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IMPERIAL: Eluvia stent tops Zilver PTX for PAD
SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.
At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).
“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.
There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.
At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.
“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.
As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.
About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.
The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).
The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.
At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).
“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.
There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.
At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.
“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.
As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.
About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.
The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).
The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.
At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).
“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.
There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.
At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.
“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.
As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.
About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.
The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).
The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.
REPORTING FROM TCT 2018
Key clinical point: A drug-eluting stent under development for peripheral artery disease outperformed the only one currently on the market in the United States.
Major finding: At 12 months, primary patency was 86.8% in the Eluvia group versus 81.5% among those randomized to Zilver PTX.
Study details: IMPERIAL was a head-to-head randomized trial with 465 subjects comparing two stents for femoropopliteal PAD.
Disclosures: The work was funded and conducted by Boston Scientific. Most of the investigators disclosed financial ties to company; one was an employee.
First combo trial of mTOR/BRAF inhibition shows potential
A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.
The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.
“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.
The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.
Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.
Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.
“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”
The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.
SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.
A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.
The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.
“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.
The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.
Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.
Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.
“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”
The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.
SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.
A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.
The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.
“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.
The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.
Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.
Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.
“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”
The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.
SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.
FROM JCO PRECISION ONCOLOGY
Key clinical point: A combination of the mTOR inhibitor everolimus and the BRAF inhibitor vemurafenib is safe and effective against some treatment-refractory, BRAF-mutated solid tumors.
Major finding: Twenty-two percent (22%) of patients had a partial response to therapy.
Study details: A phase I, dose-escalation trial involving 20 patients with advanced, BRAF-mutated cancer that had progressed on MEK and/or BRAF inhibitor therapy.
Disclosures: The authors reported affiliations with Bayer, Baxter, Novartis, Roche, Trovagene, and others.
Source: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.
Residents curb IV antibiotic overuse in children
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.
Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.
They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.
To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.
The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.
That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.
Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.
Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.
A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.
The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.
Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.
There was no external funding, and the investigators had no disclosures.
REPORTING FROM PHM 2018
Key clinical point:
Major finding: The percentage of antibiotics given orally to children who were taking other enteral medications rose from 44% to 80% over 8 months, saving an estimated $30,000 annually.
Study details: Quality improvement project
Disclosures: There was no external funding, and the investigators didn’t have any disclosures.
CHMP supports new indication for venetoclax
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).
AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The EC typically makes an approval decision within 67 days of the CHMP’s opinion.
The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
Venetoclax is already EC-approved as monotherapy for:
- Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
- Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).
According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reaction (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reaction (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).
AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The EC typically makes an approval decision within 67 days of the CHMP’s opinion.
The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
Venetoclax is already EC-approved as monotherapy for:
- Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
- Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).
According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reaction (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reaction (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).
AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
The EC typically makes an approval decision within 67 days of the CHMP’s opinion.
The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.
Venetoclax is already EC-approved as monotherapy for:
- Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
- Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.
The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.
According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).
According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).
Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:
- Neutropenia (57.7% and 38.8%)
- Infections and infestations (17.5% and 21.8%)
- Anemia (10.8% and 13.8%)
- Thrombocytopenia (5.7% and 10.1%)
- Febrile neutropenia (3.6% and 9.6%)
- Pneumonia (5.2% and 8.0%)
- Infusion-related reaction (1.5% and 5.3%)
- Tumor lysis syndrome (3.1% and 1.1%)
- Hypotension (0% and 2.7%)
- Hyperglycemia (2.1% and 0%)
- Hypogammaglobulinemia (2.1% and 0%).
Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:
- Pneumonia (8.2% and 8.0%)
- Febrile neutropenia (3.6% and 8.5%)
- Pyrexia (2.6% and 6.9%)
- Anemia (1.5% and 2.7%)
- Infusion-related reaction (0.5% and 3.2%)
- Sepsis (0.5% and 2.1%)
- Tumor lysis syndrome (2.1% and 0.5%)
- Hypotension (0% and 2.7%).
Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.
Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.
Obesity plays role in sleep-disordered breathing in pregnancy
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.
An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.
Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.
There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.
However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.
The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.
Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.
“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”
However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.
“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.
The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
FROM JOURNAL OF SLEEP RESEARCH
Key clinical point:
Major finding: The relationship between hypertension in pregnancy and sleep-disordered breathing is only significant for more severe sleep-disordered breathing.
Study details: Prospective case-control study in 80 pregnant women.
Disclosures: The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.
Source: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.
Rivaroxaban bonus: Early unmasking of occult GI cancers
MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.
“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.
These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.
