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In recurrent ovarian cancer, secondary surgery does not extend survival
Phase 3 findings ‘call into question’ merits of surgical cytoreduction
Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.
Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.
These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.
Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.
Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.
wrote Dr. Coleman and colleagues.
The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.
Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.
The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).
The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.
However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.
Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.
Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.
However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.
Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.
SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.
Phase 3 findings ‘call into question’ merits of surgical cytoreduction
Phase 3 findings ‘call into question’ merits of surgical cytoreduction
Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.
Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.
These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.
Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.
Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.
wrote Dr. Coleman and colleagues.
The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.
Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.
The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).
The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.
However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.
Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.
Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.
However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.
Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.
SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.
Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.
Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.
These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.
Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.
Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.
wrote Dr. Coleman and colleagues.
The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.
Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.
The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).
The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.
However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.
Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.
Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.
However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.
Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.
SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Children may develop prolonged headache after concussion
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
CHARLOTTE, N.C. – , according to research presented at the annual meeting of the Child Neurology Society. The headache may be migraine, chronic daily headache, tension-type headache, or a combination of these headaches.
“We strongly recommend that individuals who develop persistent headache after a concussion be evaluated and treated by a neurologist with experience in administering treatment for headache,” said Marcus Barissi, Weller Scholar at the Cleveland Clinic, and colleagues. “Using this approach, we hope that their prolonged headaches will be lessened.”
Few studies have examined prolonged pediatric postconcussion headache
The Centers for Disease Control and Prevention estimates that between 1.6 million and 3.8 million concussions occur annually during athletic and recreational activities in the United States. About 90% of concussions affect children or adolescents. The symptom most often reported after concussion is headache.
Few studies have focused on new persistent postconcussion headache (NPPCH) in children. Mr. Barissi and colleagues did not find any previous study that had examined prolonged headache following concussion in patients without prior chronic headache. They sought to ascertain the prognosis of patients with NPPCH and no history of prior headache, to describe this clinical entity, and to identify beneficial treatment methods.
The investigators retrospectively reviewed charts for approximately 2,000 patients who presented to the Cleveland Clinic pediatric neurology department between June 2017 and August 2018 for headaches. They identified 259 patients who received a diagnosis of concussion, 69 (27%) of whom had headaches for longer than 2 months after injury.
Mr. Barissi and colleagues emailed these patients, and 33 (48%) of them agreed to complete a questionnaire and participate in a 10-minute phone interview. Thirty-one patients (43%) could not be contacted, and eight (11%) declined to participate. All participants confirmed that they had not had consistent headache before the concussion and that chronic headache had arisen after concussion. To determine participants’ medical outcomes, the researchers compared participants’ initial assessment data with posttreatment data collected during the interview process.
Healthy behaviors increased after concussion
Of the 69 eligible participants, 38 (55%) were female. The population’s median age was 17. Twenty-eight (85%) of the 33 patients who completed the questionnaire considered the information and treatment that they had received to be beneficial. Twenty-five (78%) patients continued to have headache after several months, despite treatment.
Participants had withstood a mean of 1.72 concussions, and the mean age at first injury was 12.49 years. The most common cause of injury was a fall for males (36%) and an automobile accident for females (18%).
Forty-eight patients (70%) reported having two types of headache. Fifty-two patients (75%) had migraines, and 65 (94%) had chronic daily headache or tension-type headache. Forty-eight (70%) participants had a family history of headache.
In all, 64 patients (93%) had used a headache medication. The most common headache medications used were amitriptyline, topiramate, and cyproheptadine. Few patients were still taking these medications at several months after evaluation. The most common nonprescription medications used were Migravent (i.e., magnesium, riboflavin, coenzyme Q10, and butterbur), ondansetron, and melatonin. Furthermore, 61 patients (88%) participated in nonmedicinal therapy such as physical therapy, chiropractic therapy, and acupuncture.
After evaluation, patients engaged in several healthy behaviors (e.g., adequate exercise, proper use of over-the-counter medications, and drinking sufficient water) more frequently, but did not get adequate sleep. Sixty-five participants (94%) had undergone CT or MRI imaging, but the results did not improve understanding of headache etiology or treatment. Many patients missed several days of school, but average attendance improved after months of treatment.
