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SAN DIEGO – The wider picture of the patient’s health and prognosis, not just chronologic age, should enter into the clinical decision to initiate dialysis, according to Bjorg Thorsteinsdottir, MD, a palliative care physician at the Mayo Clinic in Rochester, Minn.

“People perceive they have no choice [but treatment], and we perceive we have to do things to them until everything is lost, then we expect them to do a 180 [degree turn],” she said in a presentation at the meeting sponsored by the American Society of Nephrology.

“A 90-year-old fit individual, with minimal comorbidity living independently, would absolutely be a good candidate for dialysis, while a 75-year-old patient with bad peripheral vascular disease and dementia, living in a nursing home, would be unlikely to live longer on dialysis than off dialysis,” she said. “We need to weigh the risks and benefits for each individual patient against their goals and values. We need to be honest about the lack of benefit for certain subgroups of patients and the heavy treatment burdens of dialysis. Age, comorbidity, and frailty all factor into these deliberations and prognosis.”

More than 107,000 people over age 75 in the United States received dialysis in 2015, according to statistics gathered by the National Kidney Foundation. Yet the survival advantage of dialysis is more limited in elderly patients with multiple comorbidities, Dr. Thorsteinsdottir said. “It becomes important to think about the harms of treatment.”

A 2016 study from the Netherlands found no survival advantage to dialysis, compared with conservative management among kidney failure patients aged 80 and older. The survival advantage was limited with dialysis in patients aged 70 and older who also had multiple comorbidities. (Clin J Am Soc Nephrol. 2016 Apr;11(4):633-40)

In an interview, Dr. Thorsteinsdottir acknowledged that “determining who is unlikely to benefit from dialysis is complicated.” However, she said, “we know that the following comorbidities are the worst: dementia and peripheral vascular disease.”

“No one that I know of currently has an age cutoff for dialysis,” Dr. Thorsteinsdottir said in the interview, “and I do not believe the U.S. is ready for any kind of explicit limit setting by the government on dialysis treatment.”

“We must respond to legitimate concerns raised by recent studies that suggest that strong moral imperatives – to treat anyone we can treat – have created a situation where we are not pausing and asking hard questions about whether the patient in front of us is likely to benefit from dialysis,” she said in the interview. “Patients sense this and do not feel that they are given any alternatives to dialysis treatment. This needs to change.”

Dr. Thorsteinsdottir reported no relevant financial disclosures.

SAN DIEGO – The wider picture of the patient’s health and prognosis, not just chronologic age, should enter into the clinical decision to initiate dialysis, according to Bjorg Thorsteinsdottir, MD, a palliative care physician at the Mayo Clinic in Rochester, Minn.

“People perceive they have no choice [but treatment], and we perceive we have to do things to them until everything is lost, then we expect them to do a 180 [degree turn],” she said in a presentation at the meeting sponsored by the American Society of Nephrology.

“A 90-year-old fit individual, with minimal comorbidity living independently, would absolutely be a good candidate for dialysis, while a 75-year-old patient with bad peripheral vascular disease and dementia, living in a nursing home, would be unlikely to live longer on dialysis than off dialysis,” she said. “We need to weigh the risks and benefits for each individual patient against their goals and values. We need to be honest about the lack of benefit for certain subgroups of patients and the heavy treatment burdens of dialysis. Age, comorbidity, and frailty all factor into these deliberations and prognosis.”

More than 107,000 people over age 75 in the United States received dialysis in 2015, according to statistics gathered by the National Kidney Foundation. Yet the survival advantage of dialysis is more limited in elderly patients with multiple comorbidities, Dr. Thorsteinsdottir said. “It becomes important to think about the harms of treatment.”

A 2016 study from the Netherlands found no survival advantage to dialysis, compared with conservative management among kidney failure patients aged 80 and older. The survival advantage was limited with dialysis in patients aged 70 and older who also had multiple comorbidities. (Clin J Am Soc Nephrol. 2016 Apr;11(4):633-40)

In an interview, Dr. Thorsteinsdottir acknowledged that “determining who is unlikely to benefit from dialysis is complicated.” However, she said, “we know that the following comorbidities are the worst: dementia and peripheral vascular disease.”

“No one that I know of currently has an age cutoff for dialysis,” Dr. Thorsteinsdottir said in the interview, “and I do not believe the U.S. is ready for any kind of explicit limit setting by the government on dialysis treatment.”

“We must respond to legitimate concerns raised by recent studies that suggest that strong moral imperatives – to treat anyone we can treat – have created a situation where we are not pausing and asking hard questions about whether the patient in front of us is likely to benefit from dialysis,” she said in the interview. “Patients sense this and do not feel that they are given any alternatives to dialysis treatment. This needs to change.”

Dr. Thorsteinsdottir reported no relevant financial disclosures.

SAN DIEGO – The wider picture of the patient’s health and prognosis, not just chronologic age, should enter into the clinical decision to initiate dialysis, according to Bjorg Thorsteinsdottir, MD, a palliative care physician at the Mayo Clinic in Rochester, Minn.

