The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Biologics are revolutionizing the treatment of atopic dermatitis (AD), but a dermatologist urged colleagues to keep in mind the value of traditional topical and systemic treatments.

Joseph F. Fowler Jr., MD, of the University of Louisville, Ky., offered these tips about AD treatment in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar:

• Keep the epidermal skin barrier in mind.

The epidermal skin barrier is abnormal in patients with AD, Dr. Fowler said, because of several possible factors: altered levels of natural moisturizing factor (which can be caused by a genetic mutation), imbalances between ceramides and lipids, and reduced aquaporin levels.

Enhancing the skin barrier is crucial in treating AD, he said, and products with these ingredients may help: ceramides, glycerin/glycerol (glucoside), colloidal oatmeal, and components of natural moisturizing factor.

• Expensive products are probably better.

“These products are available over the counter and via prescription,” he said. “Do they make the skin barrier stronger? The answer is they probably they do. But most do tend to be expensive, especially Rx products.”

Not all patients, of course, can afford the most expensive options. “You and your patients have to decide whether it’s better to get something like plain old Vaseline or a very inexpensive cream at Walmart that may be more accessible,” he said. “I tell patients that if the cost is not a big issue, these other products are probably better, and they will make your skin heal better and feel better. But if cost is a problem, use what you can afford.”

• Don’t forget about hypochlorous acid.

While it’s chemically similar to bleach, this product “doesn’t bleach your clothes or smell bleachy,” Dr. Fowler said. “It does have antibiotic and antipruritic effects.”

• For predictability, try methotrexate.

Methotrexate, an old workhorse in dermatology, remains an option, especially for patients who need alternatives to biologics, Dr. Fowler said. “I’ve used it much more in the last 10 years for eczema than for psoriasis and anything else. We’re used to using it, and I find it predictably effective at a dosage that’s similar to that for psoriasis.”

• Mycophenolate mofetil (CellCept) may be helpful.

Dr. Fowler’s research has shown that mycophenolate mofetil is useful in about 50% of chronic AD cases. “The problem with the drug is that you couldn’t tell which ones would get better and which ones wouldn’t.” Still, it can be an alternative to methotrexate and cyclosporine, he said.

• Cyclosporine is a short-term treatment.

“It’s like steroids on steroids,” Dr. Fowler said. “I’ve had to use it sometimes even in the age of biologics, which may not work as fast as we’d like in someone who’s really miserable.” The drug is linked to liver and kidney risks, he cautioned, and “you don’t want to be on it very long.”

• Ultraviolet light therapy can help.

This strategy works well “if they come in and get to the office and do it,” Dr. Fowler said. “We should remember it as an option.”

A patient who’s over 80 years old with bad AD has been getting narrow-band UVB treatments for at least 5 years, he said. “I just look at him every 3-4 months. Every time he says, ‘Can I keep coming and get my light treatments?’ and I say sure. At 80-plus, I’m not too worried about cutaneous malignancy or any other side effects.”

Dr. Fowler reported relationships with the speaker’s bureau of SmartPractice and ties with Asana, Johnson & Johnson, Lilly, Novartis and Pfizer. SDEF and this news organization are owned by the same parent company.

Brian Bolwell, MD, chairman of Cleveland Clinic Taussig Cancer Institute in Ohio, has received the 2019 Alfred and Norma Lerner Humanitarian Award.

Dr. Bolwell received the award “in honor of his 32 years of compassionate service as a physician leader and educator, along with his contributions to clinical and translational cancer research throughout the world,” according to a statement from Cleveland Clinic. The award recognizes “Cleveland Clinic physicians whose selfless dedication, boundless compassion, and tireless work have made the most profound and singular contribution to the good of humankind.”

In other Cleveland Clinic news, Halle Moore, MD, has been named director of breast medical oncology and codirector for the comprehensive breast cancer program at the clinic. She will assume this role in January 2020.

Cleveland Clinic has also added four new staff physicians to the department of hematology and medical oncology.

Shilpa Gupta, MD, has joined the clinic’s genitourinary cancer program. Dr. Gupta previously worked in the division of hematology, oncology, and transplantation at the University of Minnesota in Minneapolis, where she led the interdisciplinary solid tumor phase 1 program .

Khaled Hassan, MD, has joined the thoracic cancer program at Cleveland Clinic. Dr. Hassan was previously an assistant professor in the department of internal medicine, division of hematology/oncology at the University of Michigan in Ann Arbor. Suneel Kamath, MD, has joined the gastrointestinal cancer program at the clinic. Dr. Kamath was previously the hematology and medical oncology chief fellow at Northwestern University in Evanston, Ill.

jensmith@mdedge.com

Brian Bolwell, MD, chairman of Cleveland Clinic Taussig Cancer Institute in Ohio, has received the 2019 Alfred and Norma Lerner Humanitarian Award.

Dr. Bolwell received the award “in honor of his 32 years of compassionate service as a physician leader and educator, along with his contributions to clinical and translational cancer research throughout the world,” according to a statement from Cleveland Clinic. The award recognizes “Cleveland Clinic physicians whose selfless dedication, boundless compassion, and tireless work have made the most profound and singular contribution to the good of humankind.”

In other Cleveland Clinic news, Halle Moore, MD, has been named director of breast medical oncology and codirector for the comprehensive breast cancer program at the clinic. She will assume this role in January 2020.

Cleveland Clinic has also added four new staff physicians to the department of hematology and medical oncology.

