Federal Practitioner

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

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

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

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

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

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

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

PHILADELPHIA – Aspirin may not be necessary or beneficial in patients with advanced heart failure who get a left ventricular assist device (LVAD), particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.

“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
 

Unexpected findings

“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”

Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.

“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
 

Shift of focus to therapy

The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.

“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”

But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”

Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.

“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”

Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.

This transcript has been edited for clarity.

It’s important for doctors to ask about erections. Not only do our patients and their partners care about them, but they are a marker for overall health. I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.

The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.

It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?

Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.

Courtesy Rachel S. Rubin, MD

Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

It’s important for doctors to ask about erections. Not only do our patients and their partners care about them, but they are a marker for overall health. I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.

The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.

It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?

Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.

Courtesy Rachel S. Rubin, MD

Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

It’s important for doctors to ask about erections. Not only do our patients and their partners care about them, but they are a marker for overall health. I mean it. Penis problems are very common and are an early sign that patients could have a cardiac event. Think about it: Clogging the arteries of the heart is called a heart attack; clogging the arteries to the penis is a penis attack, or as doctors like to call it, erectile dysfunction.

The arteries to the penis are only 1 mm in diameter. They develop plaque and clog the circulation long before the 3-mm cardiac arteries. So, it’s very important for primary care doctors to talk to their patients about erection health. And I’ll be honest: It’s easier to talk to patients about how lifestyle is affecting their penis health than it is to discuss how lifestyle affects longevity or prevents cancer. I get a lot of men to quit smoking because I tell them what it’s doing to their penises.

It can be challenging for doctors and patients to talk about penises. It doesn’t come naturally for many of us. If a 20-year-old comes in to my office with his 85-year-old grandfather and they both say their penises aren’t working, how do you figure out what’s going on? Do they even have the same thing wrong with them?

Here’s a fun and helpful tool that I use in my office. It’s called the Erection Hardness Score. It was developed around the time that Viagra came out, in 1998. It’s been game-changing for me to get patients more comfortable talking about their erection issues.

Courtesy Rachel S. Rubin, MD

Dr. Rubin is assistant clinical professor, department of urology, Georgetown University, Washington. She disclosed financial relationships with Absorption Pharmaceuticals, GlaxoSmithKline, and Endo Pharmaceuticals; has served as a speaker for Sprout; and has received research grant from Maternal Medical.

A version of this article appeared on Medscape.com.

The Canadian Cardiovascular Society has developed a four-stage classification of acute atherothrombotic myocardial infarction based on the severity of the injury to the myocardium.

Relying on more than 50 years of data on acute MI with reperfusion therapy, the society has identified the following four stages of progressively worsening myocardial tissue injury:

• Aborted MI (no or minimal myocardial necrosis).
• MI with significant cardiomyocyte necrosis but without microvascular injury.
• Cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (that is, “no reflow”).
• Cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage.

The classification is described in an expert consensus statement that was published in the Canadian Journal of Cardiology.

The new classification will allow for better risk stratification and more appropriate treatment and provide refined endpoints for clinical trials and translational research, according to the authors.

Currently, all patients with acute MI receive the same treatment, even though they may have different levels of tissue injury severity, statement author Andreas Kumar, MD, chair of the writing group and associate professor of medicine at Northern Ontario School of Medicine University, Sudbury, said in an interview.

“In some cases, treatment for a mild stage 1 acute MI may be deadly for someone with stage 4 hemorrhagic MI,” said Dr. Kumar.
 

Technological advances

The classification is based on decades of data. “The initial data were obtained with pathology studies in the 1970s. When cardiac MRI came around, around the year 2000, suddenly there was a noninvasive imaging method where we could investigate patients in vivo,” said Dr. Kumar. “We learned a lot about tissue changes in acute MI. And especially in the last 2 to 5 years, we have learned a lot about hemorrhagic MI. So, this then gave us enough knowledge to come up with this new classification.”

The idea of classifying acute MI came to Dr. Kumar and senior author Rohan Dharmakumar, PhD, executive director of the Krannert Cardiovascular Research Center at Indiana University, Indianapolis, when both were at the University of Toronto.

“This work has been years in the making,” Dr. Dharmakumar said in an interview. “We’ve been thinking about this for a long time, but we needed to get substantial layers of evidence to support the classification. We had a feeling about these stages for a long time, but that feeling needed to be substantiated.”

In 2022, Dr. Dharmakumar and Dr. Kumar observed that damage to the heart from MI was not only a result of ischemia caused by a blocked artery, but also a result of bleeding in the myocardium after the artery had been opened. Their findings were published in the Journal of the American College of Cardiology.