“People perceive they have no choice [but treatment], and we perceive we have to do things to them until everything is lost, then we expect them to do a 180 [degree turn],” she said in a presentation at the meeting sponsored by the American Society of Nephrology.

“A 90-year-old fit individual, with minimal comorbidity living independently, would absolutely be a good candidate for dialysis, while a 75-year-old patient with bad peripheral vascular disease and dementia, living in a nursing home, would be unlikely to live longer on dialysis than off dialysis,” she said. “We need to weigh the risks and benefits for each individual patient against their goals and values. We need to be honest about the lack of benefit for certain subgroups of patients and the heavy treatment burdens of dialysis. Age, comorbidity, and frailty all factor into these deliberations and prognosis.”

More than 107,000 people over age 75 in the United States received dialysis in 2015, according to statistics gathered by the National Kidney Foundation. Yet the survival advantage of dialysis is more limited in elderly patients with multiple comorbidities, Dr. Thorsteinsdottir said. “It becomes important to think about the harms of treatment.”

A 2016 study from the Netherlands found no survival advantage to dialysis, compared with conservative management among kidney failure patients aged 80 and older. The survival advantage was limited with dialysis in patients aged 70 and older who also had multiple comorbidities. (Clin J Am Soc Nephrol. 2016 Apr;11(4):633-40)

In an interview, Dr. Thorsteinsdottir acknowledged that “determining who is unlikely to benefit from dialysis is complicated.” However, she said, “we know that the following comorbidities are the worst: dementia and peripheral vascular disease.”

“No one that I know of currently has an age cutoff for dialysis,” Dr. Thorsteinsdottir said in the interview, “and I do not believe the U.S. is ready for any kind of explicit limit setting by the government on dialysis treatment.”

“We must respond to legitimate concerns raised by recent studies that suggest that strong moral imperatives – to treat anyone we can treat – have created a situation where we are not pausing and asking hard questions about whether the patient in front of us is likely to benefit from dialysis,” she said in the interview. “Patients sense this and do not feel that they are given any alternatives to dialysis treatment. This needs to change.”

Dr. Thorsteinsdottir reported no relevant financial disclosures.

CHICAGO – Initiation of angiotensin-neprilysin inhibition using sacubitril/valsartan during hospitalization for acute decompensated heart failure, instead of relying upon enalapril, resulted in a substantially greater reduction in N-terminal of the prohormone brain natriuretic peptide concentration and a markedly lower rate of rehospitalization with no safety downside in the PIONEER-HF trial, Eric J. Velazquez, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“We believe these results have clinical implications that support the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure and reduced ejection fraction irrespective of prior ACE inhibitor or ARB [angiotensin II receptor blocker] use or prior diagnosis of heart failure,” said Dr. Velazquez, a professor of medicine and chief of the section of cardiovascular medicine at Yale University, New Haven, Conn., and physician in chief of the Heart and Vascular Center for the Yale-New Haven Health System.

Sacubitril/valsartan (Entresto) has a class I indication for treatment of symptomatic heart failure with reduced ejection fraction (HFrEF) in the AHA/American College of Cardiology guidelines. This strong recommendation is based largely upon the impressive results of the PARADIGM-HF trial, which in ambulatory outpatients demonstrated a lower risk of cardiovascular mortality or hospitalization for heart failure than enalapril (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

However, since patients with acute decompensated heart failure (ADHF) were excluded from PARADIGM-HF, the safety and effectiveness of starting such patients on the drug while hospitalized for acute decompensation was unknown.

PIONEER-HF was carried out to shed light on that issue and thereby address a major unmet need for better treatments for ADHF. Even though this condition accounts for more than 1 million hospitalizations annually in the United States, short-term rehospitalization and mortality rates in affected patients remain unacceptably high at 21% and 12%, respectively. And the standard-of-care treatment – decongestion with intravenous diuretics and hemodynamic support with inotropes and vasodilators – hasn’t changed in nearly half a century, Dr. Velazquez noted.

The trial included 881 patients hospitalized for acute decompensated HFrEF at 129 U.S. centers. The study population was diverse: 36% of participants were black and one-third of subjects had no diagnosis of heart failure prior to their hospitalization. After achieving hemodynamic stabilization, patients were randomized to receive sacubitril/valsartan or enalapril.

Key outcomes

The primary endpoint was change in N-terminal of the prohormone brain natriuretic peptide concentration from baseline to week 8. There was a 25% reduction in the enalapril group and a 45% reduction with sacubitril/valsartan. This translated to a highly significant 29% greater relative risk reduction with sacubitril/valsartan.

More eye opening was the between-group difference in the prespecified composite clinical endpoint comprising death, rehospitalization for heart failure, implantation of a left ventricular assist device, or listing for heart transplant during the 8-week study.

The rate was 16.8% in the enalapril group and 9.3% with sacubitril/valsartan. This worked out to a 46% relative risk reduction, with a number needed to treat of 13.