Long-term outcomes
Thirty-one survey respondents (94%) reported that their emotional, cognitive, sleep, and somatic postconcussion symptoms had resolved. Nevertheless, a majority of participants still had headache. “The persistence of postconcussion symptoms is uncommon, but lasting headache is not,” said the researchers. “If patients are not properly educated, conditions may deteriorate, extending the duration of disability.” A longer study with a larger sample size could provide valuable information, said the researchers. Future work should examine objectively the efficacy of various medications used to treat NPPCH and determine the best methods of treatment for this syndrome, which “can cause prolonged pain, suffering, and lack of function,” they concluded.
The investigators did not report any study funding or disclosures.
SOURCE: Barissi M et al. CNS 2019, Abstract 95.
REPORTING FROM CNS 2019
FDA announces approval of fifth adalimumab biosimilar, Abrilada
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.
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.”
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.
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.”
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.
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.”
GALILEO, GALILEO 4D: Mixed results in post-TAVR anticoagulation
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.”
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.”
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.”
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.
REPORTING FROM AHA 2019
Free HIV self-tests for at-risk groups can increase awareness, testing frequency
A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.
“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.
To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.
Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).
When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.
they added, “and are another way to accelerate the end of the epidemic.”
The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.
SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.
A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.
“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.
To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.
Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).
When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.
they added, “and are another way to accelerate the end of the epidemic.”
The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.
SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.
A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.
“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.
To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.
Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).
When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.
they added, “and are another way to accelerate the end of the epidemic.”
The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.
SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Providing free HIV self-tests can lead to increased testing and more newly identified infections.
Major finding: About 77% of participants in the self-testing group tested three times or more in 12 months, compared with 22% of controls.
Study details: A 12-month longitudinal, two-group, randomized clinical trial of 2,665 men who have sex with men.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network.
Source: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.
ISCHEMIA trial hailed as practice changing
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
PHILADELPHIA – The eagerly awaited results of the ISCHEMIA trial – the largest-ever randomized trial of an initial invasive versus conservative management strategy for patients with stable ischemic heart disease – were emphatically declared practice-changing by interventional cardiologists and noninterventionalists alike at the American Heart Association scientific sessions.
At a median 3.3 years of follow-up of 5,179 participants with baseline moderate or severe ischemia at 320 sites in 37 countries in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy accompanied by optimal medical therapy (OMT) didn’t reduce the risk of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, compared with a conservative strategy of OMT alone. The rates at 4 years were 15.5% with the conservative strategy and 13.3% with the invasive strategy, reported study chair Judith S. Hochman, MD, professor of medicine and senior associate dean for clinical sciences at New York University.
Nor was there a significant between-group difference in the major secondary endpoint of cardiovascular death or MI: 13.9% with the conservative strategy, 11.7% with invasive management.
“The probability of at least a 10% benefit of the invasive strategy on all-cause mortality was less than 10%, based on a prespecified Bayesian analysis,” she added.
Prior to enrollment and randomization, CT angiography was routinely performed to rule out left main coronary artery disease.
Fifty-four percent of participants in the National Heart, Lung, and Blood Institute–funded trial had severe ischemia on a baseline noninvasive stress test. To the investigators’ surprise, patients with more severe ischemia or more extensive multivessel involvement didn’t do better with the invasive approach.
Almost a quarter (23%) of patients in the conservative management group crossed over to revascularization within 4 years.
Quality-of-life results
An invasive strategy did result in significantly greater improvement in angina control and quality of life, as measured using the Seattle Angina Questionnaire, than OMT alone in patients who had angina at least once a month at baseline.
“We have 100% confidence that there is a treatment benefit associated with an invasive approach early as well as late after randomization,” said John A. Spertus, MD, coprincipal investigator for the ISCHEMIA quality of life analysis.
Indeed, he calculated that, for patients with weekly angina, the number needed to treat with revascularization instead of OMT alone for one to be angina-free at 3 months was three.
However, in the 35% of ISCHEMIA participants who reported no angina within the past month at baseline, the invasive strategy offered no quality of life advantage, he added.
“I really think we need to hit ‘pause’ on asymptomatic revascularization. I just don’t see any benefit in patients without symptoms, left main disease excluded,” commented Dr. Spertus, director of health outcomes research at St. Luke’s Mid-America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
The reaction
ISCHEMIA addressed a key clinical issue that’s long been surrounded by equipoise because of a paucity of high-quality data. As such, it was deemed worthy of its own AHA Late-Breaking Science session. The assembled discussants agreed the results will change their clinical practice.
“Based on the trial results to date in the patient population studied in the trial, I as a clinician would feel comfortable advising my patients not to undergo the invasive strategy if their angina was absent or controlled or tolerated. I don’t think we should feel obligated to take them to the cath lab,” said Alice K. Jacobs, MD, an AHA past-president and professor of medicine and director of the cardiac catheterization laboratory and interventional cardiology at Boston Medical Center.
