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FDA approves Vabomere for complicated UTI in adults
The Food and Drug Administration has approved Vabomere (meropenem and vaborbactam) for adults with complicated urinary tract infection (cUTI), including pyelonephritis caused by susceptible Enterobacteriaceae, the agency has announced.
The approval was based on results of the TANGO 1 trial, a phase 3, multicenter, double-blind study of 545 adult patients with cUTI. Overall, 98.4% of patients treated with Vabomere saw improvement in symptoms and negative urine culture tests by the end of intravenous treatment, compared with 94.3% of those treated with piperacillin/tazobactam (95% confidence interval, 0.3%-8.8%). Improvement continued in about 77% of patients treated with Vabomere who had resolved symptoms 7 days after completing treatment, compared with about 73% of those who were treated with piperacillin/tazobactam, the FDA said Aug. 29 in a press release.
Headache, infusion site reactions, and diarrhea were common adverse effects of Vabomere. The drug also has been associated with allergic reactions and seizures, so it should not be administered to patients with a history of anaphylaxis.
“Vabomere represents a significant new advancement in addressing [Klebsiella pneumoniae carbapenemase]-producing Enterobacteriaceae, for which there are currently limited treatment options,” Clive A. Meanwell, MD, PhD, chief executive officer of The Medicines Company, said in the statement.
Rempex Pharmaceuticals, a Medicines Company unit, received the approval. The Medicines Company said the drug is expected to be available before the end of the year.
The Food and Drug Administration has approved Vabomere (meropenem and vaborbactam) for adults with complicated urinary tract infection (cUTI), including pyelonephritis caused by susceptible Enterobacteriaceae, the agency has announced.
The approval was based on results of the TANGO 1 trial, a phase 3, multicenter, double-blind study of 545 adult patients with cUTI. Overall, 98.4% of patients treated with Vabomere saw improvement in symptoms and negative urine culture tests by the end of intravenous treatment, compared with 94.3% of those treated with piperacillin/tazobactam (95% confidence interval, 0.3%-8.8%). Improvement continued in about 77% of patients treated with Vabomere who had resolved symptoms 7 days after completing treatment, compared with about 73% of those who were treated with piperacillin/tazobactam, the FDA said Aug. 29 in a press release.
Headache, infusion site reactions, and diarrhea were common adverse effects of Vabomere. The drug also has been associated with allergic reactions and seizures, so it should not be administered to patients with a history of anaphylaxis.
“Vabomere represents a significant new advancement in addressing [Klebsiella pneumoniae carbapenemase]-producing Enterobacteriaceae, for which there are currently limited treatment options,” Clive A. Meanwell, MD, PhD, chief executive officer of The Medicines Company, said in the statement.
Rempex Pharmaceuticals, a Medicines Company unit, received the approval. The Medicines Company said the drug is expected to be available before the end of the year.
The Food and Drug Administration has approved Vabomere (meropenem and vaborbactam) for adults with complicated urinary tract infection (cUTI), including pyelonephritis caused by susceptible Enterobacteriaceae, the agency has announced.
The approval was based on results of the TANGO 1 trial, a phase 3, multicenter, double-blind study of 545 adult patients with cUTI. Overall, 98.4% of patients treated with Vabomere saw improvement in symptoms and negative urine culture tests by the end of intravenous treatment, compared with 94.3% of those treated with piperacillin/tazobactam (95% confidence interval, 0.3%-8.8%). Improvement continued in about 77% of patients treated with Vabomere who had resolved symptoms 7 days after completing treatment, compared with about 73% of those who were treated with piperacillin/tazobactam, the FDA said Aug. 29 in a press release.
Headache, infusion site reactions, and diarrhea were common adverse effects of Vabomere. The drug also has been associated with allergic reactions and seizures, so it should not be administered to patients with a history of anaphylaxis.
“Vabomere represents a significant new advancement in addressing [Klebsiella pneumoniae carbapenemase]-producing Enterobacteriaceae, for which there are currently limited treatment options,” Clive A. Meanwell, MD, PhD, chief executive officer of The Medicines Company, said in the statement.