The composite result was driven by a 44% reduction in risk of heart failure rehospitalization in the sacubitril/valsartan group: 8.0% versus 13.8%. The sacubitril/valsartan group also had a numerically lower mortality rate: 2.3% versus 3.4%, although the number of fatalities was small and this 34% relative risk reduction didn’t achieve statistical significance.

Rates of the key safety outcomes – symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema – didn’t differ between the two study arms. Of interest, however, all six cases of angioedema in the enalapril group occurred in black patients, while the only case in the sacubitril/valsartan group was in a white patient.

PIONEER-HF treatment strategy

Hemodynamic stabilization as a prelude to randomization to sacubitril/valsartan or enalapril required maintaining a systolic blood pressure of at least 100 mm Hg in the previous 6 hours, with no symptomatic hypotension, intensification of intravenous diuretics, or use of intravenous vasodilators during that time period, and no intravenous inotropes in the previous 24 hours.

Enalapril was titrated to a target dose of 10 mg twice daily. Sacubitril/valsartan was titrated to a target dose of 97/103 mg twice daily. Titration was carried out using an algorithm based upon systolic BP. If the SBP was at least 100 and less than 120 mm Hg at baseline, sacubitril/valsartan was initiated at 24/26 mg twice daily, enalapril at 2.5 mg b.i.d. If the SBP at randomization was 120 mm Hg or higher, the initial dosing was sacubitril/valsartan at 49/51 mm Hg b.i.d. or enalapril at 5 mg b.i.d. Up-titration occurred after 1 week, then biweekly through week 8.

PIONEER in perspective

Bruce Jancin/MDedge News

Discussant Larry A. Allen, MD, a heart failure specialist at the University of Colorado at Denver, Aurora, predicted that this will be a practice-changing study.

“There has been a need for a study like PIONEER in heart failure,” he observed. While multiple randomized trials have advanced the treatment of ambulatory HFrEF patients, demonstrating benefit for initiation and intensification of treatment with ACE inhibitors, angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, the treatment of patients with ADHF has remained relatively static, marked by failed trials of once-promising novel agents including tolvaptan, nesiritide, and serelaxin.

“All the data is in ambulatory patients, but the action for the care of heart failure patients actually occurs largely in the hospital. Seventy percent of care provided in the U.S. to patients with heart failure occurs in the hospital setting. These patients are a captive audience at that time, and the transitions from inpatient to outpatient care are fragile,” Dr. Allen said.

He noted that the use of sacubitril/valsartan in routine practice as reflected in national registries has been “extremely low” – less than 15% among eligible patients – despite the drug having been approved more than 3 years ago. One major reason for the low uptake, in his view, is clinical inertia. That should melt away in what he termed “the post-PIONEER world.”

“I think one of the great things about this study is it keeps it simple. We now have a simpler algorithm for inpatient and subsequent outpatient management of heart failure with reduced ejection fraction. It’s easier for us to start with the treatment we want patients to be on, and it’s better for patients, too. Most importantly, this study reinforces the importance and safety of aggressive guideline-directed medical therapy starting from the beginning in most patients,” Dr. Allen said.

The study findings were published simultaneously in the New England Journal of Medicine (2018 Nov 11. doi: 10.1056/NEJMoa1812851).

PIONEER-HF was sponsored by Novartis. Dr. Velazquez reported receiving research grants from and serving as a consultant to that company and others. Dr. Allen reported having no financial conflicts.

[email protected]

CHICAGO – Initiation of angiotensin-neprilysin inhibition using sacubitril/valsartan during hospitalization for acute decompensated heart failure, instead of relying upon enalapril, resulted in a substantially greater reduction in N-terminal of the prohormone brain natriuretic peptide concentration and a markedly lower rate of rehospitalization with no safety downside in the PIONEER-HF trial, Eric J. Velazquez, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“We believe these results have clinical implications that support the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure and reduced ejection fraction irrespective of prior ACE inhibitor or ARB [angiotensin II receptor blocker] use or prior diagnosis of heart failure,” said Dr. Velazquez, a professor of medicine and chief of the section of cardiovascular medicine at Yale University, New Haven, Conn., and physician in chief of the Heart and Vascular Center for the Yale-New Haven Health System.

Sacubitril/valsartan (Entresto) has a class I indication for treatment of symptomatic heart failure with reduced ejection fraction (HFrEF) in the AHA/American College of Cardiology guidelines. This strong recommendation is based largely upon the impressive results of the PARADIGM-HF trial, which in ambulatory outpatients demonstrated a lower risk of cardiovascular mortality or hospitalization for heart failure than enalapril (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

However, since patients with acute decompensated heart failure (ADHF) were excluded from PARADIGM-HF, the safety and effectiveness of starting such patients on the drug while hospitalized for acute decompensation was unknown.

PIONEER-HF was carried out to shed light on that issue and thereby address a major unmet need for better treatments for ADHF. Even though this condition accounts for more than 1 million hospitalizations annually in the United States, short-term rehospitalization and mortality rates in affected patients remain unacceptably high at 21% and 12%, respectively. And the standard-of-care treatment – decongestion with intravenous diuretics and hemodynamic support with inotropes and vasodilators – hasn’t changed in nearly half a century, Dr. Velazquez noted.