The author of an accompanying editorial lauded the investigators “for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.”

“Hemorrhagic MI is a very dangerous injury because hemorrhage itself causes a lot of problems,” said Dr. Kumar. “We reported that there is infarct expansion after reperfusion, so once you open up the vessel, the heart attack actually gets larger. We also showed that the remodeling of these hearts is worse. These patients take a second hit with hemorrhage occurring in the myocardium.”
 

Classification and staging

“The standard guideline therapy for somebody who comes into the hospital is to put in a stent, open the artery, have the patient stay in the hospital for 48-72 hours, and then be released home,” said Dr. Dharmukumar. “But here’s the problem. These two patients who are going back home have different levels of injury, yet they are taking the same medications. Even inside the hospital, we have heterogeneity in mortality risk. But we are not paying attention to one patient differently than the other, even though we should, because their injuries are very different.”

The CCS classification may provide endpoints and outcome measures beyond the commonly used clinical markers, which could lead to improved treatments to help patients recover from their cardiac events.

“We have this issue of rampant heart failure in acute MI survivors. We’ve gotten really good at saving patients from immediate death, but now we are just postponing some of the serious problems survivors are going to face, said Dr. Dharmukumar. “What are we doing for these patients who are really at risk? We’ve been treating every single patient the same way and we have not been paying attention to the very different stages of injury.”

In an accompanying editorial, Prakriti Gaba, MD, a clinical fellow in medicine at Brigham and Women’s Hospital, Boston, and Deepak L. Bhatt, MD, MPH, director of the Mount Sinai Fuster Heart Hospital, New York, wrote: “There is no doubt that the classification system proposed by the investigators is important and timely, as acute MI continues to account for substantial morbidity and mortality worldwide.”

Imaging and staging could be useful in guiding appropriate therapy, Bhatt said in an interview. “The authors’ hope, which I think is a very laudable one, is that more finely characterizing exactly what the extent of damage is and what the mechanism of damage is in a heart attack will make it possible to develop therapies that are particularly targeted to each of the stages,” he said.

“It is quite common to have the ability to do cardiac MRI at experienced cardiovascular centers, although this may not be true for smaller community hospitals,” Dr. Bhatt added. “But at least at larger hospitals, this will allow for much finer evaluation and assessment of exactly what is going on in that particular patient and how extensive the heart muscle damage is. Eventually, this will facilitate the development of therapies that are specifically targeted to treat each stage.”

Dr. Kumar is partly supported by a research grant from the Northern Ontario Academic Medicine Association. Dr. Dharmakumar was funded in part by grants from the U.S. National Institutes of Health. Dr. Dharmakumar has an ownership interest in Cardio-Theranostics. Dr. Bhatt has served on advisory boards for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys. He is a member of the board of directors of or holds stock in Angiowave, Boston VA Research Institute, Bristol-Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft. He has worked as a consultant for Broadview Ventures, and Hims. He has received honoraria from the American College of Cardiology, Arnold and Porter law firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, WebMD, and Wiley.

A version of this article appeared on Medscape.com.

The Canadian Cardiovascular Society has developed a four-stage classification of acute atherothrombotic myocardial infarction based on the severity of the injury to the myocardium.

Relying on more than 50 years of data on acute MI with reperfusion therapy, the society has identified the following four stages of progressively worsening myocardial tissue injury:

• Aborted MI (no or minimal myocardial necrosis).
• MI with significant cardiomyocyte necrosis but without microvascular injury.
• Cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (that is, “no reflow”).
• Cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage.

The classification is described in an expert consensus statement that was published in the Canadian Journal of Cardiology.

The new classification will allow for better risk stratification and more appropriate treatment and provide refined endpoints for clinical trials and translational research, according to the authors.

Currently, all patients with acute MI receive the same treatment, even though they may have different levels of tissue injury severity, statement author Andreas Kumar, MD, chair of the writing group and associate professor of medicine at Northern Ontario School of Medicine University, Sudbury, said in an interview.

“In some cases, treatment for a mild stage 1 acute MI may be deadly for someone with stage 4 hemorrhagic MI,” said Dr. Kumar.
 

Technological advances

The classification is based on decades of data. “The initial data were obtained with pathology studies in the 1970s. When cardiac MRI came around, around the year 2000, suddenly there was a noninvasive imaging method where we could investigate patients in vivo,” said Dr. Kumar. “We learned a lot about tissue changes in acute MI. And especially in the last 2 to 5 years, we have learned a lot about hemorrhagic MI. So, this then gave us enough knowledge to come up with this new classification.”