Rempex Pharmaceuticals, a Medicines Company unit, received the approval. The Medicines Company said the drug is expected to be available before the end of the year.
VIDEO: Clopidogrel bests ticagrelor in PCI for ACS in real-world study
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The 1-year composite endpoint of all-cause mortality, MI, stroke, or major bleeding occurred in 5.1% of ACS patients who underwent PCI using newer-generation drug-eluting stents followed by clopidogrel-based DAPT, compared with 7.8% who received ticagrelor-based DAPT.
Data source: This unique design for a prospective observational registry study compared 1-year outcomes in 2,062 consecutive ACS patients who underwent PCI at a single high-volume center, half before a regional switch from clopidogrel- to ticagrelor-based DAPT and half afterward.
Disclosures: CHANGE DAPT was an investigator-initiated study conducted without external funding. The presenter reported having no financial conflicts of interest.
HERDOO2 may guide duration of treatment for unprovoked VTE
Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?
Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.
Setting: Forty-four referral centers in seven countries.
Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.
Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.
Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.
Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?
Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.
Setting: Forty-four referral centers in seven countries.
Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.
Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.
Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.
Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?
Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.
Setting: Forty-four referral centers in seven countries.
Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.
Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.
Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.
Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
Simplified HOSPITAL score predicts 30-day readmissions
Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?
Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.
Setting: Nine hospitals in four countries.
Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.
This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.
Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.
Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?
Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.
Setting: Nine hospitals in four countries.
Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.
This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.
Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.
Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?
Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.
Setting: Nine hospitals in four countries.
Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.
This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.
Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.
Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.
Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.
How to reduce NICU transfers for asymptomatic hypoglycemia
NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.
Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.
Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.
To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).
Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.
Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.
Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.
Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.
NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.
Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.
Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.
To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).
Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.
Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.
Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.
Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.
NASHVILLE, TENN. – At the University of North Carolina at Chapel Hill, many infants who would previously have been transferred to the NICU for asymptomatic hypoglycemia now are staying with their moms, thanks to a new protocol that holds off on blood glucose testing until infants are fed for the first time and glucose homeostasis can begin.
Not too long ago, the university realized it had a problem that’s probably familiar to other institutions: Its system to monitor newborns at risk for hypoglycemia – those born to diabetic mothers, or who are small or large for gestational age – put too many infants with asymptomatic hypoglycemia into the NICU when they didn’t really need to be there.
Nurse practitioners “were tired of transferring babies they felt were responsive to feeding and did not actually require NICU care,” and “a growing number of families were unhappy with being separated from infants that were well-appearing and feeding well at a time when moms were trying to establish breast feeding and bonding. There was frustration with our protocol,” which “seemed rigid and outdated,” said Ashley Sutton, MD, a pediatric hospitalist at the university.
To fix the problem, Dr. Sutton and others on a multidisciplinary team implemented the American Academy of Pediatrics’ 2011 guidelines for monitoring glucose homeostasis in late-preterm and term newborns at-risk for hypoglycemia, with an additional mandate to initiate immediate, continual skin-to-skin contact at delivery (Pediatrics. 2011 Mar;127[3]:575-9).
Under the new system, children are fed with either their mom’s or a donor’s breast milk within an hour of birth, and the initial glucose check comes at 90 minutes; infants are transferred if blood glucose remains below 25 mg/dL after the second feeding. After 4 hours of life, glucose levels below 35 mg/dL trigger an evaluation for symptoms, not necessarily an automatic NICU transfer.
Labor and delivery nurses also are empowered “to immediately feed the baby no matter what number [they are] seeing,” Dr. Sutton said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The efforts have made a difference. The transfer rate for at-risk infants has fallen from 17% to 3%, and skin-to-skin contact is initiated within the first hour of life in 64%, up from 45%. Feeding of at-risk infants within the first hour has increased from 43% to 61%, and the first glucose check comes at an average of 97 minutes. The number of unnecessary NICU transfers of at-risk infants has fallen sharply.
Meanwhile, there’s been no increase in sepsis evaluations, adverse events, readmissions, and the rates of symptomatic hypoglycemia.
Dr. Sutton and her colleagues had no industry disclosures. The work was funded by the National Institutes of Health.
