Clinical

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

In a large prospectively collected database, the risk of death at 30 days in ICU patients was far greater in those with hospital-acquired pneumonia (HAP) than in those with ventilator-associated pneumonia (VAP) even after adjustment for prognostic factors, according to a large study that compared mortality risk for these complications.

copyright Andrei Malov/Thinkstock

The data for this newly published study were drawn from an evaluation of 14,212 patients treated at 23 ICUs participating in a collaborative French network OUTCOMEREA and published Critical Care Medicine.

HAP in ICU patients “was associated with an 82% increase in the risk of death at day 30,” reported a team of investigators led by Wafa Ibn Saied, MD, of the Université Paris Diderot. Although VAP and HAP were independent risk factors (P both less than .0001) for death at 30 days, VAP increased risk by 38%, less than half of HAP, which increased risk by 82%.

From an observational but prospective database initiated in 1997, this study evaluated 7,735 ICU patients at risk for VAP and 9,747 at risk for HAP. Of those at risk, defined by several factors including an ICU stay of more than 48 hours, HAP developed in 8% and VAP developed in 1%.

The 30-day mortality rates at 30 days after pneumonia were 23.9% for HAP and 28.4% for VAP. The greater risk of death by HR was identified after an analysis that adjusted for mortality risk factors, the adequacy of initial treatment, and other factors, such as prior history of pneumonia.

In HAP patients, the rate of mortality at 30 days was 32% in the 75 who were reintubated but only 16% in the 101 who were not. Adequate empirical therapy within the first 24 hours for HAP was not associated with a reduction in the risk of death.

As in the HAP patients, mortality was not significantly higher in VAP patients who received inadequate empirical therapy, compared with those who did, according to the authors.

Previous studies have suggested that both HAP and VAP increase risk of death in ICU patients, but the authors of this study believe that the relative risk of HAP “is underappreciated.” They asserted, based on these most recent data as well as on previously published analyses, that nonventilated HAP results in “significant increases in cost, length of stay, and mortality.”

The researchers had no disclosures.

SOURCE: Saied WI et al. Crit Care Med. 2018 Nov 7. doi: 10.1097/CCM.0000000000003553.

In a large prospectively collected database, the risk of death at 30 days in ICU patients was far greater in those with hospital-acquired pneumonia (HAP) than in those with ventilator-associated pneumonia (VAP) even after adjustment for prognostic factors, according to a large study that compared mortality risk for these complications.

copyright Andrei Malov/Thinkstock

The data for this newly published study were drawn from an evaluation of 14,212 patients treated at 23 ICUs participating in a collaborative French network OUTCOMEREA and published Critical Care Medicine.

HAP in ICU patients “was associated with an 82% increase in the risk of death at day 30,” reported a team of investigators led by Wafa Ibn Saied, MD, of the Université Paris Diderot. Although VAP and HAP were independent risk factors (P both less than .0001) for death at 30 days, VAP increased risk by 38%, less than half of HAP, which increased risk by 82%.

From an observational but prospective database initiated in 1997, this study evaluated 7,735 ICU patients at risk for VAP and 9,747 at risk for HAP. Of those at risk, defined by several factors including an ICU stay of more than 48 hours, HAP developed in 8% and VAP developed in 1%.

The 30-day mortality rates at 30 days after pneumonia were 23.9% for HAP and 28.4% for VAP. The greater risk of death by HR was identified after an analysis that adjusted for mortality risk factors, the adequacy of initial treatment, and other factors, such as prior history of pneumonia.

In HAP patients, the rate of mortality at 30 days was 32% in the 75 who were reintubated but only 16% in the 101 who were not. Adequate empirical therapy within the first 24 hours for HAP was not associated with a reduction in the risk of death.

As in the HAP patients, mortality was not significantly higher in VAP patients who received inadequate empirical therapy, compared with those who did, according to the authors.

Previous studies have suggested that both HAP and VAP increase risk of death in ICU patients, but the authors of this study believe that the relative risk of HAP “is underappreciated.” They asserted, based on these most recent data as well as on previously published analyses, that nonventilated HAP results in “significant increases in cost, length of stay, and mortality.”

The researchers had no disclosures.

SOURCE: Saied WI et al. Crit Care Med. 2018 Nov 7. doi: 10.1097/CCM.0000000000003553.