Shilpa Gupta, MD, has joined the clinic’s genitourinary cancer program. Dr. Gupta previously worked in the division of hematology, oncology, and transplantation at the University of Minnesota in Minneapolis, where she led the interdisciplinary solid tumor phase 1 program .

Khaled Hassan, MD, has joined the thoracic cancer program at Cleveland Clinic. Dr. Hassan was previously an assistant professor in the department of internal medicine, division of hematology/oncology at the University of Michigan in Ann Arbor. Suneel Kamath, MD, has joined the gastrointestinal cancer program at the clinic. Dr. Kamath was previously the hematology and medical oncology chief fellow at Northwestern University in Evanston, Ill.

jensmith@mdedge.com

Brian Bolwell, MD, chairman of Cleveland Clinic Taussig Cancer Institute in Ohio, has received the 2019 Alfred and Norma Lerner Humanitarian Award.

Dr. Bolwell received the award “in honor of his 32 years of compassionate service as a physician leader and educator, along with his contributions to clinical and translational cancer research throughout the world,” according to a statement from Cleveland Clinic. The award recognizes “Cleveland Clinic physicians whose selfless dedication, boundless compassion, and tireless work have made the most profound and singular contribution to the good of humankind.”

In other Cleveland Clinic news, Halle Moore, MD, has been named director of breast medical oncology and codirector for the comprehensive breast cancer program at the clinic. She will assume this role in January 2020.

Cleveland Clinic has also added four new staff physicians to the department of hematology and medical oncology.

Shilpa Gupta, MD, has joined the clinic’s genitourinary cancer program. Dr. Gupta previously worked in the division of hematology, oncology, and transplantation at the University of Minnesota in Minneapolis, where she led the interdisciplinary solid tumor phase 1 program .

Khaled Hassan, MD, has joined the thoracic cancer program at Cleveland Clinic. Dr. Hassan was previously an assistant professor in the department of internal medicine, division of hematology/oncology at the University of Michigan in Ann Arbor. Suneel Kamath, MD, has joined the gastrointestinal cancer program at the clinic. Dr. Kamath was previously the hematology and medical oncology chief fellow at Northwestern University in Evanston, Ill.

jensmith@mdedge.com

The Food and Drug Administration has cleared the Pentax Medical Video ED34-i10T2 model duodenoscope for marketing in the United States, the first approved duodenoscope with a sterile, disposable elevator component.

Previous communication from the FDA has recommended to both health care facilities and duodenoscope manufacturers to transition to duodenoscopes with disposable components. Disposable designs reduce or eliminate the need for reprocessing certain components, a major source of between-patient duodenoscope contamination, the FDA said.

FDA approval for the Pentax device is based on a review through the premarket clearance pathway, and the manufacturer submitted evidence that the device is substantially equivalent to previous devices. Potential risks of using the Pentax duodenoscope include burns, electric shock, perforation, infection, and bleeding.

“Duodenoscopes with a disposable elevator component represent another major step toward lowering the risk of infection among patients who undergo procedures with these devices,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “Improving the safety of duodenoscopes is a top priority for the FDA since such devices remain critical to life-saving care for many patients in the U.S.”

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has cleared the Pentax Medical Video ED34-i10T2 model duodenoscope for marketing in the United States, the first approved duodenoscope with a sterile, disposable elevator component.

Previous communication from the FDA has recommended to both health care facilities and duodenoscope manufacturers to transition to duodenoscopes with disposable components. Disposable designs reduce or eliminate the need for reprocessing certain components, a major source of between-patient duodenoscope contamination, the FDA said.

FDA approval for the Pentax device is based on a review through the premarket clearance pathway, and the manufacturer submitted evidence that the device is substantially equivalent to previous devices. Potential risks of using the Pentax duodenoscope include burns, electric shock, perforation, infection, and bleeding.

“Duodenoscopes with a disposable elevator component represent another major step toward lowering the risk of infection among patients who undergo procedures with these devices,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “Improving the safety of duodenoscopes is a top priority for the FDA since such devices remain critical to life-saving care for many patients in the U.S.”

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has cleared the Pentax Medical Video ED34-i10T2 model duodenoscope for marketing in the United States, the first approved duodenoscope with a sterile, disposable elevator component.

Previous communication from the FDA has recommended to both health care facilities and duodenoscope manufacturers to transition to duodenoscopes with disposable components. Disposable designs reduce or eliminate the need for reprocessing certain components, a major source of between-patient duodenoscope contamination, the FDA said.

FDA approval for the Pentax device is based on a review through the premarket clearance pathway, and the manufacturer submitted evidence that the device is substantially equivalent to previous devices. Potential risks of using the Pentax duodenoscope include burns, electric shock, perforation, infection, and bleeding.

“Duodenoscopes with a disposable elevator component represent another major step toward lowering the risk of infection among patients who undergo procedures with these devices,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “Improving the safety of duodenoscopes is a top priority for the FDA since such devices remain critical to life-saving care for many patients in the U.S.”

Find the full press release on the FDA website.

lfranki@mdedge.com

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

November is National Diabetes Month, which gives SVS members the perfect opportunity to further educate their patients and loved ones with the SVS Foundation Patient flier on diabetes and vascular disease. These are available in both English and Spanish and can be downloaded instantly. You may also send patients and referrers to our Diabetes and Vascular Disease page. This holds several resources that might be useful for education purposes. Spread awareness and education using the many resources the SVS has to offer.

November is National Diabetes Month, which gives SVS members the perfect opportunity to further educate their patients and loved ones with the SVS Foundation Patient flier on diabetes and vascular disease. These are available in both English and Spanish and can be downloaded instantly. You may also send patients and referrers to our Diabetes and Vascular Disease page. This holds several resources that might be useful for education purposes. Spread awareness and education using the many resources the SVS has to offer.