AT PHM 2017
Key clinical point:
Major finding: After making that and other changes, the transfer rate for at-risk infants at a major academic center fell from 17% to 3%, without an increase in rates of symptomatic hypoglycemia and adverse events.
Data source: Quality improvement project at the University of North Carolina at Chapel Hill.
Disclosures: The investigators had no financial disclosures. The work was funded by the National Institutes of Health.
VIDEO: Rivaroxaban plus aspirin cut cardiovascular events in stable patients
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The dual regimen reduced the combined rate of cardiovascular disease events by 24%, compared with aspirin alone.
Data source: COMPASS is a multicenter, randomized controlled trial with 27,395 patients.
Disclosures: COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
Sneak Peek: The Hospital Leader blog - Aug. 2017 “A Conversation with Dr. Eric Howell”
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Forgo supplemental oxygen in adequately perfused patients with acute MI, study suggests
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
FROM THE ESC CONGRESS 2017
Key clinical point: Supplemental oxygen did not benefit patients with suspected myocardial infarction who did not have hypoxemia.
Major finding: At 1 year, rates of all-cause mortality were 5% among patients who received supplemental oxygen and 5.1% among those who received no oxygen.
Data source: A registry-based, randomized clinical trial of 6,629 patients with suspected myocardial infarction without hypoxemia.
Disclosures: The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
Rapid AMI rule out
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Undiagnosed AF common in higher-risk patients
Over an 18-month period, small, insertable cardiac monitors detected atrial fibrillation in 29% of previously undiagnosed patients who were at high risk of both AF and stroke, and in 40% of patients over 30 months, according to investigators. The study was presented at the annual congress of the European Society of Cardiology and simultaneously published in JAMA Cardiology.
More than half (56%) of patients consequently started oral anticoagulation therapy, noted James A. Reiffel, MD, of Columbia University College of Physicians and Surgeons, New York, with his associates, for the REVEAL AF investigators.
“The incidence of previously undiagnosed atrial fibrillation may be substantial in patients with risk factors for AF and stroke,” they concluded. “Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted.”
Atrial fibrillation affects millions worldwide and is associated with older age, hypertension, diabetes, and heart failure, all of which also independently increase the risk of stroke. Minimally invasive prolonged electrocardiographic monitoring with insertable cardiac monitors might help hasten detection and treatment of AF, but diagnostic yield in high-risk patients has been unclear.
In this single-arm, multicenter, prospective study, researchers inserted Reveal XT or Reveal LINQ (Medtronic) cardiac monitors in 385 adults who had either CHAD2 scores of 3, or CHAD2 scores of 2 and one additional risk factor for AF, such as coronary artery disease, sleep apnea, chronic obstructive pulmonary disease, or renal insufficiency. The primary endpoint was AF lasting at least 6 minutes (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3180). Median follow-up time was 22.5 months. Rates of detecting AF were 6% at 30 days compared with 20% at 6 months, 27% at 12 months, 34% at 24 months, and 40% at 30 months. Patients typically had their first AF episode about 4 months (median, 123 days) after the device was inserted. Among patients who had experienced AF by 18 months, 10% had one or more episodes lasting at least 24 hours, and 72 (56%) were prescribed oral anticoagulation therapy.
The recent PREDATE AF and ASSERT-II studies also found that previously undiagnosed AF was common among high-risk patients, the researchers noted. However, whether anticoagulating patients who have only brief episodes of AF significantly reduces their risk of stroke remains unclear, they added. Three trials (ARTESiA, NOAH, and LOOP) are underway to assess whether oral anticoagulation therapy improves outcomes in patients with device-detected AF.
Medtronic funded the study. Dr. Reiffel and five coinvestigators disclosed consulting for and receiving “modest honoraria” from Medtronic. Two other coinvestigators reported employment with and stock ownership in Medtronic.
The availability of safe and effective oral anticoagulant therapy makes the findings of REVEAL AF highly relevant. This high rate of incident AF makes ICM-based screenings of high-risk individuals a potentially attractive stroke prevention strategy. More detailed subgroup analyses may help identify a patient population with an even higher risk of developing AF. It is also conceivable that this population could have a sufficiently high risk of AF and stroke that a strategy of empiric oral anticoagulation, without the need for AF monitoring, could prove beneficial.
