ACG: American College of Gastroenterology

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

 

AGA Resource
AGA offers information for your patients about constipation at http://www.gastro.org/patient-care/conditions-diseases/constipation.

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

 

AGA Resource
AGA offers information for your patients about constipation at http://www.gastro.org/patient-care/conditions-diseases/constipation.

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

 

AGA Resource
AGA offers information for your patients about constipation at http://www.gastro.org/patient-care/conditions-diseases/constipation.

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

[email protected]

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

[email protected]

 

LAS VEGAS – Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.

The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.

Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).

“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.

The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.

The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.

About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.

The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (P less than .001 for both comparisons).

Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.

Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.

“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.

Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.

Dr. Rao is a member of an advisory committee for Forest Laboratories, Hollister, In Control Medical, Ironwood, Sucampo, and Vibrant. Dr. Chey is a consultant for Ironwood and Synergy.

[email protected]

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.