“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).
This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.
This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.
As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.
A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.
The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.
Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.
In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.
“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.
Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.
“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.
Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.
He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).
“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.
COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.
MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.
“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.
These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.
“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).
This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.
This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.
As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.
A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.
The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.
Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.
In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.
“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.
Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.
“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.
Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.
He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).
“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.
COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.
MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.
“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.
These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.
“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).
This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.
This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.
As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.
A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.
The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.
Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.
In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.
“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.
Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.
“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.
Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.
He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).
“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.
COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point:
Major finding: Among patients on rivaroxaban, 1 in 12 GI bleeding events was associated with an occult GI cancer.
Study details: This was a secondary analysis looking at cancers in COMPASS, a randomized trial of more than 27,000 patients on rivaroxaban and/or aspirin for vascular prevention.
Disclosures: The presenter reported receiving research grants from Bayer, which sponsored the COMPASS trial.
DIVA results similar for drug-eluting, bare-metal stents
Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.
The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.
The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.
While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.
The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)
A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.
Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.
There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.
Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.
Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.
SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.
The predominant use of second-generation drug-eluting stents in the DIVA study may explain why the researchers found no difference in outcomes for bare metal and drug-eluting stents.
Most patients in previous trials were treated with first-generation drug-eluting stents, but second-generation drug-eluting stents perform better than their first-generation counterparts in native coronary artery disease. One might think that this finding should also apply to saphenous vein bypass graft lesions in which atherosclerosis is more aggressive and the progress of the disease much faster, yet this was not the case in DIVA, and the study authors did not provide an explanation for this finding.
One possible reason for the comparability of outcomes in the drug-eluting stents and bare metal stents groups may be that saphenous vein bypass graft lesions may be more favorably disposed to paclitaxel, commonly used in first-generation drug-eluting stents, than the drugs found in the second-generation stents. The DIVA findings may indicate that the second-generation drug-eluting stents performed worse, not that the bare metal stents performed better.
Studies of only first-generation paclitaxel-eluting stents showed a sustained benefit. Any notion that the pathophysiology of saphenous vein grafts might make them more amenable to a bare metal stent while a drug-eluting stent is better suited for native vessels is purely speculative. Further research comparing the effect of different stent types in saphenous vein bypass graft failure is warranted.
Raban V. Jeger, MD, and Sven Möbius-Winkler, MD, made these remarks in an invited commentary. Dr. Jeger is with the University Hospital Basel (Switzerland), and Dr. Möbius-Winkler is with University Hospital Jena (Germany). Dr. Jeger disclosed he is the principal investigator of the BASKET-SAVAGE trial, which received funding from Boston Scientific Germany. Dr. Möbius-Winkler had no financial relationships to disclose.
The predominant use of second-generation drug-eluting stents in the DIVA study may explain why the researchers found no difference in outcomes for bare metal and drug-eluting stents.
Most patients in previous trials were treated with first-generation drug-eluting stents, but second-generation drug-eluting stents perform better than their first-generation counterparts in native coronary artery disease. One might think that this finding should also apply to saphenous vein bypass graft lesions in which atherosclerosis is more aggressive and the progress of the disease much faster, yet this was not the case in DIVA, and the study authors did not provide an explanation for this finding.
One possible reason for the comparability of outcomes in the drug-eluting stents and bare metal stents groups may be that saphenous vein bypass graft lesions may be more favorably disposed to paclitaxel, commonly used in first-generation drug-eluting stents, than the drugs found in the second-generation stents. The DIVA findings may indicate that the second-generation drug-eluting stents performed worse, not that the bare metal stents performed better.
Studies of only first-generation paclitaxel-eluting stents showed a sustained benefit. Any notion that the pathophysiology of saphenous vein grafts might make them more amenable to a bare metal stent while a drug-eluting stent is better suited for native vessels is purely speculative. Further research comparing the effect of different stent types in saphenous vein bypass graft failure is warranted.
Raban V. Jeger, MD, and Sven Möbius-Winkler, MD, made these remarks in an invited commentary. Dr. Jeger is with the University Hospital Basel (Switzerland), and Dr. Möbius-Winkler is with University Hospital Jena (Germany). Dr. Jeger disclosed he is the principal investigator of the BASKET-SAVAGE trial, which received funding from Boston Scientific Germany. Dr. Möbius-Winkler had no financial relationships to disclose.
The predominant use of second-generation drug-eluting stents in the DIVA study may explain why the researchers found no difference in outcomes for bare metal and drug-eluting stents.