In a large prospectively collected database, the risk of death at 30 days in ICU patients was far greater in those with hospital-acquired pneumonia (HAP) than in those with ventilator-associated pneumonia (VAP) even after adjustment for prognostic factors, according to a large study that compared mortality risk for these complications.

copyright Andrei Malov/Thinkstock

The data for this newly published study were drawn from an evaluation of 14,212 patients treated at 23 ICUs participating in a collaborative French network OUTCOMEREA and published Critical Care Medicine.

HAP in ICU patients “was associated with an 82% increase in the risk of death at day 30,” reported a team of investigators led by Wafa Ibn Saied, MD, of the Université Paris Diderot. Although VAP and HAP were independent risk factors (P both less than .0001) for death at 30 days, VAP increased risk by 38%, less than half of HAP, which increased risk by 82%.

From an observational but prospective database initiated in 1997, this study evaluated 7,735 ICU patients at risk for VAP and 9,747 at risk for HAP. Of those at risk, defined by several factors including an ICU stay of more than 48 hours, HAP developed in 8% and VAP developed in 1%.

The 30-day mortality rates at 30 days after pneumonia were 23.9% for HAP and 28.4% for VAP. The greater risk of death by HR was identified after an analysis that adjusted for mortality risk factors, the adequacy of initial treatment, and other factors, such as prior history of pneumonia.

In HAP patients, the rate of mortality at 30 days was 32% in the 75 who were reintubated but only 16% in the 101 who were not. Adequate empirical therapy within the first 24 hours for HAP was not associated with a reduction in the risk of death.

As in the HAP patients, mortality was not significantly higher in VAP patients who received inadequate empirical therapy, compared with those who did, according to the authors.

Previous studies have suggested that both HAP and VAP increase risk of death in ICU patients, but the authors of this study believe that the relative risk of HAP “is underappreciated.” They asserted, based on these most recent data as well as on previously published analyses, that nonventilated HAP results in “significant increases in cost, length of stay, and mortality.”

The researchers had no disclosures.

SOURCE: Saied WI et al. Crit Care Med. 2018 Nov 7. doi: 10.1097/CCM.0000000000003553.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

San Diego – In patients with atrial fibrillation who had direct oral anticoagulant (DOAC) interruption for an elective surgery, a simple and standardized management strategy yielded low rates of bleeding and thromboembolism, according to results of a prospective study of more than 3,000 patients.

Rates of major bleeding were less than 2% and rates of arterial thromboembolism were less than 1% in patients managed in accordance with the strategy, which foregoes heparin bridging and preoperative coagulation testing, according to investigator James D. Douketis, MD, of St. Joseph’s Healthcare and McMaster University, Hamilton, Ont.

“This is the first study to demonstrate the safety of a standardized perioperative management approach in a patients with atrial fibrillation who are taking a DOAC, and we hope will establish a standard and will have an effect on our clinical practice guidelines,” Dr. Douketis said during a press briefing at the annual meeting of the American Society of Hematology.

This trial offers the “most definitive evidence to date” that atrial fibrillation patients can – in an organized fashion based on bleeding risk – safely stop taking DOACs, said Mark Crowther, MD, chair and professor of medicine at McMaster University.

“This study will almost instantaneously establish a treatment practice and a treatment standard for the vast number of patients in North America and around the world who take these drugs,” added Dr. Crowther, who moderated the press briefing.

The PAUSE study included three parallel cohorts of atrial fibrillation patients taking DOACs (apixaban, dabigatran, or rivaroxaban) who required anticoagulant interruption for an elective surgery or procedure.

The DOAC interruptions were done using standardized protocols based on the pharmacokinetic properties of each DOAC, procedure-associated bleeding risk, and creatinine clearance, the investigators reported.

The interruptions occurred 1 day before and after low bleeding risk surgeries, and 2 days before and after high bleeding risk surgeries, while longer interruptions were used in patients receiving dabigatran who had a creatinine clearance below 50 mL/min.

A total of 3,007 patients at 23 sites in Canada, the United States, and Europe were managed by this approach in the PAUSE study – 1,257 patients receiving apixaban, 668 receiving dabigatran, and 1,082 receiving rivaroxaban – and were evaluated weekly for 30 days post-procedure.

PAUSE is the largest study to date that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care.