The idea of classifying acute MI came to Dr. Kumar and senior author Rohan Dharmakumar, PhD, executive director of the Krannert Cardiovascular Research Center at Indiana University, Indianapolis, when both were at the University of Toronto.

“This work has been years in the making,” Dr. Dharmakumar said in an interview. “We’ve been thinking about this for a long time, but we needed to get substantial layers of evidence to support the classification. We had a feeling about these stages for a long time, but that feeling needed to be substantiated.”

In 2022, Dr. Dharmakumar and Dr. Kumar observed that damage to the heart from MI was not only a result of ischemia caused by a blocked artery, but also a result of bleeding in the myocardium after the artery had been opened. Their findings were published in the Journal of the American College of Cardiology.

The author of an accompanying editorial lauded the investigators “for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.”

“Hemorrhagic MI is a very dangerous injury because hemorrhage itself causes a lot of problems,” said Dr. Kumar. “We reported that there is infarct expansion after reperfusion, so once you open up the vessel, the heart attack actually gets larger. We also showed that the remodeling of these hearts is worse. These patients take a second hit with hemorrhage occurring in the myocardium.”
 

Classification and staging

“The standard guideline therapy for somebody who comes into the hospital is to put in a stent, open the artery, have the patient stay in the hospital for 48-72 hours, and then be released home,” said Dr. Dharmukumar. “But here’s the problem. These two patients who are going back home have different levels of injury, yet they are taking the same medications. Even inside the hospital, we have heterogeneity in mortality risk. But we are not paying attention to one patient differently than the other, even though we should, because their injuries are very different.”

The CCS classification may provide endpoints and outcome measures beyond the commonly used clinical markers, which could lead to improved treatments to help patients recover from their cardiac events.

“We have this issue of rampant heart failure in acute MI survivors. We’ve gotten really good at saving patients from immediate death, but now we are just postponing some of the serious problems survivors are going to face, said Dr. Dharmukumar. “What are we doing for these patients who are really at risk? We’ve been treating every single patient the same way and we have not been paying attention to the very different stages of injury.”

In an accompanying editorial, Prakriti Gaba, MD, a clinical fellow in medicine at Brigham and Women’s Hospital, Boston, and Deepak L. Bhatt, MD, MPH, director of the Mount Sinai Fuster Heart Hospital, New York, wrote: “There is no doubt that the classification system proposed by the investigators is important and timely, as acute MI continues to account for substantial morbidity and mortality worldwide.”

Imaging and staging could be useful in guiding appropriate therapy, Bhatt said in an interview. “The authors’ hope, which I think is a very laudable one, is that more finely characterizing exactly what the extent of damage is and what the mechanism of damage is in a heart attack will make it possible to develop therapies that are particularly targeted to each of the stages,” he said.

“It is quite common to have the ability to do cardiac MRI at experienced cardiovascular centers, although this may not be true for smaller community hospitals,” Dr. Bhatt added. “But at least at larger hospitals, this will allow for much finer evaluation and assessment of exactly what is going on in that particular patient and how extensive the heart muscle damage is. Eventually, this will facilitate the development of therapies that are specifically targeted to treat each stage.”

Dr. Kumar is partly supported by a research grant from the Northern Ontario Academic Medicine Association. Dr. Dharmakumar was funded in part by grants from the U.S. National Institutes of Health. Dr. Dharmakumar has an ownership interest in Cardio-Theranostics. Dr. Bhatt has served on advisory boards for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys. He is a member of the board of directors of or holds stock in Angiowave, Boston VA Research Institute, Bristol-Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft. He has worked as a consultant for Broadview Ventures, and Hims. He has received honoraria from the American College of Cardiology, Arnold and Porter law firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, WebMD, and Wiley.

A version of this article appeared on Medscape.com.

The Canadian Cardiovascular Society has developed a four-stage classification of acute atherothrombotic myocardial infarction based on the severity of the injury to the myocardium.

Relying on more than 50 years of data on acute MI with reperfusion therapy, the society has identified the following four stages of progressively worsening myocardial tissue injury:

• Aborted MI (no or minimal myocardial necrosis).
• MI with significant cardiomyocyte necrosis but without microvascular injury.
• Cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (that is, “no reflow”).
• Cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage.

The classification is described in an expert consensus statement that was published in the Canadian Journal of Cardiology.

The new classification will allow for better risk stratification and more appropriate treatment and provide refined endpoints for clinical trials and translational research, according to the authors.