The ISCHEMIA trial has been the target of criticism because of its cost, prolonged duration, and shifting endpoints, but Glenn L. Levine, MD, praised the ISCHEMIA investigators for achieving “as well-designed and -executed a trial as one could practically do in the real world.” ISCHEMIA will undoubtedly be incorporated into AHA/American College of Cardiology guidelines on chest pain and on revascularization that are now in the process of being updated, predicted the cardiologist, who has chaired writing panels for numerous AHA/ACC guidelines.
“As someone who has been intimately involved with our national guidelines for the last 6 years, I say thank you to all the investigators and participants,” added Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. Debakey Medical Center, Houston.
“I’ll just say that this definitely will change my practice,” commented Brahmajee K. Nallamothu, MD, an interventional cardiologist and professor of medicine at the University of Michigan, Ann Arbor. “Just like the COURAGE trial taught me that not every blockage needs to have a stent in it right away, I think this is teaching me that not every patient with moderate-to-severe ischemia needs to go right away to the cath lab.”
Session cochair James de Lemos, MD, declared, “My take home is this is a remarkable finding. It’s medical proof that revascularization does not appear to have a marked effect.”
“I think the downstream implications of ISCHEMIA with regard to noninvasive testing are massive. I think that’s where will see more of an impact in our practice,” according to Dr. de Lemos, professor of medicine at the University of Texas Southwestern Medical Center and chief of the cardiology service at Parklawn Hospital in Dallas.
Numerous panelists expressed hope that the National Institutes of Health will fund a long-term extension of ISCHEMIA to learn if the results hold up.
The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire.
SOURCE: Hochman JS. AHA late breaker.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: .
Major finding: Immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
Study details: This international randomized trial included 5,129 patients with at least moderate ischemia who were assigned to initial invasive or conservative management and followed for a median of 3.3 years.
Disclosures: The ISCHEMIA trial was funded by the National Heart, Lung, and Blood Institute.
Source: Hochman JS. AHA 2019 late breaker.
DAPA-HF: Dapagliflozin’s HFrEF efficacy confirmed in nondiabetics
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
A labeling change for dapagliflozin that says the drug is approved for use in patients with heart failure with reduced ejection fraction (HFrEF) and without diabetes is critical so that payers will get on board with this new and important treatment. The evidence for efficacy and safety in patients without diabetes was so strong in the DAPA-HF trial that I don’t think a second trial will be needed for the Food and Drug Administration to add this indication to dapagliflozin’s label.
For patients with type 2 diabetes as well as HFrEF, it’s already full steam ahead to use dapagliflozin or another drug from the class of sodium glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin. However, so far these drugs are not being widely prescribed by clinicians to patients with HFrEF but without diabetes. We need to build up the familiarity of clinicians with the SGLT2 inhibitor drugs so that primary care physicians will feel comfortable starting HFrEF patients on them. It’s relatively easy to start patients on the drugs in this class because of their good safety and no signal of problems when using them with other HFrEF medications.
The growing list of key drugs to use on patients with HFrEF means that we need to become smarter on how we start patients on these agents. Currently it’s done without evidence for which order of introduction works best. We also need to confirm that all five types of drugs that now appear indicated for HFrEF patients are all truly additive: an angiotensin receptor blocker coupled with the angiotensin receptor neprilysin inhibitor sacubitril, a beta-blocker, a mineralocorticoid receptor antagonist, and now an SGLT2 inhibitor. I propose that researchers run studies that systematically stop one of these drugs to see whether the overall benefit to HFrEF patients remains unchanged, thereby identifying an agent that could be dropped from what is a growing list of drug classes, with possibly more classes to follow depending on results from studies now underway.
Christopher M. O’Connor, MD, is a heart failure physician and president of the Inova Heart and Vascular Institute in Falls Church, Va. He has been a consultant to Arena, Bayer, Bristol-Meyers Squibb, Merck, and Windtree Therapeutics. He made these comments in an interview.
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.
“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.
While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.
In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.
“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.
If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.
“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.
The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.
The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.
DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.
REPORTING FROM AHA 2019
Key clinical point: Dapaglifozin produced as much benefit in HFrEF patients without diabetes as it did in those with type 2 diabetes.
Major finding: The relative risk reduction with dapagliflozin was 26% in patients with a hemoglobin A1c of 5.6% or less.