The 30-day postoperative rate of major bleeding was low, according to investigators, at 1.35% (95% confidence interval, 0-2.00%) for apixaban, 0.90% (95% CI, 0-1.73%) for dabigatran, and 1.85% (95% CI, 0-2.65%) for rivaroxaban, Dr. Douketis reported.

Likewise, the rate of arterial thromboembolism was low at 0.16% (95% CI, 0-0.48%) for apixaban, 0.6% (95% CI, 0-1.33%) for dabigatran, and 0.37% (95% CI, 0-0.82%) for rivaroxaban, he said.

Most patients (greater than 90%) had minimal to no residual DOAC levels at the time of surgery, the investigator added.

The study was funded by the Canadian Institutes of Health Research and the H&S Foundation of Canada. Dr. Douketis reported disclosures related to Janssen, which makes rivaroxaban; Boehringer-Ingelheim, which makes dabigatran; and other companies. Dr. Crowther reported financial relationships with Bristol-Myers Squibb and other companies.

SOURCE: Douketis J et al. ASH 2018, Abstract LBA-5.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.

EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.

“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.

The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.

The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.

On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.

Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.

Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).

Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.

Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.

The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.

In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.

Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.

“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.

Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.

Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.

SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

CHICAGO – Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.

The findings come from an analysis of insurance claims data from more than 50,000 U.S. patients – the largest observational study to date to compare these three direct-acting oral anticoagulants (DOACs) in octogenarians with nonvalvular atrial fibrillation, Steven B. Deitelzweig, MD, said at the American Heart Association scientific sessions.

“The results may help clinicians evaluate the risk-benefit ratio of the DOACs” in this population, said Dr. Deitelzweig, vice president for medical affairs at Ochsner Medical Center in New Orleans.

He noted that the results were consistent with prior reports from observational data and registries, as well as the results in a recent analysis commissioned by the Agency for Healthcare Research and Quality. “We see a consistent message that apixaban always has less risk for major bleeding, and at least comparable efficacy” when compared with other DOACs, he said in a video interview.

And for the foreseeable future, this sort of data will need to suffice for clinicians trying to decide which DOAC to use because “I know of no head-to-head trials, nor do I anticipate any head-to-head trials” that could provide a more definitive comparison of the DOACs, Dr. Deitelzweig said.

The data came from a large number of patients – about 38% of the U.S. population – which boosts the generalizability of the finding. “I think our data are useful” for helping to make treatment decisions, he concluded.

The analysis he reported came from the ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) study, which pooled U.S. insurance claims data from several sources. For the octogenarian study, Dr. Deitelzweig and his associates used data from about 123 million U.S. residents collected between January 2012 and September 2015 by Medicare and three different commercial insurance databases. The overall level of beneficiary overlap between these four data sources was less than 0.5%.

The researchers identified patients with nonvalvular atrial fibrillation who started anticoagulant treatment with a DOAC and were at least 80 years old. This included 19,752 patients started on apixaban (Eliquis), 6,741 started on dabigatran (Pradaxa), and 27,217 started on rivaroxaban (Xarelto). A majority of the patients were at least 84 years old.

The analysis used propensity-score matching to compare similar patients and to minimize the impact of potentially confounding differences among the patients in each treatment subgroup. During a median follow-up of 7-9 months, the incidence of stroke or systemic embolism was 35% lower in the apixaban-treated patients, compared with those who received dabigatran, and 28% lower in the apixaban patients, compared with those treated with rivaroxaban, both statistically significant differences, Dr. Deitelzweig reported. The incidence of major bleeding episodes was 40% lower with apixaban than with dabigatran and 50% lower with apixaban, compared with rivaroxaban, also statistically significant differences.

When the analysis compared dabigatran with rivaroxaban it showed no statistically significant difference for the efficacy endpoint, but dabigatran produced 23% fewer major bleeds than rivaroxaban, a statistically significant difference.

These findings jibed with a recently published analysis from Dr. Deitelzweig and his associates that used data from all adults with nonvalvular atrial fibrillation started on an oral anticoagulant in an expanded ARISTOPHANES database for 2012-2015 that included more than 180 million U.S. beneficiaries. After propensity-score matching, this created subgroups of about 58,000 patients started on apixaban, nearly 27,000 started on dabigatran, and more than 83,000 started on rivaroxaban. The patients averaged about 73 years old. Again, with about 7-9 months of follow-up, very similar outcomes occurred. Patients on apixaban had significantly fewer strokes and systemic embolic events as well as significantly fewer major bleeds compared with patients treated with one of the other DOACs (Stroke. 2018 Dec;49[12]:2933-44).

