained at the initial colonoscopy suggest a need for protocols that will expedite appropriate intervention.
“The screening for Lynch syndrome has to be done at the time of diagnosis to ensure that these patients are managed optimally,” Dr. Ahnen suggested. “We need to perform MSI or IHC and the genetic testing prior to surgery.”
According to Dr. Karlitz, the best approach may be the development of protocols involving a multidisciplinary team so that the steps to screening, diagnosis, and patient management are well outlined.
“Improving our ability to screen for Lynch syndrome is not only important for the patient with CRC but for counseling family members who may also be affected,” Dr. Karlitz suggested. “This is a serious issue, because we know that missed Lynch syndrome is associated with an increased morbidity and mortality.”
ANNUAL SCIENTIFIC MEETING AND POSTGRADUATE COURSE OF THE AMERICAN COLLEGE OF GASTROENTEROLOGY
<p><b>Key clinical point</b>: Lynch syndrome screening, increasingly recommended in all colorectal cancer (CRC) patients, appears to be infrequently performed even in relatively young patients at highest risk.
</p><p><b>Major finding:</b> In a statewide survey, the first step in screening for Lynch syndrome with microsatellite instability testing or immunohistochemistry analysis was performed in just 23%.
</p><p><b>Data source:</b> Retrospective centralized review of registry data.
</p><p><b>Disclosures:</b> Dr. Jordan Karlitz reported no potential financial conflicts of interest.</p>