November is National Diabetes Month, which gives SVS members the perfect opportunity to further educate their patients and loved ones with the SVS Foundation Patient flier on diabetes and vascular disease. These are available in both English and Spanish and can be downloaded instantly. You may also send patients and referrers to our Diabetes and Vascular Disease page. This holds several resources that might be useful for education purposes. Spread awareness and education using the many resources the SVS has to offer.

SVSConnect gives members an opportunity to share tough cases, discuss new breakthroughs in the industry and/or seek trusty advice from other professionals. Currently a post about Peer Support through the new SVS Member Support Program is one of the many discussions that users are engaging in. This post kicks off a series of discussion posts by the SVS Wellness Task Force, in collaboration with SurgeonMasters, that will focus on improving surgeons’ well-being, practice performance and patient outcomes. It is recommended that all who access SVSConnect on their mobile device download the app. This is the most user-friendly way to access the community and is an easy download. Follow the steps on this PDF to download the app. Reach out to communications@vascularsociety.org with any questions.

SVSConnect gives members an opportunity to share tough cases, discuss new breakthroughs in the industry and/or seek trusty advice from other professionals. Currently a post about Peer Support through the new SVS Member Support Program is one of the many discussions that users are engaging in. This post kicks off a series of discussion posts by the SVS Wellness Task Force, in collaboration with SurgeonMasters, that will focus on improving surgeons’ well-being, practice performance and patient outcomes. It is recommended that all who access SVSConnect on their mobile device download the app. This is the most user-friendly way to access the community and is an easy download. Follow the steps on this PDF to download the app. Reach out to communications@vascularsociety.org with any questions.

SVSConnect gives members an opportunity to share tough cases, discuss new breakthroughs in the industry and/or seek trusty advice from other professionals. Currently a post about Peer Support through the new SVS Member Support Program is one of the many discussions that users are engaging in. This post kicks off a series of discussion posts by the SVS Wellness Task Force, in collaboration with SurgeonMasters, that will focus on improving surgeons’ well-being, practice performance and patient outcomes. It is recommended that all who access SVSConnect on their mobile device download the app. This is the most user-friendly way to access the community and is an easy download. Follow the steps on this PDF to download the app. Reach out to communications@vascularsociety.org with any questions.

PHILADELPHIA – The results of the first randomized prospective trial of an anticoagulation strategy versus standard dual antiplatelet (DAPT) therapy for patients undergoing transcatheter aortic valve replacement (TAVR) show that routine anticoagulation is not suitable for all comers in a high-risk population.

In the main GALILEO trial of elderly patients after TAVR, those who received an investigational anticoagulation strategy with the direct factor Xa inhibitor rivaroxaban (Xarelto; Bayer/Janssen) had worse survival and more thromboembolic and bleeding events than patients who received standard DAPT.

However, in the GALILEO 4D substudy of patients who underwent four-dimensional computed tomography (4DCT) randomized to the two therapies, those in the rivaroxaban arm were less likely to show subclinical leaflet motion abnormalities and leaflet thickening.

Preliminary results from GALILEO were disclosed in an October 3, 2018, “Dear Healthcare Professional” letter from Bayer, and the trial was stopped after a median of 17 months due to safety concerns.

The full data analysis from GALILEO as well as the results from GALILEO 4D were presented at the American Heart Association scientific sessions to coincide with their publication on Nov. 16, 2019, in the New England Journal of Medicine.

The takeaway message is that, despite the positive imaging finding in GALILEO 4D, “there is no reason to give 10 mg rivaroxaban-based treatment routinely after TAVR in patients who don’t need anticoagulation anyhow,” lead author in the main GALILEO trial, George D. Dangas, MD, PhD, Mount Sinai Hospital, New York, said in an interview.

However, because rivaroxaban had an effect in reducing the clots on leaflets, he said, further investigation is required to determine the optimal therapeutic strategy after TAVR.

Similarly, the assigned discussant for GALILEO, Elaine Hylek, MD, of Boston University said in an interview that “we just don’t know right now what the overall added benefit of an oral anticoagulant would be in this high-risk patient population after having a TAVR.”

Copyright American Heart Association

Ole De Backer, MD, PhD, of Rigshospitalet University Hospital, Copenhagen, lead author of the GALILEO 4D substudy, concluded that, although the rivaroxaban-based strategy was associated with fewer valve abnormalities in this analysis, those positive outcomes need to be taken in context with worse clinical outcomes in the main GALILEO trial.

GALILEO

Guidelines recommend DAPT after TAVR, but this advice is based on expert consensus or small studies, the GALILEO study authors noted. Several years ago, there were random case reports and then case series of patients who had undergone TAVR or surgical aortic valve replacement (SAVR) and developed clots around the valve, Dr. Dangas explained.

These developments coincided with the first available high-quality CT angiography images that captured valve abnormalities that had not been seen before.

In parallel, there were rare reports of stroke and transient ischemic attack (TIA) that may have been associated with TAVR or SAVR. This triggered a series of studies to investigate an anticoagulation strategy after TAVR.

From December 2015 to May 2018, GALILEO enrolled 1,644 patients at 136 sites in 16 countries who had undergone successful TAVR, and had no indication for an anticoagulant (e.g., no atrial fibrillation).

The patients had a mean age of 80.6 years (plus or minus 6.6 years) and 49.5% were female. The median time from TAVR to randomization was 2 days (range, 0-8 days).