The study was funded by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Deitelzweig is a consultant to and speaker on behalf of Bristol-Myers Squibb and Pfizer. He is also a consultant to or speaker on behalf of Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Portola Pharmaceuticals.

[email protected]

SOURCE: Deitelzweig SB et al. Circulation. 2018 Nov 6;138(suppl 1):A14900.

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

The American Society of Hematology has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism.

The new guidelines, released on Nov. 27, contain more than 150 individual recommendations, including sections devoted to managing venous thromboembolism (VTE) during pregnancy and in pediatric patients. Guideline highlights cited by some of the writing-panel participants included a high reliance on low-molecular-weight heparin (LMWH) agents as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

The guidelines took more than 3 years to develop, an effort that began in 2015.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, cochair of the guideline-writing group and a hematologist and thrombosis specialist at the University of Pennsylvania, Philadelphia, said during a webcast to unveil the new guidelines.

Prevention

For preventing VTE in hospitalized medical patients the guidelines recommended initial assessment of the patient’s risk for both VTE and bleeding. Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves. But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, professor and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, said Dr. Cushman, a member of the writing group. The panel also endorsed LMWH over a direct-acting oral anticoagulant, both during hospitalization and following discharge. The guidelines for prevention in medical patients explicitly “recommended against” using a direct-acting oral anticoagulant “over other treatments” both for hospitalized medical patients and after discharge, and the guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important takeaway from the prevention section was a statement that combining both mechanical and medical prophylaxis was not needed for medical inpatients. And once patients are discharged, if they take a long air trip they have no need for compression stockings or aspirin if their risk for thrombosis is not elevated. People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommended the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, noted Dr. Lim, a hematologist and professor at McMaster University, Hamilton, Ont.

The guidelines also recommended using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy. But it’s a level of care that many U.S. patients don’t currently receive and hence is an area ripe for growth, said Daniel M. Witt, PharmD, professor and vice-chair of pharmacotherapy at the University of Utah, Salt Lake City.

CDC/Janice Carr

The guidelines recommended against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure. The guidelines also called for “thoughtful” use of anticoagulant reversal agents and advised that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, said Dr. Cuker (Blood. 2012 Nov 15;120[20]:4160-7). The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated with heparin annually: argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis in medical patients, diagnosis, therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children. The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said that these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published six articles in the journal Blood Advances that detailed the guidelines and their documentation.

The articles include prophylaxis of medical patients (Blood Advances. 2018 Nov 27;2[22]:3198-225), diagnosis (Blood Advances. 2018 Nov 27;2[22]:3226-56), anticoagulation therapy (Blood Advances. 2018 Nov 27;2[22]:3257-91), pediatrics (Blood Advances. 2018 Nov 27;2[22]:3292-316), pregnancy (Blood Advances. 2018 Nov 27;2[22]:3317-59), and heparin-induced thrombocytopenia (Blood Advances. 2018 Nov 27;2[22]:3360-92).

Dr. Cushman, Dr. Lim, and Dr. Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.

[email protected]

The American Society of Hematology has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism.

The new guidelines, released on Nov. 27, contain more than 150 individual recommendations, including sections devoted to managing venous thromboembolism (VTE) during pregnancy and in pediatric patients. Guideline highlights cited by some of the writing-panel participants included a high reliance on low-molecular-weight heparin (LMWH) agents as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

The guidelines took more than 3 years to develop, an effort that began in 2015.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, cochair of the guideline-writing group and a hematologist and thrombosis specialist at the University of Pennsylvania, Philadelphia, said during a webcast to unveil the new guidelines.

Prevention

For preventing VTE in hospitalized medical patients the guidelines recommended initial assessment of the patient’s risk for both VTE and bleeding. Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves. But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, professor and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, said Dr. Cushman, a member of the writing group. The panel also endorsed LMWH over a direct-acting oral anticoagulant, both during hospitalization and following discharge. The guidelines for prevention in medical patients explicitly “recommended against” using a direct-acting oral anticoagulant “over other treatments” both for hospitalized medical patients and after discharge, and the guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important takeaway from the prevention section was a statement that combining both mechanical and medical prophylaxis was not needed for medical inpatients. And once patients are discharged, if they take a long air trip they have no need for compression stockings or aspirin if their risk for thrombosis is not elevated. People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommended the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, noted Dr. Lim, a hematologist and professor at McMaster University, Hamilton, Ont.

