AVAHO

Theme
medstat_avaho
avaho
Main menu
AVAHO Main Menu
Unpublish
Negative Keywords Excluded Elements
header[@id='header']
div[contains(@class, 'header__large-screen')]
div[contains(@class, 'read-next-article')]
div[contains(@class, 'nav-primary')]
nav[contains(@class, 'nav-primary')]
section[contains(@class, 'footer-nav-section-wrapper')]
footer[@id='footer']
div[contains(@class, 'main-prefix')]
section[contains(@class, 'nav-hidden')]
div[contains(@class, 'ce-card-content')]
nav[contains(@class, 'nav-ce-stack')]
Altmetric
DSM Affiliated
Display in offset block
Enable Disqus
Display Author and Disclosure Link
Publication Type
Clinical
Slot System
Top 25
Disable Sticky Ads
Disable Ad Block Mitigation
Featured Buckets Admin
Show Ads on this Publication's Homepage
Consolidated Pub
Show Article Page Numbers on TOC
Use larger logo size
Off
publication_blueconic_enabled
Off
Show More Destinations Menu
Disable Adhesion on Publication
Off
Mobile Logo Image
Restore Menu Label on Mobile Navigation
Disable Facebook Pixel from Publication
Exclude this publication from publication selection on articles and quiz
Gating Strategy
First Page Free
Challenge Center
Disable Inline Native ads
Mobile Logo Media

Emergency Presentations for Vets with CRC Linked to Higher Mortality

Article Type
Changed
Thu, 01/23/2025 - 10:11

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

  •       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
  •       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
  •       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

  •      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
  •      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
  •      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

Publications
Topics
Sections

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

  •       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
  •       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
  •       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

  •      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
  •      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
  •      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

  •       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
  •       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
  •       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

  •      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
  •      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
  •      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Wed, 01/22/2025 - 14:11
Un-Gate On Date
Wed, 01/22/2025 - 14:11
Use ProPublica
CFC Schedule Remove Status
Wed, 01/22/2025 - 14:11
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Wed, 01/22/2025 - 14:11

FDA Approves Sotorasib + Panitumumab for mCRC

Article Type
Changed
Thu, 01/23/2025 - 10:14

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Wed, 01/22/2025 - 13:30
Un-Gate On Date
Wed, 01/22/2025 - 13:30
Use ProPublica
CFC Schedule Remove Status
Wed, 01/22/2025 - 13:30
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Wed, 01/22/2025 - 13:30

Physical Activity Before Cancer Diagnosis Linked to Lower Progression and Mortality Risk

Article Type
Changed
Tue, 01/21/2025 - 13:45

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

  • Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
  • The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
  • Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
  • Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
  • Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

  • Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
  • For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
  • At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
  • Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

  • Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
  • The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
  • Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
  • Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
  • Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

  • Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
  • For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
  • At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
  • Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

  • Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
  • The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
  • Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
  • Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
  • Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

  • Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
  • For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
  • At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
  • Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Tue, 01/21/2025 - 13:44
Un-Gate On Date
Tue, 01/21/2025 - 13:44
Use ProPublica
CFC Schedule Remove Status
Tue, 01/21/2025 - 13:44
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Tue, 01/21/2025 - 13:44

Lack of Chemoradiation Impact in Endometrial Cancer: The Need for Quicker Results in the Future

Article Type
Changed
Tue, 01/21/2025 - 09:22

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Tue, 01/21/2025 - 09:19
Un-Gate On Date
Tue, 01/21/2025 - 09:19
Use ProPublica
CFC Schedule Remove Status
Tue, 01/21/2025 - 09:19
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Tue, 01/21/2025 - 09:19

Agent Orange and Uranium Exposures Associated With Bladder Cancer Risk in Veterans

Article Type
Changed
Thu, 01/16/2025 - 12:39

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Publications
Topics
Sections

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Thu, 01/16/2025 - 12:08
Un-Gate On Date
Thu, 01/16/2025 - 12:08
Use ProPublica
CFC Schedule Remove Status
Thu, 01/16/2025 - 12:08
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Thu, 01/16/2025 - 12:08

Does Watch and Wait Increase Distant Metastasis Risk in Rectal Cancer?

Article Type
Changed
Wed, 01/15/2025 - 02:47

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

  • Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
  • The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
  • A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
  • The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

  • Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
  • Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
  • Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
  • Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

  • Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
  • The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
  • A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
  • The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

  • Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
  • Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
  • Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
  • Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

  • Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
  • The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
  • A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
  • The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

  • Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
  • Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
  • Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
  • Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Wed, 01/08/2025 - 13:52
Un-Gate On Date
Wed, 01/08/2025 - 13:52
Use ProPublica
CFC Schedule Remove Status
Wed, 01/08/2025 - 13:52
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Wed, 01/08/2025 - 13:52

AI-Aided Colonoscopy’s ‘Intelligent’ Module Ups Polyp Detection

Article Type
Changed
Thu, 03/06/2025 - 11:09

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Dr. Nabil M. Mansour

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Publications
Topics
Sections

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Dr. Nabil M. Mansour

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Dr. Nabil M. Mansour

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Article Source

FROM THE LANCET GASTROENTEROLOGY & HEPATOLOGY

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Mon, 01/06/2025 - 09:34
Un-Gate On Date
Mon, 01/06/2025 - 09:34
Use ProPublica
CFC Schedule Remove Status
Mon, 01/06/2025 - 09:34
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Mon, 01/06/2025 - 09:34

Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban

Article Type
Changed
Fri, 01/10/2025 - 12:30
Display Headline

Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban

Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5

NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8

Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10

There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12

Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.

Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10

The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.

METHODS

This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.

Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.

Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.

Data Collection

Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.

The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.

Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.

Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.

Outcomes

Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.

All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.

The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.

Statistical Analysis

Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.

RESULTS

The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.

There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.

DISCUSSION

This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.

There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.

In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18

Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19

In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.

It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.

The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.

Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.

DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.

Limitations

The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.

This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.

CONCLUSIONS

This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.

References
  1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
  2. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
  3. Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
  4. Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
  5. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
  6. Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
  7. Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
  8. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
  9. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
  10. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
  11. Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
  12. Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
  13. Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
  14. Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
  15. Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
  16. . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
  17. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
  18. Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
  19. Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
  20. Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
Article PDF
Author and Disclosure Information

Rebecca Worsham, PharmDa; Robert Wood, PharmD, BCCCP, VHA-CMa,b; Andrea Jill Radford, PharmD, CACPa

Correspondence: Rebecca Worsham ([email protected])

Author affiliations: a James H. Quillen Veterans Affairs Medical Center, Mountain Home, Tennessee
bBill Gatton College of Pharmacy, East Tennessee State University, Johnson City

Author disclosures:The authors report no actual or potential conflicts of interest with regard to this article.

Fed Pract. 2024;41(12). Published online December 23. doi:10.12788/fp.0540

Issue
Federal Practitioner - 41(12)
Publications
Topics
Page Number
e1-e7
Sections
Author and Disclosure Information

Rebecca Worsham, PharmDa; Robert Wood, PharmD, BCCCP, VHA-CMa,b; Andrea Jill Radford, PharmD, CACPa

Correspondence: Rebecca Worsham ([email protected])

Author affiliations: a James H. Quillen Veterans Affairs Medical Center, Mountain Home, Tennessee
bBill Gatton College of Pharmacy, East Tennessee State University, Johnson City

Author disclosures:The authors report no actual or potential conflicts of interest with regard to this article.

Fed Pract. 2024;41(12). Published online December 23. doi:10.12788/fp.0540

Author and Disclosure Information

Rebecca Worsham, PharmDa; Robert Wood, PharmD, BCCCP, VHA-CMa,b; Andrea Jill Radford, PharmD, CACPa

Correspondence: Rebecca Worsham ([email protected])

Author affiliations: a James H. Quillen Veterans Affairs Medical Center, Mountain Home, Tennessee
bBill Gatton College of Pharmacy, East Tennessee State University, Johnson City

Author disclosures:The authors report no actual or potential conflicts of interest with regard to this article.

Fed Pract. 2024;41(12). Published online December 23. doi:10.12788/fp.0540

Article PDF
Article PDF

Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5

NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8

Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10

There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12

Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.

Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10

The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.

METHODS

This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.

Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.

Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.

Data Collection

Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.

The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.

Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.

Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.

Outcomes

Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.

All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.

The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.

Statistical Analysis

Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.

RESULTS

The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.

There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.

DISCUSSION

This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.

There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.

In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18

Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19

In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.

It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.

The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.

Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.

DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.

Limitations

The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.

This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.

CONCLUSIONS

This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.

Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5

NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8

Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10

There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12

Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.

Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10

The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.

METHODS

This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.

Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.

Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.

Data Collection

Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.

The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.

Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.

Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.

Outcomes

Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.

All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.

The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.

Statistical Analysis

Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.

RESULTS

The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.

There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.

DISCUSSION

This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.

There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.

In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18

Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19

In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.

It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.

The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.

Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.

DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.

Limitations

The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.

This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.

CONCLUSIONS

This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.

References
  1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
  2. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
  3. Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
  4. Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
  5. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
  6. Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
  7. Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
  8. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
  9. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
  10. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
  11. Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
  12. Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
  13. Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
  14. Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
  15. Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
  16. . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
  17. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
  18. Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
  19. Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
  20. Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
References
  1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
  2. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
  3. Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
  4. Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
  5. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
  6. Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
  7. Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
  8. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
  9. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
  10. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
  11. Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
  12. Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
  13. Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
  14. Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
  15. Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
  16. . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
  17. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
  18. Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
  19. Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
  20. Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
Issue
Federal Practitioner - 41(12)
Issue
Federal Practitioner - 41(12)
Page Number
e1-e7
Page Number
e1-e7
Publications
Publications
Topics
Article Type
Display Headline

Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban

Display Headline

Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban

Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Fri, 12/20/2024 - 11:22
Un-Gate On Date
Fri, 12/20/2024 - 11:22
Use ProPublica
CFC Schedule Remove Status
Fri, 12/20/2024 - 11:22
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Fri, 12/20/2024 - 11:22

Skin Cancer Risk Elevated Among Blood, Marrow Transplant Survivors

Article Type
Changed
Tue, 12/24/2024 - 05:40

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

  • The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
  • Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
  • The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

  • The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
  • A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
  • Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
  • The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

  • The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
  • Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
  • The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

  • The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
  • A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
  • Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
  • The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

  • The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
  • Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
  • The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

  • The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
  • A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
  • Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
  • The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Thu, 12/19/2024 - 13:32
Un-Gate On Date
Thu, 12/19/2024 - 13:32
Use ProPublica
CFC Schedule Remove Status
Thu, 12/19/2024 - 13:32
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Thu, 12/19/2024 - 13:32

How Are Patients Managing Intermediate-Risk Prostate Cancer?

Article Type
Changed
Tue, 12/17/2024 - 06:04

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Topics
Sections

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Thu, 12/12/2024 - 11:18
Un-Gate On Date
Thu, 12/12/2024 - 11:18
Use ProPublica
CFC Schedule Remove Status
Thu, 12/12/2024 - 11:18
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
survey writer start date
Thu, 12/12/2024 - 11:18