Half were randomized to receive an antithrombotic strategy, rivaroxaban 10 mg once daily plus aspirin 75-100 mg once daily for the first 90 days followed by rivaroxaban alone. The other half received an antiplatelet-based strategy, aspirin 75-100 mg once daily plus clopidogrel 75 mg once daily for the first 90 days followed by aspirin alone.

In the intention-to-treat analysis, death or first thromboembolic event, the primary efficacy outcome, occurred in 105 patients in the rivaroxaban group and 78 patients in the antiplatelet group (hazard ratio, 1.35; 95% CI, 1.01-1.81; P = .04).

Major, disabling, or life-threatening bleeding, the primary safety outcome, occurred in 46 and 31 patients, respectively (HR, 1.50; P = .08).

A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (HR, 1.69; 95% CI, 1.13-2.53).

The individuals who were enrolled in this study were 80 and older, Dr. Hylek pointed out. “The age in and of itself is an uncontested risk factor for everything, whether it be bleeding, embolic event, or obviously mortality.”

Although the dose was half that used to prevent stroke in patients with atrial fibrillation, perhaps a “twice-daily lower dose” might be the way to go, moving forward, she said.

Patients who did not have atrial fibrillation may have developed atrial fibrillation in the interim, and “you would have to change the dose of the rivaroxaban.”

Also, patients who may have been taking aspirin for 5 or 10 years and “survived” aspirin, who were then newly exposed to an anticoagulant, would be more likely to experience bleeding.

“I certainly wouldn’t close the door on novel anticoagulants,” she concluded. “There are still other drug trials that are out there with this TAVR population. We’ll wait for that,” and see if the results corroborate these findings.

The high-risk patients may turn out to be a potential niche group for drugs being developed to inhibit factor XIa, she speculated.

GALILEO 4D

However, despite the negative results of the overall GALILEO study, results from the substudy that used 4DCT to evaluate function of the bioprosthetic aortic valves suggested rivaroxaban may have potentially beneficial effects on valve function.

The results showed that patients on the rivaroxaban and aspirin regimen had lower rates of subclinical reduced leaflet motion and leaflet thickening than patients on the antiplatelet strategy, said Dr. De Backer, reporting on behalf of the GALILEO-4D investigators.

The substudy evaluated 205 patients who had 4DCT 90 days after TAVR. The primary substudy endpoint was at least one prosthetic valve leaflet with a grade 3 or higher motion reduction, which 2 of 97 patients in the rivaroxaban group had (2.1%) versus 11 of 101 in the antiplatelet group (10.9%, P = .01).

“This indicated an 80% greater reduction of the primary endpoint in the rivaroxaban arm,” Dr. De Backer said. The chief secondary endpoint, the proportion of patients with at least one thickened leaflet, was met by 12.4% of the rivaroxaban group and 32.4% of the antiplatelet arm, “a 60% significant reduction by rivaroxaban,” Dr. De Backer said.

However, when the 10 patients in each group who didn’t adhere to the study drug regimen were excluded, he said, “then we see no single patient had reduced leaflet motion of grade 3 or more in the rivaroxaban arm.”

Another takeaway from the substudy is the ineffectiveness of transthoracic echocardiography as opposed to 4DCT in TAVR patients. Echocardiography (ECG) failed to show any significant differences in the mean valve gradient between the treatment groups, Dr. De Backer said.

Eleven patients who didn’t have leaflet thickening (7.3%) and 7 patients who did (15.9%) showed an increase of 5 mm Hg or more in the mean valve gradient on echo. ECG also showed a similar increase in the mean valve gradient in 14 patients who had no to moderate reduced leaflet motion (grade 3 or lower, 7.7%) and in four patients (30.8) who had grade 3 or higher reduced leaflet motion.

“This basically confirms results from observational studies that transthoracic echocardiography is often not good enough to detect these phenomena,” Dr. De Backer said.

The percentages of substudy patients who had major clinical events – major bleeding, thromboembolic events, or death at 90 days – were each less than 3%, he said. “There were too few clinical events to permit any assessment of the impact of leaflet thickening or reduced leaflet motion on clinical outcomes,” he said.

That lack of clarity with regard to clinical events is one of the questions the study leaves unanswered, said discussant Victoria Delgado, MD, PhD, of Leiden University Medical Center in the Netherlands.

“With stroke or TIA, there are too few events to draw any conclusions,” she said of the substudy. “We don’t know when we need to use CT, when we need to evaluate these patients, or maybe when we should go for more advanced imaging techniques where we can see the biology of those changes in the leaflets.” Hopefully, she said, future studies provide those insights.

“CT can be more sensitive than ECG to see these subclinical changes,” she said, “but the open questions that we have are to see if there is a correlation between thrombosis rate on imaging versus the stroke rate.”

The substudy’s conclusion on ECG, however, has been borne out by previous retrospective studies, Dr. Delgado added.

Robert A. Harrington, MD, of Stanford Medicine, tried to put the seemingly conflicting findings of the main GALILEO study and the 4D substudy into context.

“There you have the disconnect between the mechanism and the clinical observation and those are sometimes difficult to reconcile because the assumption is that the mechanism leads to the clinical outcome.”

While the main study shows that routine anticoagulation after TAVR is not indicated, the findings raise questions about the risk of clots forming on bioprosthetic valves. “Yes, maybe there are clots forming on these valves, but maybe that’s not causing the bad clinical outcomes,” Dr. Harrington said.

The findings also raise questions about the use of newer anticoagulants to prevent stroke post TAVR, he said. “It appears that warfarin is better than the newer anticoagulants for reasons that aren’t entirely clear.”