The trial included 881 patients hospitalized for acute decompensated HFrEF at 129 U.S. centers. The study population was diverse: 36% of participants were black and one-third of subjects had no diagnosis of heart failure prior to their hospitalization. After achieving hemodynamic stabilization, patients were randomized to receive sacubitril/valsartan or enalapril.

Key outcomes

The primary endpoint was change in N-terminal of the prohormone brain natriuretic peptide concentration from baseline to week 8. There was a 25% reduction in the enalapril group and a 45% reduction with sacubitril/valsartan. This translated to a highly significant 29% greater relative risk reduction with sacubitril/valsartan.

More eye opening was the between-group difference in the prespecified composite clinical endpoint comprising death, rehospitalization for heart failure, implantation of a left ventricular assist device, or listing for heart transplant during the 8-week study.

The rate was 16.8% in the enalapril group and 9.3% with sacubitril/valsartan. This worked out to a 46% relative risk reduction, with a number needed to treat of 13.

The composite result was driven by a 44% reduction in risk of heart failure rehospitalization in the sacubitril/valsartan group: 8.0% versus 13.8%. The sacubitril/valsartan group also had a numerically lower mortality rate: 2.3% versus 3.4%, although the number of fatalities was small and this 34% relative risk reduction didn’t achieve statistical significance.

Rates of the key safety outcomes – symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema – didn’t differ between the two study arms. Of interest, however, all six cases of angioedema in the enalapril group occurred in black patients, while the only case in the sacubitril/valsartan group was in a white patient.

PIONEER-HF treatment strategy

Hemodynamic stabilization as a prelude to randomization to sacubitril/valsartan or enalapril required maintaining a systolic blood pressure of at least 100 mm Hg in the previous 6 hours, with no symptomatic hypotension, intensification of intravenous diuretics, or use of intravenous vasodilators during that time period, and no intravenous inotropes in the previous 24 hours.

Enalapril was titrated to a target dose of 10 mg twice daily. Sacubitril/valsartan was titrated to a target dose of 97/103 mg twice daily. Titration was carried out using an algorithm based upon systolic BP. If the SBP was at least 100 and less than 120 mm Hg at baseline, sacubitril/valsartan was initiated at 24/26 mg twice daily, enalapril at 2.5 mg b.i.d. If the SBP at randomization was 120 mm Hg or higher, the initial dosing was sacubitril/valsartan at 49/51 mm Hg b.i.d. or enalapril at 5 mg b.i.d. Up-titration occurred after 1 week, then biweekly through week 8.

PIONEER in perspective

Bruce Jancin/MDedge News

Discussant Larry A. Allen, MD, a heart failure specialist at the University of Colorado at Denver, Aurora, predicted that this will be a practice-changing study.

“There has been a need for a study like PIONEER in heart failure,” he observed. While multiple randomized trials have advanced the treatment of ambulatory HFrEF patients, demonstrating benefit for initiation and intensification of treatment with ACE inhibitors, angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, the treatment of patients with ADHF has remained relatively static, marked by failed trials of once-promising novel agents including tolvaptan, nesiritide, and serelaxin.

“All the data is in ambulatory patients, but the action for the care of heart failure patients actually occurs largely in the hospital. Seventy percent of care provided in the U.S. to patients with heart failure occurs in the hospital setting. These patients are a captive audience at that time, and the transitions from inpatient to outpatient care are fragile,” Dr. Allen said.

He noted that the use of sacubitril/valsartan in routine practice as reflected in national registries has been “extremely low” – less than 15% among eligible patients – despite the drug having been approved more than 3 years ago. One major reason for the low uptake, in his view, is clinical inertia. That should melt away in what he termed “the post-PIONEER world.”

“I think one of the great things about this study is it keeps it simple. We now have a simpler algorithm for inpatient and subsequent outpatient management of heart failure with reduced ejection fraction. It’s easier for us to start with the treatment we want patients to be on, and it’s better for patients, too. Most importantly, this study reinforces the importance and safety of aggressive guideline-directed medical therapy starting from the beginning in most patients,” Dr. Allen said.

The study findings were published simultaneously in the New England Journal of Medicine (2018 Nov 11. doi: 10.1056/NEJMoa1812851).

PIONEER-HF was sponsored by Novartis. Dr. Velazquez reported receiving research grants from and serving as a consultant to that company and others. Dr. Allen reported having no financial conflicts.