Currently, all patients with acute MI receive the same treatment, even though they may have different levels of tissue injury severity, statement author Andreas Kumar, MD, chair of the writing group and associate professor of medicine at Northern Ontario School of Medicine University, Sudbury, said in an interview.

“In some cases, treatment for a mild stage 1 acute MI may be deadly for someone with stage 4 hemorrhagic MI,” said Dr. Kumar.
 

Technological advances

The classification is based on decades of data. “The initial data were obtained with pathology studies in the 1970s. When cardiac MRI came around, around the year 2000, suddenly there was a noninvasive imaging method where we could investigate patients in vivo,” said Dr. Kumar. “We learned a lot about tissue changes in acute MI. And especially in the last 2 to 5 years, we have learned a lot about hemorrhagic MI. So, this then gave us enough knowledge to come up with this new classification.”

The idea of classifying acute MI came to Dr. Kumar and senior author Rohan Dharmakumar, PhD, executive director of the Krannert Cardiovascular Research Center at Indiana University, Indianapolis, when both were at the University of Toronto.

“This work has been years in the making,” Dr. Dharmakumar said in an interview. “We’ve been thinking about this for a long time, but we needed to get substantial layers of evidence to support the classification. We had a feeling about these stages for a long time, but that feeling needed to be substantiated.”

In 2022, Dr. Dharmakumar and Dr. Kumar observed that damage to the heart from MI was not only a result of ischemia caused by a blocked artery, but also a result of bleeding in the myocardium after the artery had been opened. Their findings were published in the Journal of the American College of Cardiology.

The author of an accompanying editorial lauded the investigators “for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.”

“Hemorrhagic MI is a very dangerous injury because hemorrhage itself causes a lot of problems,” said Dr. Kumar. “We reported that there is infarct expansion after reperfusion, so once you open up the vessel, the heart attack actually gets larger. We also showed that the remodeling of these hearts is worse. These patients take a second hit with hemorrhage occurring in the myocardium.”
 

Classification and staging

“The standard guideline therapy for somebody who comes into the hospital is to put in a stent, open the artery, have the patient stay in the hospital for 48-72 hours, and then be released home,” said Dr. Dharmukumar. “But here’s the problem. These two patients who are going back home have different levels of injury, yet they are taking the same medications. Even inside the hospital, we have heterogeneity in mortality risk. But we are not paying attention to one patient differently than the other, even though we should, because their injuries are very different.”

The CCS classification may provide endpoints and outcome measures beyond the commonly used clinical markers, which could lead to improved treatments to help patients recover from their cardiac events.

“We have this issue of rampant heart failure in acute MI survivors. We’ve gotten really good at saving patients from immediate death, but now we are just postponing some of the serious problems survivors are going to face, said Dr. Dharmukumar. “What are we doing for these patients who are really at risk? We’ve been treating every single patient the same way and we have not been paying attention to the very different stages of injury.”

In an accompanying editorial, Prakriti Gaba, MD, a clinical fellow in medicine at Brigham and Women’s Hospital, Boston, and Deepak L. Bhatt, MD, MPH, director of the Mount Sinai Fuster Heart Hospital, New York, wrote: “There is no doubt that the classification system proposed by the investigators is important and timely, as acute MI continues to account for substantial morbidity and mortality worldwide.”

Imaging and staging could be useful in guiding appropriate therapy, Bhatt said in an interview. “The authors’ hope, which I think is a very laudable one, is that more finely characterizing exactly what the extent of damage is and what the mechanism of damage is in a heart attack will make it possible to develop therapies that are particularly targeted to each of the stages,” he said.

“It is quite common to have the ability to do cardiac MRI at experienced cardiovascular centers, although this may not be true for smaller community hospitals,” Dr. Bhatt added. “But at least at larger hospitals, this will allow for much finer evaluation and assessment of exactly what is going on in that particular patient and how extensive the heart muscle damage is. Eventually, this will facilitate the development of therapies that are specifically targeted to treat each stage.”

Dr. Kumar is partly supported by a research grant from the Northern Ontario Academic Medicine Association. Dr. Dharmakumar was funded in part by grants from the U.S. National Institutes of Health. Dr. Dharmakumar has an ownership interest in Cardio-Theranostics. Dr. Bhatt has served on advisory boards for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys. He is a member of the board of directors of or holds stock in Angiowave, Boston VA Research Institute, Bristol-Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft. He has worked as a consultant for Broadview Ventures, and Hims. He has received honoraria from the American College of Cardiology, Arnold and Porter law firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, WebMD, and Wiley.

A version of this article appeared on Medscape.com.

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.