Dr. Dangas, lead author of the main GALILEO trial, said the substudy results could help design future trials of even-lower doses of anticoagulation in a more selective group of TAVR patients.

“In order to decrease the clots, first of all you don’t need the full dose of anticoagulation; even a low dose may do the trick,” he said. Further investigations can evaluate the clinical significance of having a blood clot in the valve as an indication for anticoagulation versus antiplatelet therapy.

“Even though this obviously doesn’t mean you’re going to have a stroke in a year or two,” Dr. Dangas said, “could it perhaps mean that the valve is not going to have such a good durability later on?”

Perhaps future studies of anticoagulation in TAVR should concentrate on patients who actually have clotting in the valve, he said.

The trial was supported by Bayer and Janssen. Dr. Dangas reported receiving grants from Bayer during the conduct of the study, personal fees from Bayer and Janssen, grants and personal fees from Daiichi-Sankyo, and “other” funding from Medtronic outside the submitted work. Dr. De Backer reported receiving grants from Bayer during the conduct of the study and personal fees from Abbott and Boston Scientific outside the submitted work.

SOURCE: Dangas GD and De Backer O. AHA 19, Late-Breaking Science 3 session.

This article also appears on Medscape.com.

PHILADELPHIA – The results of the first randomized prospective trial of an anticoagulation strategy versus standard dual antiplatelet (DAPT) therapy for patients undergoing transcatheter aortic valve replacement (TAVR) show that routine anticoagulation is not suitable for all comers in a high-risk population.

In the main GALILEO trial of elderly patients after TAVR, those who received an investigational anticoagulation strategy with the direct factor Xa inhibitor rivaroxaban (Xarelto; Bayer/Janssen) had worse survival and more thromboembolic and bleeding events than patients who received standard DAPT.

However, in the GALILEO 4D substudy of patients who underwent four-dimensional computed tomography (4DCT) randomized to the two therapies, those in the rivaroxaban arm were less likely to show subclinical leaflet motion abnormalities and leaflet thickening.

Preliminary results from GALILEO were disclosed in an October 3, 2018, “Dear Healthcare Professional” letter from Bayer, and the trial was stopped after a median of 17 months due to safety concerns.

The full data analysis from GALILEO as well as the results from GALILEO 4D were presented at the American Heart Association scientific sessions to coincide with their publication on Nov. 16, 2019, in the New England Journal of Medicine.

The takeaway message is that, despite the positive imaging finding in GALILEO 4D, “there is no reason to give 10 mg rivaroxaban-based treatment routinely after TAVR in patients who don’t need anticoagulation anyhow,” lead author in the main GALILEO trial, George D. Dangas, MD, PhD, Mount Sinai Hospital, New York, said in an interview.

However, because rivaroxaban had an effect in reducing the clots on leaflets, he said, further investigation is required to determine the optimal therapeutic strategy after TAVR.

Similarly, the assigned discussant for GALILEO, Elaine Hylek, MD, of Boston University said in an interview that “we just don’t know right now what the overall added benefit of an oral anticoagulant would be in this high-risk patient population after having a TAVR.”

Copyright American Heart Association

Ole De Backer, MD, PhD, of Rigshospitalet University Hospital, Copenhagen, lead author of the GALILEO 4D substudy, concluded that, although the rivaroxaban-based strategy was associated with fewer valve abnormalities in this analysis, those positive outcomes need to be taken in context with worse clinical outcomes in the main GALILEO trial.

GALILEO

Guidelines recommend DAPT after TAVR, but this advice is based on expert consensus or small studies, the GALILEO study authors noted. Several years ago, there were random case reports and then case series of patients who had undergone TAVR or surgical aortic valve replacement (SAVR) and developed clots around the valve, Dr. Dangas explained.

These developments coincided with the first available high-quality CT angiography images that captured valve abnormalities that had not been seen before.

In parallel, there were rare reports of stroke and transient ischemic attack (TIA) that may have been associated with TAVR or SAVR. This triggered a series of studies to investigate an anticoagulation strategy after TAVR.

From December 2015 to May 2018, GALILEO enrolled 1,644 patients at 136 sites in 16 countries who had undergone successful TAVR, and had no indication for an anticoagulant (e.g., no atrial fibrillation).

The patients had a mean age of 80.6 years (plus or minus 6.6 years) and 49.5% were female. The median time from TAVR to randomization was 2 days (range, 0-8 days).

Half were randomized to receive an antithrombotic strategy, rivaroxaban 10 mg once daily plus aspirin 75-100 mg once daily for the first 90 days followed by rivaroxaban alone. The other half received an antiplatelet-based strategy, aspirin 75-100 mg once daily plus clopidogrel 75 mg once daily for the first 90 days followed by aspirin alone.

In the intention-to-treat analysis, death or first thromboembolic event, the primary efficacy outcome, occurred in 105 patients in the rivaroxaban group and 78 patients in the antiplatelet group (hazard ratio, 1.35; 95% CI, 1.01-1.81; P = .04).

Major, disabling, or life-threatening bleeding, the primary safety outcome, occurred in 46 and 31 patients, respectively (HR, 1.50; P = .08).

A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (HR, 1.69; 95% CI, 1.13-2.53).

The individuals who were enrolled in this study were 80 and older, Dr. Hylek pointed out. “The age in and of itself is an uncontested risk factor for everything, whether it be bleeding, embolic event, or obviously mortality.”

Although the dose was half that used to prevent stroke in patients with atrial fibrillation, perhaps a “twice-daily lower dose” might be the way to go, moving forward, she said.

