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Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m² for 90 days with a final rate of at least 30 mL/min/1.73 m². Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

[email protected]

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

[email protected]

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

[email protected]

Background: With increased use of anticoagulants, the amount of related ADEs has also increased. ADEs may be preventable through improved communication during transitions of care. The key communication elements are not standardized.

The following items are the 15 RDEs that require documentation: (1) current anticoagulants; (2) indications; (3) new or previous user; (4) if new, start date, (5) short-term or long-term use; (6) if short term, intended duration; (7) last two doses given; (8) next dose due; (9) latest renal function; (10) provision of patient education materials; (11) assessment of patient/caregiver understanding; (12) future anticoagulation provider; and if warfarin, (13) the target range, (14) at least 2-3 consecutive international normalized ratio results, and (15) next INR level.

Bottom line: Standardized communication during transitions of care regarding anticoagulation may reduce anticoagulant ADEs. Objective evidence showing reduction of ADEs after implementation of the list is needed.

Citation: Triller D et al. Defining minimum necessary anticoagulation-related communication at discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition. Jt Comm J Qual Patient Saf. 2018;44(11):630-40.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: With increased use of anticoagulants, the amount of related ADEs has also increased. ADEs may be preventable through improved communication during transitions of care. The key communication elements are not standardized.

The following items are the 15 RDEs that require documentation: (1) current anticoagulants; (2) indications; (3) new or previous user; (4) if new, start date, (5) short-term or long-term use; (6) if short term, intended duration; (7) last two doses given; (8) next dose due; (9) latest renal function; (10) provision of patient education materials; (11) assessment of patient/caregiver understanding; (12) future anticoagulation provider; and if warfarin, (13) the target range, (14) at least 2-3 consecutive international normalized ratio results, and (15) next INR level.

Bottom line: Standardized communication during transitions of care regarding anticoagulation may reduce anticoagulant ADEs. Objective evidence showing reduction of ADEs after implementation of the list is needed.

Citation: Triller D et al. Defining minimum necessary anticoagulation-related communication at discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition. Jt Comm J Qual Patient Saf. 2018;44(11):630-40.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: With increased use of anticoagulants, the amount of related ADEs has also increased. ADEs may be preventable through improved communication during transitions of care. The key communication elements are not standardized.

The following items are the 15 RDEs that require documentation: (1) current anticoagulants; (2) indications; (3) new or previous user; (4) if new, start date, (5) short-term or long-term use; (6) if short term, intended duration; (7) last two doses given; (8) next dose due; (9) latest renal function; (10) provision of patient education materials; (11) assessment of patient/caregiver understanding; (12) future anticoagulation provider; and if warfarin, (13) the target range, (14) at least 2-3 consecutive international normalized ratio results, and (15) next INR level.

Bottom line: Standardized communication during transitions of care regarding anticoagulation may reduce anticoagulant ADEs. Objective evidence showing reduction of ADEs after implementation of the list is needed.

Citation: Triller D et al. Defining minimum necessary anticoagulation-related communication at discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition. Jt Comm J Qual Patient Saf. 2018;44(11):630-40.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

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Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)