Study details: DAPA-HF is a multicenter, randomized trial involving 4,744 patients with heart failure with reduced ejection fraction.
Disclosures: DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.
Source: McMurray JJV et al. AHA 19, Late-Breaking Science 1.
Suicide screening crucial in pediatric medical settings
and screening can take as little as 20 seconds, according to Lisa Horowitz, PhD, MPH, a staff scientist and clinical psychologist at the National Institute of Mental Health, Bethesda, Md.
But clinicians need to use validated screening instruments that are both population specific and site specific, and they need practice guidelines to treat patients screening positive.
Currently, many practitioners use depression screens – such as question #9 on suicide ideation and self harm on the Patient Health Questionnaire for Adolescents (PHQ-A) – to identify suicide risk, but preliminary data suggest these screens often are inadequate, Dr. Horowitz said. Just one question, especially one without precise language, does not appear to identify as many at-risk youths as more direct questions about suicidal thoughts and behaviors.
A Pathways to Clinical Care suicide risk screening work group therefore designed a three-tiered clinical pathway for suicide risk screenings in emergency departments, inpatient care, and outpatient primary care. It begins with the Ask Suicide-Screening Questions (ASQ), which takes about 20 seconds and was specifically developed for pediatric patients in the emergency department and validated in both inpatient and outpatient settings.
Dr Horowitz, also the lead principal investigator for development of the ASQ, currently is leading six National Institute of Mental Health studies to validate and implement the screening tool in medical settings. She explained the three-tiered system during a session on youth suicide screening at the Pediatric Academic Societies annual meeting in Baltimore this year.
If a patient screens positive on the ASQ, a trained clinician should conduct a brief suicide safety assessment (BSSA), which takes approximately 10 minutes, Dr Horowitz said. Those who screen positive on the BSSA should receive the Patient Resource List and then be referred for a full mental health and safety evaluation, which takes about 30 minutes. Resources, such as nurse scripts and parent/guardian flyers, are available at the NIMH website, as well as translations of the ASQ in Arabic, Chinese, Dutch, French, Hebrew, Italian, Japanese, Korean, Portuguese, Russian, Somali, Spanish, and Vietnamese.
Acknowledging the importance of suicide screening
During the same session, John V. Campo, MD, an assistant dean for behavioral health and professor of behavioral medicine and psychiatry at West Virginia University in Morgantown, discussed why suicide risk screening is so crucial in general medical settings. As someone who trained as a pediatrician before crossing over to behavioral health, he acknowledged that primary care physicians already have many priorities to cover in short visits, and that the national answer to most public health problems is to deal with it in primary care.
“Anyone who has done primary care pediatrics understands the challenges involved with screening for anything – particularly when you identify someone who is extensively at risk,” he said.
But suicide has a disproportionately high impact on young populations, and “identifying youth at risk for suicide identifies a group of young people who are at risk for a variety of threats to their health and well-being,” he said.
For youth aged 10-19 years in 2016, suicide was the second leading cause of death behind accidents, according to the Centers for Disease Control and Prevention (Natl Vital Stat Rep. 2018 Jun;67[4]:1-16). In fact, accidents, suicide, and homicide account for three-quarters of deaths among youth aged 10-24 years (Natl Vital Stat Rep. 2019 Jun;68[6]:1-77), yet it’s typically the other 25% that most physicians trained for in residency.
“Suicide kills more kids than cancer, heart disease, infections – all kinds, sepsis, meningitis, pneumonia, influenza, HIV, respiratory conditions. Suicide kills more young people every year than all of that [combined],” Dr. Campo said. “And yet, when you walk through a modern emergency department, we see all these specialized programs for those who present with physical trauma or chest pain or all these other things, but zero specialized mental health services. There’s a disconnect.”
There is some good news in the data, he said. Observational data have shown that suicide rates negatively correlate with indicators of better access to health and medical health services, and researchers increasingly are identifying proven strategies that help prevent suicide in young people – once they have been identified.
But that’s the problem, “and we all know it,” Dr. Campo continued. “Most youth who are at risk for suicide aren’t recognized, and those who are recognized most often are untreated or inadequately treated,” he said. Further, “the best predictor of future behavior is past behavior,” but most adolescents die by suicide on their first attempt.
Again, however, Dr. Campo pivoted to the good news. Data also have shown that most youth who die by suicide had at least one health contact in the previous year, which means there are opportunities for screening and intervention.