Patients who did not have atrial fibrillation may have developed atrial fibrillation in the interim, and “you would have to change the dose of the rivaroxaban.”

Also, patients who may have been taking aspirin for 5 or 10 years and “survived” aspirin, who were then newly exposed to an anticoagulant, would be more likely to experience bleeding.

“I certainly wouldn’t close the door on novel anticoagulants,” she concluded. “There are still other drug trials that are out there with this TAVR population. We’ll wait for that,” and see if the results corroborate these findings.

The high-risk patients may turn out to be a potential niche group for drugs being developed to inhibit factor XIa, she speculated.

GALILEO 4D

However, despite the negative results of the overall GALILEO study, results from the substudy that used 4DCT to evaluate function of the bioprosthetic aortic valves suggested rivaroxaban may have potentially beneficial effects on valve function.

The results showed that patients on the rivaroxaban and aspirin regimen had lower rates of subclinical reduced leaflet motion and leaflet thickening than patients on the antiplatelet strategy, said Dr. De Backer, reporting on behalf of the GALILEO-4D investigators.

The substudy evaluated 205 patients who had 4DCT 90 days after TAVR. The primary substudy endpoint was at least one prosthetic valve leaflet with a grade 3 or higher motion reduction, which 2 of 97 patients in the rivaroxaban group had (2.1%) versus 11 of 101 in the antiplatelet group (10.9%, P = .01).

“This indicated an 80% greater reduction of the primary endpoint in the rivaroxaban arm,” Dr. De Backer said. The chief secondary endpoint, the proportion of patients with at least one thickened leaflet, was met by 12.4% of the rivaroxaban group and 32.4% of the antiplatelet arm, “a 60% significant reduction by rivaroxaban,” Dr. De Backer said.

However, when the 10 patients in each group who didn’t adhere to the study drug regimen were excluded, he said, “then we see no single patient had reduced leaflet motion of grade 3 or more in the rivaroxaban arm.”

Another takeaway from the substudy is the ineffectiveness of transthoracic echocardiography as opposed to 4DCT in TAVR patients. Echocardiography (ECG) failed to show any significant differences in the mean valve gradient between the treatment groups, Dr. De Backer said.

Eleven patients who didn’t have leaflet thickening (7.3%) and 7 patients who did (15.9%) showed an increase of 5 mm Hg or more in the mean valve gradient on echo. ECG also showed a similar increase in the mean valve gradient in 14 patients who had no to moderate reduced leaflet motion (grade 3 or lower, 7.7%) and in four patients (30.8) who had grade 3 or higher reduced leaflet motion.

“This basically confirms results from observational studies that transthoracic echocardiography is often not good enough to detect these phenomena,” Dr. De Backer said.

The percentages of substudy patients who had major clinical events – major bleeding, thromboembolic events, or death at 90 days – were each less than 3%, he said. “There were too few clinical events to permit any assessment of the impact of leaflet thickening or reduced leaflet motion on clinical outcomes,” he said.

That lack of clarity with regard to clinical events is one of the questions the study leaves unanswered, said discussant Victoria Delgado, MD, PhD, of Leiden University Medical Center in the Netherlands.

“With stroke or TIA, there are too few events to draw any conclusions,” she said of the substudy. “We don’t know when we need to use CT, when we need to evaluate these patients, or maybe when we should go for more advanced imaging techniques where we can see the biology of those changes in the leaflets.” Hopefully, she said, future studies provide those insights.

“CT can be more sensitive than ECG to see these subclinical changes,” she said, “but the open questions that we have are to see if there is a correlation between thrombosis rate on imaging versus the stroke rate.”

The substudy’s conclusion on ECG, however, has been borne out by previous retrospective studies, Dr. Delgado added.

Robert A. Harrington, MD, of Stanford Medicine, tried to put the seemingly conflicting findings of the main GALILEO study and the 4D substudy into context.

“There you have the disconnect between the mechanism and the clinical observation and those are sometimes difficult to reconcile because the assumption is that the mechanism leads to the clinical outcome.”

While the main study shows that routine anticoagulation after TAVR is not indicated, the findings raise questions about the risk of clots forming on bioprosthetic valves. “Yes, maybe there are clots forming on these valves, but maybe that’s not causing the bad clinical outcomes,” Dr. Harrington said.

The findings also raise questions about the use of newer anticoagulants to prevent stroke post TAVR, he said. “It appears that warfarin is better than the newer anticoagulants for reasons that aren’t entirely clear.”

Dr. Dangas, lead author of the main GALILEO trial, said the substudy results could help design future trials of even-lower doses of anticoagulation in a more selective group of TAVR patients.

“In order to decrease the clots, first of all you don’t need the full dose of anticoagulation; even a low dose may do the trick,” he said. Further investigations can evaluate the clinical significance of having a blood clot in the valve as an indication for anticoagulation versus antiplatelet therapy.

“Even though this obviously doesn’t mean you’re going to have a stroke in a year or two,” Dr. Dangas said, “could it perhaps mean that the valve is not going to have such a good durability later on?”

Perhaps future studies of anticoagulation in TAVR should concentrate on patients who actually have clotting in the valve, he said.

The trial was supported by Bayer and Janssen. Dr. Dangas reported receiving grants from Bayer during the conduct of the study, personal fees from Bayer and Janssen, grants and personal fees from Daiichi-Sankyo, and “other” funding from Medtronic outside the submitted work. Dr. De Backer reported receiving grants from Bayer during the conduct of the study and personal fees from Abbott and Boston Scientific outside the submitted work.