The REVEAL AF study has shown that AF is extremely common among older individuals with stroke risk factors. Over the next 3-4 years, subgroup analyses, economic evaluations, and randomized clinical trials will help determine if this insight can be translated into a cost-effective stroke prevention strategy for high-risk individuals.
Jeff S. Healey, MD, MSc, is at the Population Health Research Institute, McMaster University, Hamilton, Ont. He is the principal investigator of the ASSERT-II and ARTESiA trials, and had no other relevant disclosures. These comments are from his editorial (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3203).
The availability of safe and effective oral anticoagulant therapy makes the findings of REVEAL AF highly relevant. This high rate of incident AF makes ICM-based screenings of high-risk individuals a potentially attractive stroke prevention strategy. More detailed subgroup analyses may help identify a patient population with an even higher risk of developing AF. It is also conceivable that this population could have a sufficiently high risk of AF and stroke that a strategy of empiric oral anticoagulation, without the need for AF monitoring, could prove beneficial.
The REVEAL AF study has shown that AF is extremely common among older individuals with stroke risk factors. Over the next 3-4 years, subgroup analyses, economic evaluations, and randomized clinical trials will help determine if this insight can be translated into a cost-effective stroke prevention strategy for high-risk individuals.
Jeff S. Healey, MD, MSc, is at the Population Health Research Institute, McMaster University, Hamilton, Ont. He is the principal investigator of the ASSERT-II and ARTESiA trials, and had no other relevant disclosures. These comments are from his editorial (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3203).
The availability of safe and effective oral anticoagulant therapy makes the findings of REVEAL AF highly relevant. This high rate of incident AF makes ICM-based screenings of high-risk individuals a potentially attractive stroke prevention strategy. More detailed subgroup analyses may help identify a patient population with an even higher risk of developing AF. It is also conceivable that this population could have a sufficiently high risk of AF and stroke that a strategy of empiric oral anticoagulation, without the need for AF monitoring, could prove beneficial.
The REVEAL AF study has shown that AF is extremely common among older individuals with stroke risk factors. Over the next 3-4 years, subgroup analyses, economic evaluations, and randomized clinical trials will help determine if this insight can be translated into a cost-effective stroke prevention strategy for high-risk individuals.
Jeff S. Healey, MD, MSc, is at the Population Health Research Institute, McMaster University, Hamilton, Ont. He is the principal investigator of the ASSERT-II and ARTESiA trials, and had no other relevant disclosures. These comments are from his editorial (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3203).
Over an 18-month period, small, insertable cardiac monitors detected atrial fibrillation in 29% of previously undiagnosed patients who were at high risk of both AF and stroke, and in 40% of patients over 30 months, according to investigators. The study was presented at the annual congress of the European Society of Cardiology and simultaneously published in JAMA Cardiology.
More than half (56%) of patients consequently started oral anticoagulation therapy, noted James A. Reiffel, MD, of Columbia University College of Physicians and Surgeons, New York, with his associates, for the REVEAL AF investigators.
“The incidence of previously undiagnosed atrial fibrillation may be substantial in patients with risk factors for AF and stroke,” they concluded. “Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted.”
Atrial fibrillation affects millions worldwide and is associated with older age, hypertension, diabetes, and heart failure, all of which also independently increase the risk of stroke. Minimally invasive prolonged electrocardiographic monitoring with insertable cardiac monitors might help hasten detection and treatment of AF, but diagnostic yield in high-risk patients has been unclear.
In this single-arm, multicenter, prospective study, researchers inserted Reveal XT or Reveal LINQ (Medtronic) cardiac monitors in 385 adults who had either CHAD2 scores of 3, or CHAD2 scores of 2 and one additional risk factor for AF, such as coronary artery disease, sleep apnea, chronic obstructive pulmonary disease, or renal insufficiency. The primary endpoint was AF lasting at least 6 minutes (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3180). Median follow-up time was 22.5 months. Rates of detecting AF were 6% at 30 days compared with 20% at 6 months, 27% at 12 months, 34% at 24 months, and 40% at 30 months. Patients typically had their first AF episode about 4 months (median, 123 days) after the device was inserted. Among patients who had experienced AF by 18 months, 10% had one or more episodes lasting at least 24 hours, and 72 (56%) were prescribed oral anticoagulation therapy.