The most common risk factor for suicide is having a mental health or substance use condition, present in about 90% of completed suicides and affecting approximately one in five youth. Prevalence is even higher in those with physical health conditions and among those with Medicaid or no insurance (J Child Psychol Psychiatry. 2006 Mar-Apr;47[3-4]372-94).
Yet, “the majority of them have not been treated at all for mental disorder, which seems to be the most important remediable risk factor for suicide, and even fewer are in current treatment at the time of the death,” Dr. Campo said. Suicide also is correlated with a number of other high-risk behaviors or circumstances, such as “vulnerabilities to substance abuse, riding in a car with someone who is intoxicated, carrying a weapon to school, fighting, and meeting criteria for depression” (Pediatrics. 2010 May;125[5]:945-52). Screening for suicide risk therefore allows physicians to identify youth vulnerable to a wide range of risks, conditions, or death.
Overcoming barriers to suicide screening in primary care
Given the high prevalence of suicide and its link to so many other risks for youth, screening in primary care can send the message that suicide screening “really is a part of health care,” Dr. Campo said. Incorporating screening into primary care also can help overcome distrust of behavioral health specialists in the general public and stigma associated with behavioral health disorders.
Primary care screening emphasizes the importance and credibility of mental health and challenges attitudinal barriers to care, he said.
At the same time, however, he acknowledged that providers themselves often are uneasy about addressing behavioral health. Therefore, “having the guideline and the expectation [of suicide risk screening] really drives home the point that this needs to be integrated into the rest of primary care,” he said. “It’s also consistent with the idea of the medical home.” With suicide the second leading cause of death among youth, “if there’s anything that we’re going to be thinking about screening for, one would think suicide would be high on the list.”
In fact, observational evidence has shown that educating and training primary care providers to recognize people with depression or a high risk for suicide can reduce suicide attempts and the suicide rate, Dr. Campo said (JAMA Psychiatry. 2017 Jun 1;74[6]:563-70). It also can help with the mismatch between where at-risk patients are and where behavioral health specialists are. About 90% of behavioral health specialists work only in specialty settings, and only 5% typically work in general medical settings, he said. Yet “most people who are in mental distress or in crisis don’t present in specialty behavioral health settings. They present in general medical settings.”
More data are needed to demonstrate more definitively whether and how much suicide risk screening changes outcomes, but we know a few things, Dr. Campo said, summing up his key points: “We know suicide’s a major source of mortality in youth that’s been relatively neglected in pediatric health care. Second, we know that suicide risk is associated with risk for other important causes of death, for mental disorders, and for alcohol and substance use.
“We know that most suicide decedents are unrecognized prior to the time of death, and those who are recognized often are not treated. We know that the majority of suicide deaths occur on the very first attempt. We also know that we increasingly have treatments, mental disorders that can be identified, and remediable risk factors, and [that at-risk youth] typically present at general medical settings. Beyond that, focusing on the general medical setting has both conceptual and practical advantages as a site for really helping us to detect patients at risk and then managing them.”
No funding was used for the presentations. Dr. Horowitz and Dr. Campo had no relevant financial disclosures.
and screening can take as little as 20 seconds, according to Lisa Horowitz, PhD, MPH, a staff scientist and clinical psychologist at the National Institute of Mental Health, Bethesda, Md.
But clinicians need to use validated screening instruments that are both population specific and site specific, and they need practice guidelines to treat patients screening positive.
Currently, many practitioners use depression screens – such as question #9 on suicide ideation and self harm on the Patient Health Questionnaire for Adolescents (PHQ-A) – to identify suicide risk, but preliminary data suggest these screens often are inadequate, Dr. Horowitz said. Just one question, especially one without precise language, does not appear to identify as many at-risk youths as more direct questions about suicidal thoughts and behaviors.
A Pathways to Clinical Care suicide risk screening work group therefore designed a three-tiered clinical pathway for suicide risk screenings in emergency departments, inpatient care, and outpatient primary care. It begins with the Ask Suicide-Screening Questions (ASQ), which takes about 20 seconds and was specifically developed for pediatric patients in the emergency department and validated in both inpatient and outpatient settings.
Dr Horowitz, also the lead principal investigator for development of the ASQ, currently is leading six National Institute of Mental Health studies to validate and implement the screening tool in medical settings. She explained the three-tiered system during a session on youth suicide screening at the Pediatric Academic Societies annual meeting in Baltimore this year.