SOURCE: Dangas GD and De Backer O. AHA 19, Late-Breaking Science 3 session.

This article also appears on Medscape.com.

PHILADELPHIA – The results of the first randomized prospective trial of an anticoagulation strategy versus standard dual antiplatelet (DAPT) therapy for patients undergoing transcatheter aortic valve replacement (TAVR) show that routine anticoagulation is not suitable for all comers in a high-risk population.

In the main GALILEO trial of elderly patients after TAVR, those who received an investigational anticoagulation strategy with the direct factor Xa inhibitor rivaroxaban (Xarelto; Bayer/Janssen) had worse survival and more thromboembolic and bleeding events than patients who received standard DAPT.

However, in the GALILEO 4D substudy of patients who underwent four-dimensional computed tomography (4DCT) randomized to the two therapies, those in the rivaroxaban arm were less likely to show subclinical leaflet motion abnormalities and leaflet thickening.

Preliminary results from GALILEO were disclosed in an October 3, 2018, “Dear Healthcare Professional” letter from Bayer, and the trial was stopped after a median of 17 months due to safety concerns.

The full data analysis from GALILEO as well as the results from GALILEO 4D were presented at the American Heart Association scientific sessions to coincide with their publication on Nov. 16, 2019, in the New England Journal of Medicine.

The takeaway message is that, despite the positive imaging finding in GALILEO 4D, “there is no reason to give 10 mg rivaroxaban-based treatment routinely after TAVR in patients who don’t need anticoagulation anyhow,” lead author in the main GALILEO trial, George D. Dangas, MD, PhD, Mount Sinai Hospital, New York, said in an interview.

However, because rivaroxaban had an effect in reducing the clots on leaflets, he said, further investigation is required to determine the optimal therapeutic strategy after TAVR.

Similarly, the assigned discussant for GALILEO, Elaine Hylek, MD, of Boston University said in an interview that “we just don’t know right now what the overall added benefit of an oral anticoagulant would be in this high-risk patient population after having a TAVR.”

Copyright American Heart Association

Ole De Backer, MD, PhD, of Rigshospitalet University Hospital, Copenhagen, lead author of the GALILEO 4D substudy, concluded that, although the rivaroxaban-based strategy was associated with fewer valve abnormalities in this analysis, those positive outcomes need to be taken in context with worse clinical outcomes in the main GALILEO trial.

GALILEO

Guidelines recommend DAPT after TAVR, but this advice is based on expert consensus or small studies, the GALILEO study authors noted. Several years ago, there were random case reports and then case series of patients who had undergone TAVR or surgical aortic valve replacement (SAVR) and developed clots around the valve, Dr. Dangas explained.

These developments coincided with the first available high-quality CT angiography images that captured valve abnormalities that had not been seen before.

In parallel, there were rare reports of stroke and transient ischemic attack (TIA) that may have been associated with TAVR or SAVR. This triggered a series of studies to investigate an anticoagulation strategy after TAVR.

From December 2015 to May 2018, GALILEO enrolled 1,644 patients at 136 sites in 16 countries who had undergone successful TAVR, and had no indication for an anticoagulant (e.g., no atrial fibrillation).

The patients had a mean age of 80.6 years (plus or minus 6.6 years) and 49.5% were female. The median time from TAVR to randomization was 2 days (range, 0-8 days).

Half were randomized to receive an antithrombotic strategy, rivaroxaban 10 mg once daily plus aspirin 75-100 mg once daily for the first 90 days followed by rivaroxaban alone. The other half received an antiplatelet-based strategy, aspirin 75-100 mg once daily plus clopidogrel 75 mg once daily for the first 90 days followed by aspirin alone.

In the intention-to-treat analysis, death or first thromboembolic event, the primary efficacy outcome, occurred in 105 patients in the rivaroxaban group and 78 patients in the antiplatelet group (hazard ratio, 1.35; 95% CI, 1.01-1.81; P = .04).

Major, disabling, or life-threatening bleeding, the primary safety outcome, occurred in 46 and 31 patients, respectively (HR, 1.50; P = .08).

A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (HR, 1.69; 95% CI, 1.13-2.53).

The individuals who were enrolled in this study were 80 and older, Dr. Hylek pointed out. “The age in and of itself is an uncontested risk factor for everything, whether it be bleeding, embolic event, or obviously mortality.”

Although the dose was half that used to prevent stroke in patients with atrial fibrillation, perhaps a “twice-daily lower dose” might be the way to go, moving forward, she said.

Patients who did not have atrial fibrillation may have developed atrial fibrillation in the interim, and “you would have to change the dose of the rivaroxaban.”

Also, patients who may have been taking aspirin for 5 or 10 years and “survived” aspirin, who were then newly exposed to an anticoagulant, would be more likely to experience bleeding.

“I certainly wouldn’t close the door on novel anticoagulants,” she concluded. “There are still other drug trials that are out there with this TAVR population. We’ll wait for that,” and see if the results corroborate these findings.

The high-risk patients may turn out to be a potential niche group for drugs being developed to inhibit factor XIa, she speculated.

GALILEO 4D

However, despite the negative results of the overall GALILEO study, results from the substudy that used 4DCT to evaluate function of the bioprosthetic aortic valves suggested rivaroxaban may have potentially beneficial effects on valve function.

The results showed that patients on the rivaroxaban and aspirin regimen had lower rates of subclinical reduced leaflet motion and leaflet thickening than patients on the antiplatelet strategy, said Dr. De Backer, reporting on behalf of the GALILEO-4D investigators.