The guidelines also recommended using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy. But it’s a level of care that many U.S. patients don’t currently receive and hence is an area ripe for growth, said Daniel M. Witt, PharmD, professor and vice-chair of pharmacotherapy at the University of Utah, Salt Lake City.

CDC/Janice Carr

The guidelines recommended against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure. The guidelines also called for “thoughtful” use of anticoagulant reversal agents and advised that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, said Dr. Cuker (Blood. 2012 Nov 15;120[20]:4160-7). The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated with heparin annually: argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis in medical patients, diagnosis, therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children. The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said that these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published six articles in the journal Blood Advances that detailed the guidelines and their documentation.

The articles include prophylaxis of medical patients (Blood Advances. 2018 Nov 27;2[22]:3198-225), diagnosis (Blood Advances. 2018 Nov 27;2[22]:3226-56), anticoagulation therapy (Blood Advances. 2018 Nov 27;2[22]:3257-91), pediatrics (Blood Advances. 2018 Nov 27;2[22]:3292-316), pregnancy (Blood Advances. 2018 Nov 27;2[22]:3317-59), and heparin-induced thrombocytopenia (Blood Advances. 2018 Nov 27;2[22]:3360-92).

Dr. Cushman, Dr. Lim, and Dr. Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.

[email protected]

The American Society of Hematology has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism.

The new guidelines, released on Nov. 27, contain more than 150 individual recommendations, including sections devoted to managing venous thromboembolism (VTE) during pregnancy and in pediatric patients. Guideline highlights cited by some of the writing-panel participants included a high reliance on low-molecular-weight heparin (LMWH) agents as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.

The guidelines took more than 3 years to develop, an effort that began in 2015.

An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, cochair of the guideline-writing group and a hematologist and thrombosis specialist at the University of Pennsylvania, Philadelphia, said during a webcast to unveil the new guidelines.

Prevention

For preventing VTE in hospitalized medical patients the guidelines recommended initial assessment of the patient’s risk for both VTE and bleeding. Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves. But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, professor and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, said Dr. Cushman, a member of the writing group. The panel also endorsed LMWH over a direct-acting oral anticoagulant, both during hospitalization and following discharge. The guidelines for prevention in medical patients explicitly “recommended against” using a direct-acting oral anticoagulant “over other treatments” both for hospitalized medical patients and after discharge, and the guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.

Another important takeaway from the prevention section was a statement that combining both mechanical and medical prophylaxis was not needed for medical inpatients. And once patients are discharged, if they take a long air trip they have no need for compression stockings or aspirin if their risk for thrombosis is not elevated. People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.

Diagnosis

For diagnosis, Wendy Lim, MD, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and helps avoid unnecessary testing.

For patients with low pretest probability, the guidelines recommended the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, noted Dr. Lim, a hematologist and professor at McMaster University, Hamilton, Ont.

The guidelines also recommended using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.

Management

Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy. But it’s a level of care that many U.S. patients don’t currently receive and hence is an area ripe for growth, said Daniel M. Witt, PharmD, professor and vice-chair of pharmacotherapy at the University of Utah, Salt Lake City.

CDC/Janice Carr

The guidelines recommended against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure. The guidelines also called for “thoughtful” use of anticoagulant reversal agents and advised that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.

For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, said Dr. Cuker (Blood. 2012 Nov 15;120[20]:4160-7). The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated with heparin annually: argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.

ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis in medical patients, diagnosis, therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children. The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said that these additional documents will post sometime in 2019.

At the time of the release, the guidelines panel published six articles in the journal Blood Advances that detailed the guidelines and their documentation.

The articles include prophylaxis of medical patients (Blood Advances. 2018 Nov 27;2[22]:3198-225), diagnosis (Blood Advances. 2018 Nov 27;2[22]:3226-56), anticoagulation therapy (Blood Advances. 2018 Nov 27;2[22]:3257-91), pediatrics (Blood Advances. 2018 Nov 27;2[22]:3292-316), pregnancy (Blood Advances. 2018 Nov 27;2[22]:3317-59), and heparin-induced thrombocytopenia (Blood Advances. 2018 Nov 27;2[22]:3360-92).