If a patient screens positive on the ASQ, a trained clinician should conduct a brief suicide safety assessment (BSSA), which takes approximately 10 minutes, Dr Horowitz said. Those who screen positive on the BSSA should receive the Patient Resource List and then be referred for a full mental health and safety evaluation, which takes about 30 minutes. Resources, such as nurse scripts and parent/guardian flyers, are available at the NIMH website, as well as translations of the ASQ in Arabic, Chinese, Dutch, French, Hebrew, Italian, Japanese, Korean, Portuguese, Russian, Somali, Spanish, and Vietnamese.
Acknowledging the importance of suicide screening
During the same session, John V. Campo, MD, an assistant dean for behavioral health and professor of behavioral medicine and psychiatry at West Virginia University in Morgantown, discussed why suicide risk screening is so crucial in general medical settings. As someone who trained as a pediatrician before crossing over to behavioral health, he acknowledged that primary care physicians already have many priorities to cover in short visits, and that the national answer to most public health problems is to deal with it in primary care.
“Anyone who has done primary care pediatrics understands the challenges involved with screening for anything – particularly when you identify someone who is extensively at risk,” he said.
But suicide has a disproportionately high impact on young populations, and “identifying youth at risk for suicide identifies a group of young people who are at risk for a variety of threats to their health and well-being,” he said.
For youth aged 10-19 years in 2016, suicide was the second leading cause of death behind accidents, according to the Centers for Disease Control and Prevention (Natl Vital Stat Rep. 2018 Jun;67[4]:1-16). In fact, accidents, suicide, and homicide account for three-quarters of deaths among youth aged 10-24 years (Natl Vital Stat Rep. 2019 Jun;68[6]:1-77), yet it’s typically the other 25% that most physicians trained for in residency.
“Suicide kills more kids than cancer, heart disease, infections – all kinds, sepsis, meningitis, pneumonia, influenza, HIV, respiratory conditions. Suicide kills more young people every year than all of that [combined],” Dr. Campo said. “And yet, when you walk through a modern emergency department, we see all these specialized programs for those who present with physical trauma or chest pain or all these other things, but zero specialized mental health services. There’s a disconnect.”
There is some good news in the data, he said. Observational data have shown that suicide rates negatively correlate with indicators of better access to health and medical health services, and researchers increasingly are identifying proven strategies that help prevent suicide in young people – once they have been identified.
But that’s the problem, “and we all know it,” Dr. Campo continued. “Most youth who are at risk for suicide aren’t recognized, and those who are recognized most often are untreated or inadequately treated,” he said. Further, “the best predictor of future behavior is past behavior,” but most adolescents die by suicide on their first attempt.
Again, however, Dr. Campo pivoted to the good news. Data also have shown that most youth who die by suicide had at least one health contact in the previous year, which means there are opportunities for screening and intervention.
The most common risk factor for suicide is having a mental health or substance use condition, present in about 90% of completed suicides and affecting approximately one in five youth. Prevalence is even higher in those with physical health conditions and among those with Medicaid or no insurance (J Child Psychol Psychiatry. 2006 Mar-Apr;47[3-4]372-94).
Yet, “the majority of them have not been treated at all for mental disorder, which seems to be the most important remediable risk factor for suicide, and even fewer are in current treatment at the time of the death,” Dr. Campo said. Suicide also is correlated with a number of other high-risk behaviors or circumstances, such as “vulnerabilities to substance abuse, riding in a car with someone who is intoxicated, carrying a weapon to school, fighting, and meeting criteria for depression” (Pediatrics. 2010 May;125[5]:945-52). Screening for suicide risk therefore allows physicians to identify youth vulnerable to a wide range of risks, conditions, or death.
Overcoming barriers to suicide screening in primary care
Given the high prevalence of suicide and its link to so many other risks for youth, screening in primary care can send the message that suicide screening “really is a part of health care,” Dr. Campo said. Incorporating screening into primary care also can help overcome distrust of behavioral health specialists in the general public and stigma associated with behavioral health disorders.
Primary care screening emphasizes the importance and credibility of mental health and challenges attitudinal barriers to care, he said.
At the same time, however, he acknowledged that providers themselves often are uneasy about addressing behavioral health. Therefore, “having the guideline and the expectation [of suicide risk screening] really drives home the point that this needs to be integrated into the rest of primary care,” he said. “It’s also consistent with the idea of the medical home.” With suicide the second leading cause of death among youth, “if there’s anything that we’re going to be thinking about screening for, one would think suicide would be high on the list.”