The substudy evaluated 205 patients who had 4DCT 90 days after TAVR. The primary substudy endpoint was at least one prosthetic valve leaflet with a grade 3 or higher motion reduction, which 2 of 97 patients in the rivaroxaban group had (2.1%) versus 11 of 101 in the antiplatelet group (10.9%, P = .01).

“This indicated an 80% greater reduction of the primary endpoint in the rivaroxaban arm,” Dr. De Backer said. The chief secondary endpoint, the proportion of patients with at least one thickened leaflet, was met by 12.4% of the rivaroxaban group and 32.4% of the antiplatelet arm, “a 60% significant reduction by rivaroxaban,” Dr. De Backer said.

However, when the 10 patients in each group who didn’t adhere to the study drug regimen were excluded, he said, “then we see no single patient had reduced leaflet motion of grade 3 or more in the rivaroxaban arm.”

Another takeaway from the substudy is the ineffectiveness of transthoracic echocardiography as opposed to 4DCT in TAVR patients. Echocardiography (ECG) failed to show any significant differences in the mean valve gradient between the treatment groups, Dr. De Backer said.

Eleven patients who didn’t have leaflet thickening (7.3%) and 7 patients who did (15.9%) showed an increase of 5 mm Hg or more in the mean valve gradient on echo. ECG also showed a similar increase in the mean valve gradient in 14 patients who had no to moderate reduced leaflet motion (grade 3 or lower, 7.7%) and in four patients (30.8) who had grade 3 or higher reduced leaflet motion.

“This basically confirms results from observational studies that transthoracic echocardiography is often not good enough to detect these phenomena,” Dr. De Backer said.

The percentages of substudy patients who had major clinical events – major bleeding, thromboembolic events, or death at 90 days – were each less than 3%, he said. “There were too few clinical events to permit any assessment of the impact of leaflet thickening or reduced leaflet motion on clinical outcomes,” he said.

That lack of clarity with regard to clinical events is one of the questions the study leaves unanswered, said discussant Victoria Delgado, MD, PhD, of Leiden University Medical Center in the Netherlands.

“With stroke or TIA, there are too few events to draw any conclusions,” she said of the substudy. “We don’t know when we need to use CT, when we need to evaluate these patients, or maybe when we should go for more advanced imaging techniques where we can see the biology of those changes in the leaflets.” Hopefully, she said, future studies provide those insights.

“CT can be more sensitive than ECG to see these subclinical changes,” she said, “but the open questions that we have are to see if there is a correlation between thrombosis rate on imaging versus the stroke rate.”

The substudy’s conclusion on ECG, however, has been borne out by previous retrospective studies, Dr. Delgado added.

Robert A. Harrington, MD, of Stanford Medicine, tried to put the seemingly conflicting findings of the main GALILEO study and the 4D substudy into context.

“There you have the disconnect between the mechanism and the clinical observation and those are sometimes difficult to reconcile because the assumption is that the mechanism leads to the clinical outcome.”

While the main study shows that routine anticoagulation after TAVR is not indicated, the findings raise questions about the risk of clots forming on bioprosthetic valves. “Yes, maybe there are clots forming on these valves, but maybe that’s not causing the bad clinical outcomes,” Dr. Harrington said.

The findings also raise questions about the use of newer anticoagulants to prevent stroke post TAVR, he said. “It appears that warfarin is better than the newer anticoagulants for reasons that aren’t entirely clear.”

Dr. Dangas, lead author of the main GALILEO trial, said the substudy results could help design future trials of even-lower doses of anticoagulation in a more selective group of TAVR patients.

“In order to decrease the clots, first of all you don’t need the full dose of anticoagulation; even a low dose may do the trick,” he said. Further investigations can evaluate the clinical significance of having a blood clot in the valve as an indication for anticoagulation versus antiplatelet therapy.

“Even though this obviously doesn’t mean you’re going to have a stroke in a year or two,” Dr. Dangas said, “could it perhaps mean that the valve is not going to have such a good durability later on?”

Perhaps future studies of anticoagulation in TAVR should concentrate on patients who actually have clotting in the valve, he said.

The trial was supported by Bayer and Janssen. Dr. Dangas reported receiving grants from Bayer during the conduct of the study, personal fees from Bayer and Janssen, grants and personal fees from Daiichi-Sankyo, and “other” funding from Medtronic outside the submitted work. Dr. De Backer reported receiving grants from Bayer during the conduct of the study and personal fees from Abbott and Boston Scientific outside the submitted work.

SOURCE: Dangas GD and De Backer O. AHA 19, Late-Breaking Science 3 session.

This article also appears on Medscape.com.

Abstracts and videos for the 2020 Vascular Annual Meeting will be accepted now through January 15. The submission process may be completed on a smartphone or tablet computer. The Video Committee encourages submissions in areas such as dialysis access, lower extremity revascularization, surgical bypass procedures, venous interventions, management of adverse events and more. Read more and begin the submission process here.

Abstracts and videos for the 2020 Vascular Annual Meeting will be accepted now through January 15. The submission process may be completed on a smartphone or tablet computer. The Video Committee encourages submissions in areas such as dialysis access, lower extremity revascularization, surgical bypass procedures, venous interventions, management of adverse events and more. Read more and begin the submission process here.

Abstracts and videos for the 2020 Vascular Annual Meeting will be accepted now through January 15. The submission process may be completed on a smartphone or tablet computer. The Video Committee encourages submissions in areas such as dialysis access, lower extremity revascularization, surgical bypass procedures, venous interventions, management of adverse events and more. Read more and begin the submission process here.