Most patients in previous trials were treated with first-generation drug-eluting stents, but second-generation drug-eluting stents perform better than their first-generation counterparts in native coronary artery disease. One might think that this finding should also apply to saphenous vein bypass graft lesions in which atherosclerosis is more aggressive and the progress of the disease much faster, yet this was not the case in DIVA, and the study authors did not provide an explanation for this finding.
One possible reason for the comparability of outcomes in the drug-eluting stents and bare metal stents groups may be that saphenous vein bypass graft lesions may be more favorably disposed to paclitaxel, commonly used in first-generation drug-eluting stents, than the drugs found in the second-generation stents. The DIVA findings may indicate that the second-generation drug-eluting stents performed worse, not that the bare metal stents performed better.
Studies of only first-generation paclitaxel-eluting stents showed a sustained benefit. Any notion that the pathophysiology of saphenous vein grafts might make them more amenable to a bare metal stent while a drug-eluting stent is better suited for native vessels is purely speculative. Further research comparing the effect of different stent types in saphenous vein bypass graft failure is warranted.
Raban V. Jeger, MD, and Sven Möbius-Winkler, MD, made these remarks in an invited commentary. Dr. Jeger is with the University Hospital Basel (Switzerland), and Dr. Möbius-Winkler is with University Hospital Jena (Germany). Dr. Jeger disclosed he is the principal investigator of the BASKET-SAVAGE trial, which received funding from Boston Scientific Germany. Dr. Möbius-Winkler had no financial relationships to disclose.
Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.
The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.
The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.
While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.
The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)
A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.
Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.
There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.
Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.
Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.
SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.
Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.
The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.
The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.
While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.
The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)
A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.
Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.
There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.
Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.
Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.
SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.
FROM THE LANCET
Key clinical point: Drug-eluting and bare-metal stents had similar outcomes for saphenous vein bypass lesions.
Major finding: Target vessel failure was 17% for drug-eluting stents and 19% for bare metal stents.
Study details: The DIVA trial randomly assigned 599 patients with post-CABG saphenous vein bypass graft failure to drug-eluting or bare metal stents between Jan. 1, 2012, and Dec. 31, 2015.
Disclosures: Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.
Source: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.
Partial nephrectomies on rise for early-stage RCC
SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.
About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.
The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.
Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.
Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).
“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.
“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.
The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”
SOURCE: AUA Annual Meeting, Abstract PD07-04.
SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.
About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.
The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.
Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.
Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).
“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.
“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.
The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”
SOURCE: AUA Annual Meeting, Abstract PD07-04.
SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.
About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.
The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.
Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.
Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).
“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.
“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.
The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”
SOURCE: AUA Annual Meeting, Abstract PD07-04.
REPORTING FROM THE AUA ANNUAL MEETING
Key clinical point: Many patients who could undergo partial nephrectomy are still receiving radical nephrectomies.
Major finding: In 2014, 53% of patients with pT1a or pT1b RCC underwent partial nephrectomy.
Study details: Retrospective analysis of 142,000 patients.
Disclosures: The study was funded internally. Dr. Cahn reports having no relevant financial disclosures.
Source: Cahn D et al. AUA Annual Meeting, Abstract PD07-04.
Ulipristal reduces bleeding with contraceptive implant
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point:
Major finding: Treatment with ulipristal was associated with 5 fewer bleeding days per month, compared with placebo (P = .002).
Study details: The double-blind, placebo-controlled trial involved 65 women with etonogestrel implants who reported more than one bleeding episode in a 24-day time frame.
Disclosures: The study was funded by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences (NCATS). The authors reported financial disclosures related to Bayer and Merck.
Source: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
Severe influenza increases risk of invasive pulmonary aspergillosis in the ICU
Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.
Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.
The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.
Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.
Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.
At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.
AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.
The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).
The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”
Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”
The authors reported that they had no conflicts of interest.
SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1
Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.
Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.
The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.
Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.
Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.
At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.
AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.
The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).
The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”
Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”
The authors reported that they had no conflicts of interest.
SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1
Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.
Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.
The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.
Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.
Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.
At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.
AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.
The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).
The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”
Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”
The authors reported that they had no conflicts of interest.
SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: ICU admission for severe influenza as significant a risk factor should be included in the existing diagnostic criteria for predicting incidence of invasive pulmonary aspergillosis.
Major finding: Influenza is an independent risk factor associated with invasive pulmonary aspergillosis, with 90-day mortality rising from 28% to 51% when this fungal infection occurs.
Study details: Multicenter retrospective study of 432 adult patients with confirmed severe influenza admitted to the ICU with acute respiratory failure.
Disclosures: The authors reported that they had no conflicts of interest.
Source: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1.