In fact, observational evidence has shown that educating and training primary care providers to recognize people with depression or a high risk for suicide can reduce suicide attempts and the suicide rate, Dr. Campo said (JAMA Psychiatry. 2017 Jun 1;74[6]:563-70). It also can help with the mismatch between where at-risk patients are and where behavioral health specialists are. About 90% of behavioral health specialists work only in specialty settings, and only 5% typically work in general medical settings, he said. Yet “most people who are in mental distress or in crisis don’t present in specialty behavioral health settings. They present in general medical settings.”
More data are needed to demonstrate more definitively whether and how much suicide risk screening changes outcomes, but we know a few things, Dr. Campo said, summing up his key points: “We know suicide’s a major source of mortality in youth that’s been relatively neglected in pediatric health care. Second, we know that suicide risk is associated with risk for other important causes of death, for mental disorders, and for alcohol and substance use.
“We know that most suicide decedents are unrecognized prior to the time of death, and those who are recognized often are not treated. We know that the majority of suicide deaths occur on the very first attempt. We also know that we increasingly have treatments, mental disorders that can be identified, and remediable risk factors, and [that at-risk youth] typically present at general medical settings. Beyond that, focusing on the general medical setting has both conceptual and practical advantages as a site for really helping us to detect patients at risk and then managing them.”
No funding was used for the presentations. Dr. Horowitz and Dr. Campo had no relevant financial disclosures.
and screening can take as little as 20 seconds, according to Lisa Horowitz, PhD, MPH, a staff scientist and clinical psychologist at the National Institute of Mental Health, Bethesda, Md.
But clinicians need to use validated screening instruments that are both population specific and site specific, and they need practice guidelines to treat patients screening positive.
Currently, many practitioners use depression screens – such as question #9 on suicide ideation and self harm on the Patient Health Questionnaire for Adolescents (PHQ-A) – to identify suicide risk, but preliminary data suggest these screens often are inadequate, Dr. Horowitz said. Just one question, especially one without precise language, does not appear to identify as many at-risk youths as more direct questions about suicidal thoughts and behaviors.
A Pathways to Clinical Care suicide risk screening work group therefore designed a three-tiered clinical pathway for suicide risk screenings in emergency departments, inpatient care, and outpatient primary care. It begins with the Ask Suicide-Screening Questions (ASQ), which takes about 20 seconds and was specifically developed for pediatric patients in the emergency department and validated in both inpatient and outpatient settings.
Dr Horowitz, also the lead principal investigator for development of the ASQ, currently is leading six National Institute of Mental Health studies to validate and implement the screening tool in medical settings. She explained the three-tiered system during a session on youth suicide screening at the Pediatric Academic Societies annual meeting in Baltimore this year.
If a patient screens positive on the ASQ, a trained clinician should conduct a brief suicide safety assessment (BSSA), which takes approximately 10 minutes, Dr Horowitz said. Those who screen positive on the BSSA should receive the Patient Resource List and then be referred for a full mental health and safety evaluation, which takes about 30 minutes. Resources, such as nurse scripts and parent/guardian flyers, are available at the NIMH website, as well as translations of the ASQ in Arabic, Chinese, Dutch, French, Hebrew, Italian, Japanese, Korean, Portuguese, Russian, Somali, Spanish, and Vietnamese.
Acknowledging the importance of suicide screening
During the same session, John V. Campo, MD, an assistant dean for behavioral health and professor of behavioral medicine and psychiatry at West Virginia University in Morgantown, discussed why suicide risk screening is so crucial in general medical settings. As someone who trained as a pediatrician before crossing over to behavioral health, he acknowledged that primary care physicians already have many priorities to cover in short visits, and that the national answer to most public health problems is to deal with it in primary care.
“Anyone who has done primary care pediatrics understands the challenges involved with screening for anything – particularly when you identify someone who is extensively at risk,” he said.
But suicide has a disproportionately high impact on young populations, and “identifying youth at risk for suicide identifies a group of young people who are at risk for a variety of threats to their health and well-being,” he said.
For youth aged 10-19 years in 2016, suicide was the second leading cause of death behind accidents, according to the Centers for Disease Control and Prevention (Natl Vital Stat Rep. 2018 Jun;67[4]:1-16). In fact, accidents, suicide, and homicide account for three-quarters of deaths among youth aged 10-24 years (Natl Vital Stat Rep. 2019 Jun;68[6]:1-77), yet it’s typically the other 25% that most physicians trained for in residency.
