Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

A lawsuit recently levied against a hospital accused of discharging a homeless patient to city streets serves as a reminder that physicians need to look beyond a patient's immediate health concerns when considering care transitions, one hospitalist says.

As reported in the Los Angeles Times, Glendale Adventist Medical Center in Glendale, Calif., has agreed to pay $700,000 in civil penalties to settle a lawsuit brought against it by the Los Angeles City Attorney. A hospital spokesperson said the medical center denies the charges but has agreed to pay the fine to avoid the cost of fighting the allegations.

"We have to be able to recognize that just writing a discharge order is not meeting any of our patients' needs," says Gregory Misky, MD, hospitalist and associate professor of medicine at the University of Colorado (UC) Hospital in Denver. "It's hard to expect we can fix their COPD or manage their diabetes when there are all these layers of social and behavioral health needs."

Dr. Misky says he gradually became interested in issues affecting indigent patients while researching ways to help patients transition from hospital to home.

"Some patients are dealing with financial issues," he says. "Some have acute family crises they're dealing with. Some have homelessness issues or housing issues. All those things interfere with their health and ability to prioritize health needs over these other things."

One of Dr. Misky's current research projects involves performing qualitative interviews with patients who are readmitted within 30 days to learn what challenges they dealt with after being discharged.

As for "patient dumping," Dr. Misky says that, in his experience, hospitals typically do the opposite: hospitalize patients for indefinite periods of time when they seem to have no family to turn to, for example, or are dealing with cognitive issues.

Here are Dr. Misky's tips for providing better discharges:

• Be aware: Not all patients are equal. It's important to realize patients may not recuperate from pneumonia if they are living on the street;
• Rely on case managers: Hospitalists at the UC Hospital perform discharge rounds with a team that includes a case manager, who is usually a registered nurse or social worker. Let the case manager know about your patients’ needs; and
• Form partnerships: Learn about how you can match up your patients with resources for homeless people available in your community.

A lawsuit recently levied against a hospital accused of discharging a homeless patient to city streets serves as a reminder that physicians need to look beyond a patient's immediate health concerns when considering care transitions, one hospitalist says.

As reported in the Los Angeles Times, Glendale Adventist Medical Center in Glendale, Calif., has agreed to pay $700,000 in civil penalties to settle a lawsuit brought against it by the Los Angeles City Attorney. A hospital spokesperson said the medical center denies the charges but has agreed to pay the fine to avoid the cost of fighting the allegations.

"We have to be able to recognize that just writing a discharge order is not meeting any of our patients' needs," says Gregory Misky, MD, hospitalist and associate professor of medicine at the University of Colorado (UC) Hospital in Denver. "It's hard to expect we can fix their COPD or manage their diabetes when there are all these layers of social and behavioral health needs."

Dr. Misky says he gradually became interested in issues affecting indigent patients while researching ways to help patients transition from hospital to home.

"Some patients are dealing with financial issues," he says. "Some have acute family crises they're dealing with. Some have homelessness issues or housing issues. All those things interfere with their health and ability to prioritize health needs over these other things."

One of Dr. Misky's current research projects involves performing qualitative interviews with patients who are readmitted within 30 days to learn what challenges they dealt with after being discharged.

As for "patient dumping," Dr. Misky says that, in his experience, hospitals typically do the opposite: hospitalize patients for indefinite periods of time when they seem to have no family to turn to, for example, or are dealing with cognitive issues.

Here are Dr. Misky's tips for providing better discharges:

• Be aware: Not all patients are equal. It's important to realize patients may not recuperate from pneumonia if they are living on the street;
• Rely on case managers: Hospitalists at the UC Hospital perform discharge rounds with a team that includes a case manager, who is usually a registered nurse or social worker. Let the case manager know about your patients’ needs; and
• Form partnerships: Learn about how you can match up your patients with resources for homeless people available in your community.

A lawsuit recently levied against a hospital accused of discharging a homeless patient to city streets serves as a reminder that physicians need to look beyond a patient's immediate health concerns when considering care transitions, one hospitalist says.

As reported in the Los Angeles Times, Glendale Adventist Medical Center in Glendale, Calif., has agreed to pay $700,000 in civil penalties to settle a lawsuit brought against it by the Los Angeles City Attorney. A hospital spokesperson said the medical center denies the charges but has agreed to pay the fine to avoid the cost of fighting the allegations.

"We have to be able to recognize that just writing a discharge order is not meeting any of our patients' needs," says Gregory Misky, MD, hospitalist and associate professor of medicine at the University of Colorado (UC) Hospital in Denver. "It's hard to expect we can fix their COPD or manage their diabetes when there are all these layers of social and behavioral health needs."

Dr. Misky says he gradually became interested in issues affecting indigent patients while researching ways to help patients transition from hospital to home.

"Some patients are dealing with financial issues," he says. "Some have acute family crises they're dealing with. Some have homelessness issues or housing issues. All those things interfere with their health and ability to prioritize health needs over these other things."

One of Dr. Misky's current research projects involves performing qualitative interviews with patients who are readmitted within 30 days to learn what challenges they dealt with after being discharged.

As for "patient dumping," Dr. Misky says that, in his experience, hospitals typically do the opposite: hospitalize patients for indefinite periods of time when they seem to have no family to turn to, for example, or are dealing with cognitive issues.

Here are Dr. Misky's tips for providing better discharges:

• Be aware: Not all patients are equal. It's important to realize patients may not recuperate from pneumonia if they are living on the street;
• Rely on case managers: Hospitalists at the UC Hospital perform discharge rounds with a team that includes a case manager, who is usually a registered nurse or social worker. Let the case manager know about your patients’ needs; and
• Form partnerships: Learn about how you can match up your patients with resources for homeless people available in your community.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.