[email protected]

CHICAGO – Initiation of angiotensin-neprilysin inhibition using sacubitril/valsartan during hospitalization for acute decompensated heart failure, instead of relying upon enalapril, resulted in a substantially greater reduction in N-terminal of the prohormone brain natriuretic peptide concentration and a markedly lower rate of rehospitalization with no safety downside in the PIONEER-HF trial, Eric J. Velazquez, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“We believe these results have clinical implications that support the in-hospital initiation of sacubitril/valsartan in stabilized patients with acute decompensated heart failure and reduced ejection fraction irrespective of prior ACE inhibitor or ARB [angiotensin II receptor blocker] use or prior diagnosis of heart failure,” said Dr. Velazquez, a professor of medicine and chief of the section of cardiovascular medicine at Yale University, New Haven, Conn., and physician in chief of the Heart and Vascular Center for the Yale-New Haven Health System.

Sacubitril/valsartan (Entresto) has a class I indication for treatment of symptomatic heart failure with reduced ejection fraction (HFrEF) in the AHA/American College of Cardiology guidelines. This strong recommendation is based largely upon the impressive results of the PARADIGM-HF trial, which in ambulatory outpatients demonstrated a lower risk of cardiovascular mortality or hospitalization for heart failure than enalapril (N Engl J Med. 2014 Sep 11;371[11]:993-1004).

However, since patients with acute decompensated heart failure (ADHF) were excluded from PARADIGM-HF, the safety and effectiveness of starting such patients on the drug while hospitalized for acute decompensation was unknown.

PIONEER-HF was carried out to shed light on that issue and thereby address a major unmet need for better treatments for ADHF. Even though this condition accounts for more than 1 million hospitalizations annually in the United States, short-term rehospitalization and mortality rates in affected patients remain unacceptably high at 21% and 12%, respectively. And the standard-of-care treatment – decongestion with intravenous diuretics and hemodynamic support with inotropes and vasodilators – hasn’t changed in nearly half a century, Dr. Velazquez noted.

The trial included 881 patients hospitalized for acute decompensated HFrEF at 129 U.S. centers. The study population was diverse: 36% of participants were black and one-third of subjects had no diagnosis of heart failure prior to their hospitalization. After achieving hemodynamic stabilization, patients were randomized to receive sacubitril/valsartan or enalapril.

Key outcomes

The primary endpoint was change in N-terminal of the prohormone brain natriuretic peptide concentration from baseline to week 8. There was a 25% reduction in the enalapril group and a 45% reduction with sacubitril/valsartan. This translated to a highly significant 29% greater relative risk reduction with sacubitril/valsartan.

More eye opening was the between-group difference in the prespecified composite clinical endpoint comprising death, rehospitalization for heart failure, implantation of a left ventricular assist device, or listing for heart transplant during the 8-week study.

The rate was 16.8% in the enalapril group and 9.3% with sacubitril/valsartan. This worked out to a 46% relative risk reduction, with a number needed to treat of 13.

The composite result was driven by a 44% reduction in risk of heart failure rehospitalization in the sacubitril/valsartan group: 8.0% versus 13.8%. The sacubitril/valsartan group also had a numerically lower mortality rate: 2.3% versus 3.4%, although the number of fatalities was small and this 34% relative risk reduction didn’t achieve statistical significance.

Rates of the key safety outcomes – symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema – didn’t differ between the two study arms. Of interest, however, all six cases of angioedema in the enalapril group occurred in black patients, while the only case in the sacubitril/valsartan group was in a white patient.

PIONEER-HF treatment strategy

Hemodynamic stabilization as a prelude to randomization to sacubitril/valsartan or enalapril required maintaining a systolic blood pressure of at least 100 mm Hg in the previous 6 hours, with no symptomatic hypotension, intensification of intravenous diuretics, or use of intravenous vasodilators during that time period, and no intravenous inotropes in the previous 24 hours.

Enalapril was titrated to a target dose of 10 mg twice daily. Sacubitril/valsartan was titrated to a target dose of 97/103 mg twice daily. Titration was carried out using an algorithm based upon systolic BP. If the SBP was at least 100 and less than 120 mm Hg at baseline, sacubitril/valsartan was initiated at 24/26 mg twice daily, enalapril at 2.5 mg b.i.d. If the SBP at randomization was 120 mm Hg or higher, the initial dosing was sacubitril/valsartan at 49/51 mm Hg b.i.d. or enalapril at 5 mg b.i.d. Up-titration occurred after 1 week, then biweekly through week 8.

PIONEER in perspective

Bruce Jancin/MDedge News

Discussant Larry A. Allen, MD, a heart failure specialist at the University of Colorado at Denver, Aurora, predicted that this will be a practice-changing study.

“There has been a need for a study like PIONEER in heart failure,” he observed. While multiple randomized trials have advanced the treatment of ambulatory HFrEF patients, demonstrating benefit for initiation and intensification of treatment with ACE inhibitors, angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, the treatment of patients with ADHF has remained relatively static, marked by failed trials of once-promising novel agents including tolvaptan, nesiritide, and serelaxin.

“All the data is in ambulatory patients, but the action for the care of heart failure patients actually occurs largely in the hospital. Seventy percent of care provided in the U.S. to patients with heart failure occurs in the hospital setting. These patients are a captive audience at that time, and the transitions from inpatient to outpatient care are fragile,” Dr. Allen said.