“Suicide kills more kids than cancer, heart disease, infections – all kinds, sepsis, meningitis, pneumonia, influenza, HIV, respiratory conditions. Suicide kills more young people every year than all of that [combined],” Dr. Campo said. “And yet, when you walk through a modern emergency department, we see all these specialized programs for those who present with physical trauma or chest pain or all these other things, but zero specialized mental health services. There’s a disconnect.”
There is some good news in the data, he said. Observational data have shown that suicide rates negatively correlate with indicators of better access to health and medical health services, and researchers increasingly are identifying proven strategies that help prevent suicide in young people – once they have been identified.
But that’s the problem, “and we all know it,” Dr. Campo continued. “Most youth who are at risk for suicide aren’t recognized, and those who are recognized most often are untreated or inadequately treated,” he said. Further, “the best predictor of future behavior is past behavior,” but most adolescents die by suicide on their first attempt.
Again, however, Dr. Campo pivoted to the good news. Data also have shown that most youth who die by suicide had at least one health contact in the previous year, which means there are opportunities for screening and intervention.
The most common risk factor for suicide is having a mental health or substance use condition, present in about 90% of completed suicides and affecting approximately one in five youth. Prevalence is even higher in those with physical health conditions and among those with Medicaid or no insurance (J Child Psychol Psychiatry. 2006 Mar-Apr;47[3-4]372-94).
Yet, “the majority of them have not been treated at all for mental disorder, which seems to be the most important remediable risk factor for suicide, and even fewer are in current treatment at the time of the death,” Dr. Campo said. Suicide also is correlated with a number of other high-risk behaviors or circumstances, such as “vulnerabilities to substance abuse, riding in a car with someone who is intoxicated, carrying a weapon to school, fighting, and meeting criteria for depression” (Pediatrics. 2010 May;125[5]:945-52). Screening for suicide risk therefore allows physicians to identify youth vulnerable to a wide range of risks, conditions, or death.
Overcoming barriers to suicide screening in primary care
Given the high prevalence of suicide and its link to so many other risks for youth, screening in primary care can send the message that suicide screening “really is a part of health care,” Dr. Campo said. Incorporating screening into primary care also can help overcome distrust of behavioral health specialists in the general public and stigma associated with behavioral health disorders.
Primary care screening emphasizes the importance and credibility of mental health and challenges attitudinal barriers to care, he said.
At the same time, however, he acknowledged that providers themselves often are uneasy about addressing behavioral health. Therefore, “having the guideline and the expectation [of suicide risk screening] really drives home the point that this needs to be integrated into the rest of primary care,” he said. “It’s also consistent with the idea of the medical home.” With suicide the second leading cause of death among youth, “if there’s anything that we’re going to be thinking about screening for, one would think suicide would be high on the list.”
In fact, observational evidence has shown that educating and training primary care providers to recognize people with depression or a high risk for suicide can reduce suicide attempts and the suicide rate, Dr. Campo said (JAMA Psychiatry. 2017 Jun 1;74[6]:563-70). It also can help with the mismatch between where at-risk patients are and where behavioral health specialists are. About 90% of behavioral health specialists work only in specialty settings, and only 5% typically work in general medical settings, he said. Yet “most people who are in mental distress or in crisis don’t present in specialty behavioral health settings. They present in general medical settings.”
More data are needed to demonstrate more definitively whether and how much suicide risk screening changes outcomes, but we know a few things, Dr. Campo said, summing up his key points: “We know suicide’s a major source of mortality in youth that’s been relatively neglected in pediatric health care. Second, we know that suicide risk is associated with risk for other important causes of death, for mental disorders, and for alcohol and substance use.
“We know that most suicide decedents are unrecognized prior to the time of death, and those who are recognized often are not treated. We know that the majority of suicide deaths occur on the very first attempt. We also know that we increasingly have treatments, mental disorders that can be identified, and remediable risk factors, and [that at-risk youth] typically present at general medical settings. Beyond that, focusing on the general medical setting has both conceptual and practical advantages as a site for really helping us to detect patients at risk and then managing them.”
No funding was used for the presentations. Dr. Horowitz and Dr. Campo had no relevant financial disclosures.
FDA approves cefiderocol for multidrug-resistant, complicated urinary tract infections
The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.
The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.
observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).
The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.
Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.
“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.
Fetroja is a product of Shionogi.
The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.
The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.
observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).
The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.
Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.
“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.
Fetroja is a product of Shionogi.
The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.
The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.
observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).
The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.
Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.
“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.
Fetroja is a product of Shionogi.
FROM THE FDA