The recent PREDATE AF and ASSERT-II studies also found that previously undiagnosed AF was common among high-risk patients, the researchers noted. However, whether anticoagulating patients who have only brief episodes of AF significantly reduces their risk of stroke remains unclear, they added. Three trials (ARTESiA, NOAH, and LOOP) are underway to assess whether oral anticoagulation therapy improves outcomes in patients with device-detected AF.
Medtronic funded the study. Dr. Reiffel and five coinvestigators disclosed consulting for and receiving “modest honoraria” from Medtronic. Two other coinvestigators reported employment with and stock ownership in Medtronic.
Over an 18-month period, small, insertable cardiac monitors detected atrial fibrillation in 29% of previously undiagnosed patients who were at high risk of both AF and stroke, and in 40% of patients over 30 months, according to investigators. The study was presented at the annual congress of the European Society of Cardiology and simultaneously published in JAMA Cardiology.
More than half (56%) of patients consequently started oral anticoagulation therapy, noted James A. Reiffel, MD, of Columbia University College of Physicians and Surgeons, New York, with his associates, for the REVEAL AF investigators.
“The incidence of previously undiagnosed atrial fibrillation may be substantial in patients with risk factors for AF and stroke,” they concluded. “Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted.”
Atrial fibrillation affects millions worldwide and is associated with older age, hypertension, diabetes, and heart failure, all of which also independently increase the risk of stroke. Minimally invasive prolonged electrocardiographic monitoring with insertable cardiac monitors might help hasten detection and treatment of AF, but diagnostic yield in high-risk patients has been unclear.
In this single-arm, multicenter, prospective study, researchers inserted Reveal XT or Reveal LINQ (Medtronic) cardiac monitors in 385 adults who had either CHAD2 scores of 3, or CHAD2 scores of 2 and one additional risk factor for AF, such as coronary artery disease, sleep apnea, chronic obstructive pulmonary disease, or renal insufficiency. The primary endpoint was AF lasting at least 6 minutes (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3180). Median follow-up time was 22.5 months. Rates of detecting AF were 6% at 30 days compared with 20% at 6 months, 27% at 12 months, 34% at 24 months, and 40% at 30 months. Patients typically had their first AF episode about 4 months (median, 123 days) after the device was inserted. Among patients who had experienced AF by 18 months, 10% had one or more episodes lasting at least 24 hours, and 72 (56%) were prescribed oral anticoagulation therapy.
The recent PREDATE AF and ASSERT-II studies also found that previously undiagnosed AF was common among high-risk patients, the researchers noted. However, whether anticoagulating patients who have only brief episodes of AF significantly reduces their risk of stroke remains unclear, they added. Three trials (ARTESiA, NOAH, and LOOP) are underway to assess whether oral anticoagulation therapy improves outcomes in patients with device-detected AF.
Medtronic funded the study. Dr. Reiffel and five coinvestigators disclosed consulting for and receiving “modest honoraria” from Medtronic. Two other coinvestigators reported employment with and stock ownership in Medtronic.
FROM THE ESC CONGRESS 2017
Key clinical point: Undiagnosed atrial fibrillation is common in high-risk patients.
Major finding: At 18 months, 29% of previously undiagnosed, high-risk patients had experienced atrial fibrillation lasting 6 or more minutes.
Data source: A single-arm, prospective, multicenter study of 446 patients with a CHADS2 score of at least 3, or a CHADS2 score of at least 2 plus at least one other risk factor (coronary artery disease, sleep apnea, chronic obstructive pulmonary disease, or renal insufficiency).
Disclosures: Medtronic funded the study. Dr. Reiffel and five coinvestigators disclosed consulting for and receiving “modest honoraria” from Medtronic. Two other coinvestigators reported employment with and stock ownership in Medtronic.