He noted that the use of sacubitril/valsartan in routine practice as reflected in national registries has been “extremely low” – less than 15% among eligible patients – despite the drug having been approved more than 3 years ago. One major reason for the low uptake, in his view, is clinical inertia. That should melt away in what he termed “the post-PIONEER world.”

“I think one of the great things about this study is it keeps it simple. We now have a simpler algorithm for inpatient and subsequent outpatient management of heart failure with reduced ejection fraction. It’s easier for us to start with the treatment we want patients to be on, and it’s better for patients, too. Most importantly, this study reinforces the importance and safety of aggressive guideline-directed medical therapy starting from the beginning in most patients,” Dr. Allen said.

The study findings were published simultaneously in the New England Journal of Medicine (2018 Nov 11. doi: 10.1056/NEJMoa1812851).

PIONEER-HF was sponsored by Novartis. Dr. Velazquez reported receiving research grants from and serving as a consultant to that company and others. Dr. Allen reported having no financial conflicts.

[email protected]

Background: Atrial fibrillation (AF) is a well-known risk factor for ischemic stroke; however, it is unclear if atrial fibrillation burden in patients with PAF is correlated with increased stroke risk.

Patients in the highest tertile of PAF burden (less than 11%) had 215% higher risk of thromboembolic events, compared with those with lower PAF burden (less than 11%), yielding a hazard ratio of 3.15 (95% confidence interval, 1.51-6.61), even after adjustment.

This study was limited by short ECG monitoring period (14 days), low total number of events (29 total events, 17 in the highest tertile), and no minimum follow-up time. Further, with all patients insured in a single health care system, and excluded on disenrollment from the health plan, selection bias could have affected the results.

Bottom line: In patients with PAF, a larger AF burden (greater than 11%) is associated with increased risk of ischemic stroke. Assessment of AF burden may help determine the need for anticoagulation for stroke prevention.

Citation: Go AS et al. Association of burden of atrial fibrillation with risk of ischemic stroke in adults with paroxysmal atrial fibrillation: the KP-RHYTHM study. JAMA Cardiol. 2018 Jul 1;3(7):601-8.

Dr. Hanna is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Background: Atrial fibrillation (AF) is a well-known risk factor for ischemic stroke; however, it is unclear if atrial fibrillation burden in patients with PAF is correlated with increased stroke risk.

Patients in the highest tertile of PAF burden (less than 11%) had 215% higher risk of thromboembolic events, compared with those with lower PAF burden (less than 11%), yielding a hazard ratio of 3.15 (95% confidence interval, 1.51-6.61), even after adjustment.

This study was limited by short ECG monitoring period (14 days), low total number of events (29 total events, 17 in the highest tertile), and no minimum follow-up time. Further, with all patients insured in a single health care system, and excluded on disenrollment from the health plan, selection bias could have affected the results.

Bottom line: In patients with PAF, a larger AF burden (greater than 11%) is associated with increased risk of ischemic stroke. Assessment of AF burden may help determine the need for anticoagulation for stroke prevention.

Citation: Go AS et al. Association of burden of atrial fibrillation with risk of ischemic stroke in adults with paroxysmal atrial fibrillation: the KP-RHYTHM study. JAMA Cardiol. 2018 Jul 1;3(7):601-8.

Dr. Hanna is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Background: Atrial fibrillation (AF) is a well-known risk factor for ischemic stroke; however, it is unclear if atrial fibrillation burden in patients with PAF is correlated with increased stroke risk.

Patients in the highest tertile of PAF burden (less than 11%) had 215% higher risk of thromboembolic events, compared with those with lower PAF burden (less than 11%), yielding a hazard ratio of 3.15 (95% confidence interval, 1.51-6.61), even after adjustment.

This study was limited by short ECG monitoring period (14 days), low total number of events (29 total events, 17 in the highest tertile), and no minimum follow-up time. Further, with all patients insured in a single health care system, and excluded on disenrollment from the health plan, selection bias could have affected the results.

Bottom line: In patients with PAF, a larger AF burden (greater than 11%) is associated with increased risk of ischemic stroke. Assessment of AF burden may help determine the need for anticoagulation for stroke prevention.

Citation: Go AS et al. Association of burden of atrial fibrillation with risk of ischemic stroke in adults with paroxysmal atrial fibrillation: the KP-RHYTHM study. JAMA Cardiol. 2018 Jul 1;3(7):601-8.

Dr. Hanna is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

CHICAGO – Dr. Larry A. Allen will now have an easier time of treating hospitalized patients with acute decompensated heart failure because of the results of the PIONEER-HF trial.

That study examined whether in-hospital initiation of sacubitril/valsartan compared to enalapril is safe and effective in ADHF, a treatment that hasn’t been studied well or taken up in clinical practice.

In PIONEER-HF, compared with enalipril, sacubitril/valsaran reduced NT-proBNP significantly from baseline to week 8 by 29%, showed comparable safety, and reduced composite endpoint of death, rehospitalization for heart failure, implantation of a left-ventricular implant device, and need for a transplant by 46%.