Dr. Cushman, Dr. Lim, and Dr. Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.

[email protected]

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Opioids are still often overprescribed after surgery and the quantity of the prescription is associated with higher patient-reported consumption, according to a population-based study of surgery patients.

sdominick/iStock/Getty Images

Ryan Howard, MD, FACS, of the department of surgery at the University of Michigan, Ann Arbor, and his coauthors analyzed data from the Michigan Surgical Quality Collaborative and sampled 2,392 patients who underwent 1 of 12 common surgical procedures in Michigan between Jan. 1 and Sept. 30, 2017, and were prescribed opioids for pain. For all patients, the quantity of opioid prescribed – converted to oral morphine equivalents (OMEs) to adjust for varying potency – was considerably greater than the quantity actually consumed by the patient, wrote Dr. Howard and his colleagues in JAMA Surgery.

The study findings have troubling implications, the authors suggested. “Overprescribing was universally observed in this cohort, affecting each of the 12 procedures analyzed. This phenomenon was not limited to single, outlier institutions, but was widespread across many hospitals. This resulted in increased opioid consumption among patients who received larger prescriptions, as well as tens of thousands of leftover pills in 9 months that entered communities across the state of Michigan.”

The median amount prescribed was 150 OMEs, the equivalent of 30 pills of hydrocodone/acetaminophen, 5/325 mg. The median consumed, as reported by patients, was 45 OMEs, or 9 pills, meaning only 27% of the prescribed amount was used. Prescription size was also strongly associated with higher consumption; patients used an additional 0.53 OMEs (95% confidence interval, 0.40-0.65; P less than .001), or 5.3 more pills, for every 10 extra pills prescribed. The larger the initial prescription, the more patients used, an association that persisted when the data were adjusted for procedure and patient-specific factors such as postoperative pain.

The study’s acknowledged limitations included an inability to estimate how many patients were contacted for patient-reported outcome collection, which obscures how representative this sample may be of the patient population in general. There was also no data gathered regarding preoperative opioid use, a near certainty in this cohort given a 3%-4% prevalence of chronic opioid use.

That said, the investigators noted that “intentionally keeping future recommendations liberal in quantity may ultimately aid with widespread adoption, especially for clinicians concerned that prescribing reductions may lead to increased pain and calls for refills after surgery.” They commended local efforts already underway to combat this issue– including their own work at the University of Michigan, where evidence-based prescribing recommendations resulted in a 63% reduction in opioid prescription size without an increase in refills or pain – but reiterated that more needs to be done at a state level.

The authors offered a possible reason for the link between prescription size and patient consumption. “A plausible explanation for the association between prescription size and medication use is the anchoring and adjustment heuristic. This is a psychologic heuristic wherein a piece of information serves as an anchor on which adjustments are made to reach an estimation or decision. For example, obesity literature has shown that food intake increases with portion size. In this case, a larger amount of opioids may serve as a mental anchor by which patients estimate their analgesic needs.”

Michael Englesbe, MD, Jennifer Waljee,MD, and Chad Brummett, MD, reported receiving funding from the Michigan Department of Health and Human Services and the National Institute on Drug Abuse. Joceline Vu, MD, reported receiving funding from the National Institutes of Health Ruth L. Kirschstein National Research Service Award; Jay Lee, MD, reported receiving funding from the National Cancer Institute.

SOURCE: Howard R et al. JAMA Surg. 2018 Nov 7. doi: 10.1001/jamasurg.2018.4234.

Clinical question

In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?

Background

Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.

In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.

Study design

Single-center quality improvement (QI) project.

Setting

Urban, 527-bed, quaternary care, free-standing children’s hospital.

Synopsis

Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.

Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.

Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.

Bottom line

Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.

Citation

Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.

Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.

Clinical question

In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?

Background

Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.

In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.

Study design

Single-center quality improvement (QI) project.

Setting

Urban, 527-bed, quaternary care, free-standing children’s hospital.

Synopsis

Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.

Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.

Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.

Bottom line

Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.

Citation

Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.

Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.

Clinical question

In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?

Background

Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.

In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.

Study design

Single-center quality improvement (QI) project.

Setting

Urban, 527-bed, quaternary care, free-standing children’s hospital.

Synopsis

Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.

Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.

Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.

Bottom line

Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.

Citation

Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.

Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.