Dr. Allen, of the University of Colorado, Denver, was the designated discussant for the PIONEER-HF presentation at the American Heart Association scientific sessions. In an interview, he explained how these results will change his practice as a heart failure specialist. “It simplifies things: I don’t have to start on an old therapy in the hospital, get the patients back in clinic, and switch the over to this newer therapy. I can just start from the beginning with the therapy that I think will be most effective.”

To find out why, watch the complete interview.

CHICAGO – Dr. Larry A. Allen will now have an easier time of treating hospitalized patients with acute decompensated heart failure because of the results of the PIONEER-HF trial.

That study examined whether in-hospital initiation of sacubitril/valsartan compared to enalapril is safe and effective in ADHF, a treatment that hasn’t been studied well or taken up in clinical practice.

In PIONEER-HF, compared with enalipril, sacubitril/valsaran reduced NT-proBNP significantly from baseline to week 8 by 29%, showed comparable safety, and reduced composite endpoint of death, rehospitalization for heart failure, implantation of a left-ventricular implant device, and need for a transplant by 46%.

Dr. Allen, of the University of Colorado, Denver, was the designated discussant for the PIONEER-HF presentation at the American Heart Association scientific sessions. In an interview, he explained how these results will change his practice as a heart failure specialist. “It simplifies things: I don’t have to start on an old therapy in the hospital, get the patients back in clinic, and switch the over to this newer therapy. I can just start from the beginning with the therapy that I think will be most effective.”

To find out why, watch the complete interview.

CHICAGO – Dr. Larry A. Allen will now have an easier time of treating hospitalized patients with acute decompensated heart failure because of the results of the PIONEER-HF trial.

That study examined whether in-hospital initiation of sacubitril/valsartan compared to enalapril is safe and effective in ADHF, a treatment that hasn’t been studied well or taken up in clinical practice.

In PIONEER-HF, compared with enalipril, sacubitril/valsaran reduced NT-proBNP significantly from baseline to week 8 by 29%, showed comparable safety, and reduced composite endpoint of death, rehospitalization for heart failure, implantation of a left-ventricular implant device, and need for a transplant by 46%.

Dr. Allen, of the University of Colorado, Denver, was the designated discussant for the PIONEER-HF presentation at the American Heart Association scientific sessions. In an interview, he explained how these results will change his practice as a heart failure specialist. “It simplifies things: I don’t have to start on an old therapy in the hospital, get the patients back in clinic, and switch the over to this newer therapy. I can just start from the beginning with the therapy that I think will be most effective.”

To find out why, watch the complete interview.

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Among direct oral anticoagulants, apixaban (Eliquis) has shown fewer stroke events and bleeding than warfarin in patients with atrial fibrillation, according to results of an updated comparative effectiveness review.

Dabigatran (Pradaxa), by contrast, has shown reductions in stroke events but a similar rate of bleeding events compared to warfarin, according to the report from the Duke Evidence-based Practice Center, Durham, N.C.

Rivaroxaban (Xarelto), meanwhile, is “similar in both benefits and harms with warfarin” in evidence to date, investigators wrote in the report, which was prepared for the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI).

Finally, edoxaban (Savaysa) is “most likely similar” to warfarin with respect to preventing stroke or systemic embolism, with less risk for major bleeding and hemorrhagic stroke, investigators wrote in a summary of their findings on the AHRQ website.

“Effectiveness of these direct oral anticoagulants as compared to one another however is limited by the lack of randomized studies directly comparing their safety and effectiveness,” concluded investigators, led by Gillian D. Sanders, PhD, of Duke University.

The 612-page report details a systematic review based on 320 articles representing 185 unique studies. The review was designed to update a 2013 AHRQ report that evaluated evidence not only for treatment options to prevent stroke in patients with atrial fibrillation, but also for tools used to predict risk of stroke or bleeding.

In the 2013 report, investigators concluded that the newer anticoagulants showed “early promise” in reducing stroke and bleeding events compared with warfarin.

That earlier report said that CHA₂ and CHA₂DS₂-VASc had the best evidence to support prediction of stroke events, while HAS-BLED provided the best discrimination of bleeding risk.

The updated report adds the ABC stroke risk score as a tool that, along with CHADS2 and CHA2DS2-VASc, has the “best evidence” predicting thromboembolic risk, authors said.

Imaging tools, on the other hand, still need more evidence supporting their use to predict thromboembolic risk, Dr. Sanders and colleagues said in their report.

The literature review, which covered the January 2000 through February 2018, turned up 61 studies relevant to predicting thromboembolic risk, 38 on bleeding risk, and 117 on preventing thromboembolic events with anticoagulation therapies, antiplatelet therapies, or procedures.

Direct oral anticoagulants were evaluated in randomized clinical trials that were “often very large, of good quality, and considered definitive in the field,” Dr. Sanders and colleagues wrote in their report.

However, these trials were constrained to comparing direct oral anticoagulants with warfarin or aspirin, and have not involved head-to-head comparison among the newer agents, they added.

“Based on these trials though, clinical leaders and professional societies have determined that these newer agents are better than the prior lone treatment of warfarin in terms of stroke prevention, side effects, and risk of bleeding,” they said in the published report.
 

SOURCE: Sanders GD, et al. 2018 Oct 30. AHRQ Publication No. 18(19)-EHC018-EF.
 

Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.

©Thinkstock

Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.

The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).

Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.

Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).

The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.

“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.

But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.

“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.

Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.

The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.

The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.

They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.

“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”

No conflicts of interest were declared.

SOURCE: Hersh AM et al. CHEST. 2018 Nov;154(5):1044-51.

Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.

©Thinkstock

Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.

The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).

Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.

Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).

The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.

“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.

But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.

“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.

Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.

The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.

The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.

They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.

“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”

No conflicts of interest were declared.

SOURCE: Hersh AM et al. CHEST. 2018 Nov;154(5):1044-51.

Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.

©Thinkstock

Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.

The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).

Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.

Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).

The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.

“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.

But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.

“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.

Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.

The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.

The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.

They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.

“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”

No conflicts of interest were declared.

SOURCE: Hersh AM et al. CHEST. 2018 Nov;154(5):1044-51.

Background: An increasing body of literature suggests that hyperoxia may be harmful, yet liberal use of supplemental oxygen remains widespread.

Much like transfusion thresholds, more may not always be better when it comes to supplemental oxygen. Hospitalists should consider the harmful effects of hyperoxia when caring for patients on supplemental oxygen. Unfortunately, median blood oxygen saturation during therapy was not available for each group in this trial, so more research is needed to clearly define the upper limit of oxygen saturation at which harm outweighs benefit.

Bottom line: When compared to conservative oxygen administration, liberal oxygen therapy increases mortality in acutely ill adults.

Citation: Chu DK et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-705.

Dr. Metter is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Background: An increasing body of literature suggests that hyperoxia may be harmful, yet liberal use of supplemental oxygen remains widespread.

Much like transfusion thresholds, more may not always be better when it comes to supplemental oxygen. Hospitalists should consider the harmful effects of hyperoxia when caring for patients on supplemental oxygen. Unfortunately, median blood oxygen saturation during therapy was not available for each group in this trial, so more research is needed to clearly define the upper limit of oxygen saturation at which harm outweighs benefit.

Bottom line: When compared to conservative oxygen administration, liberal oxygen therapy increases mortality in acutely ill adults.

Citation: Chu DK et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-705.

Dr. Metter is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Background: An increasing body of literature suggests that hyperoxia may be harmful, yet liberal use of supplemental oxygen remains widespread.

Much like transfusion thresholds, more may not always be better when it comes to supplemental oxygen. Hospitalists should consider the harmful effects of hyperoxia when caring for patients on supplemental oxygen. Unfortunately, median blood oxygen saturation during therapy was not available for each group in this trial, so more research is needed to clearly define the upper limit of oxygen saturation at which harm outweighs benefit.

Bottom line: When compared to conservative oxygen administration, liberal oxygen therapy increases mortality in acutely ill adults.

Citation: Chu DK et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-705.

Dr. Metter is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

The Food and Drug Administration has granted 510(k) clearance for PixCell Medical’s HemoScreen, a portable hematology analyzer is used to perform a complete blood count at the point of care.

HemoScreen requires a single drop of blood and uses disposable cartridges that provide automatic sample preparation.

HemoScreen can analyze 20 standard complete blood count parameters and produces results within 5 minutes.

Study results suggested that HemoScreen provides results comparable to those of another hematology analyzer, Sysmex XE-2100 (J Clin Pathol. 2016 Aug;69[8]:720-5).

“The HemoScreen delivers lab accurate results,” Avishay Bransky, PhD, CEO of PixCell, said in a statement.

HemoScreen “would be especially useful” in physicians’ offices, emergency rooms, intensive care units, oncology clinics, and remote locations, he added.

HemoScreen makes use of a technology called viscoelastic focusing, which employs microfluidics and machine vision algorithms to analyze cells.

[email protected]

Clinical question: Does surgical repair of hip fractures in nursing home residents with advanced dementia reduce adverse outcomes?

Background: Hip fractures are common in the advanced dementia nursing home population. The benefit of surgical repair is unclear in this population given significant baseline functional disability and limited life expectancy.

Study design: Retrospective cohort study.

Setting: Medicare claims data set.

Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Does surgical repair of hip fractures in nursing home residents with advanced dementia reduce adverse outcomes?

Background: Hip fractures are common in the advanced dementia nursing home population. The benefit of surgical repair is unclear in this population given significant baseline functional disability and limited life expectancy.

Study design: Retrospective cohort study.

Setting: Medicare claims data set.

Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Does surgical repair of hip fractures in nursing home residents with advanced dementia reduce adverse outcomes?

Background: Hip fractures are common in the advanced dementia nursing home population. The benefit of surgical repair is unclear in this population given significant baseline functional disability and limited life expectancy.

Study design: Retrospective cohort study.

Setting: Medicare claims data set.

Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.