Delayed delivery blamed for brain injury: $9.6M

At 5:00 AM, the ObGyn called for emergency cesarean delivery, requesting assistance from a surgeon and surgical scrub technician. The baby was delivered at 5:28 AM with a nuchal cord. She was limp, blue, and not breathing, with Apgar scores of 0, 2, and 3, at 1, 5, and 10 minutes, respectively. After full resuscitation, the baby was transferred to another hospital where she was treated for hypoxic-ischemic encephalopathy with therapeutic hypothermia; a feeding tube was placed.

At trial, the 3.5-year-old child is totally blind, has cerebral palsy, a seizure disorder, speech and language impairments, and continues to require frequent suctioning. She will require 24-hour licensed nursing care for life.

PARENTS’ CLAIM:

Standard of care required delivery before 4:00 AM due to fetal distress. The ObGyn was negligent in delaying cesarean delivery.

DEFENDANTS’ DEFENSE:

The ObGyn observed that labor was progressing, indicating that vaginal delivery was appropriate. A cesarean delivery was not required earlier because FHR variability persisted, showing that the fetus was not acidotic. Delivery occurred less than 30 minutes after cesarean delivery was ordered, consistent with guidelines. The infant’s injury was caused by an unpredictable cord accident and had nothing to do with an alleged delivery delay.

VERDICT:

The case was filed as a Federal Tort Claims Act case because the ObGyn was employed by a federal clinic. A California judge awarded $9,609,305 after concluding that the cesarean delivery should have occurred earlier. The hospital settled for a confidential amount.

Mother dies of PPH: $9.2 million

A woman gave birth by cesarean delivery. Shortly after surgery ended at 10:55 PM, the mother started hemorrhaging. Uterotonics and blood products were ordered. The patient was hypotensive, tachycardic, hypovolemic, and possibly still bleeding. She was transferred from the operating room (OR) to the intensive care unit (ICU) at 12:35 AM. Her ObGyn left the hospital at 12:52 AM. At 3:13 AM, a Code Blue was called and the patient was placed on a mechanical ventilator. She died 5 days later after her family elected to remove life support.

ESTATE’S CLAIM:

The ObGyn’s postoperative care of the patient was negligent. After surgery, he was absent from the OR and did not follow up with the patient after he left the hospital. The ICU nurses’ notes indicated that the patient was still actively bleeding when she entered the ICU. Despite repeated calls to the critical care specialist, the patient was left untreated by any physician until Code Blue was called.

PHYSICIANS’ DEFENSE:

After the hospital reached a pretrial confidential settlement, the suit continued against the ObGyn and critical care specialist.

The ObGyn reported that he remained in the OR and left only after placing an intrauterine balloon and administering medications that successfully controlled the PPH. He disputed the accuracy of the ICU nurses’ notes that related that the patient’s vital signs indicating active bleeding “at all times.”

The critical care specialist contended that he had recommended that the patient be kept in the OR instead of transferring her to ICU. He denied hearing from the ICU staff after 12:35 AM.

VERDICT:

A $9,284,464 California verdict was returned against the ObGyn. The jury found the critical care specialist not guilty.

Delayed delivery blamed for brain injury: $9.6M

At 5:00 AM, the ObGyn called for emergency cesarean delivery, requesting assistance from a surgeon and surgical scrub technician. The baby was delivered at 5:28 AM with a nuchal cord. She was limp, blue, and not breathing, with Apgar scores of 0, 2, and 3, at 1, 5, and 10 minutes, respectively. After full resuscitation, the baby was transferred to another hospital where she was treated for hypoxic-ischemic encephalopathy with therapeutic hypothermia; a feeding tube was placed.

At trial, the 3.5-year-old child is totally blind, has cerebral palsy, a seizure disorder, speech and language impairments, and continues to require frequent suctioning. She will require 24-hour licensed nursing care for life.

PARENTS’ CLAIM:

Standard of care required delivery before 4:00 AM due to fetal distress. The ObGyn was negligent in delaying cesarean delivery.

DEFENDANTS’ DEFENSE:

The ObGyn observed that labor was progressing, indicating that vaginal delivery was appropriate. A cesarean delivery was not required earlier because FHR variability persisted, showing that the fetus was not acidotic. Delivery occurred less than 30 minutes after cesarean delivery was ordered, consistent with guidelines. The infant’s injury was caused by an unpredictable cord accident and had nothing to do with an alleged delivery delay.

VERDICT:

The case was filed as a Federal Tort Claims Act case because the ObGyn was employed by a federal clinic. A California judge awarded $9,609,305 after concluding that the cesarean delivery should have occurred earlier. The hospital settled for a confidential amount.

Mother dies of PPH: $9.2 million

A woman gave birth by cesarean delivery. Shortly after surgery ended at 10:55 PM, the mother started hemorrhaging. Uterotonics and blood products were ordered. The patient was hypotensive, tachycardic, hypovolemic, and possibly still bleeding. She was transferred from the operating room (OR) to the intensive care unit (ICU) at 12:35 AM. Her ObGyn left the hospital at 12:52 AM. At 3:13 AM, a Code Blue was called and the patient was placed on a mechanical ventilator. She died 5 days later after her family elected to remove life support.

ESTATE’S CLAIM:

The ObGyn’s postoperative care of the patient was negligent. After surgery, he was absent from the OR and did not follow up with the patient after he left the hospital. The ICU nurses’ notes indicated that the patient was still actively bleeding when she entered the ICU. Despite repeated calls to the critical care specialist, the patient was left untreated by any physician until Code Blue was called.

PHYSICIANS’ DEFENSE:

After the hospital reached a pretrial confidential settlement, the suit continued against the ObGyn and critical care specialist.

The ObGyn reported that he remained in the OR and left only after placing an intrauterine balloon and administering medications that successfully controlled the PPH. He disputed the accuracy of the ICU nurses’ notes that related that the patient’s vital signs indicating active bleeding “at all times.”

The critical care specialist contended that he had recommended that the patient be kept in the OR instead of transferring her to ICU. He denied hearing from the ICU staff after 12:35 AM.

VERDICT:

A $9,284,464 California verdict was returned against the ObGyn. The jury found the critical care specialist not guilty.

Delayed delivery blamed for brain injury: $9.6M

At 5:00 AM, the ObGyn called for emergency cesarean delivery, requesting assistance from a surgeon and surgical scrub technician. The baby was delivered at 5:28 AM with a nuchal cord. She was limp, blue, and not breathing, with Apgar scores of 0, 2, and 3, at 1, 5, and 10 minutes, respectively. After full resuscitation, the baby was transferred to another hospital where she was treated for hypoxic-ischemic encephalopathy with therapeutic hypothermia; a feeding tube was placed.

At trial, the 3.5-year-old child is totally blind, has cerebral palsy, a seizure disorder, speech and language impairments, and continues to require frequent suctioning. She will require 24-hour licensed nursing care for life.

PARENTS’ CLAIM:

Standard of care required delivery before 4:00 AM due to fetal distress. The ObGyn was negligent in delaying cesarean delivery.

DEFENDANTS’ DEFENSE:

The ObGyn observed that labor was progressing, indicating that vaginal delivery was appropriate. A cesarean delivery was not required earlier because FHR variability persisted, showing that the fetus was not acidotic. Delivery occurred less than 30 minutes after cesarean delivery was ordered, consistent with guidelines. The infant’s injury was caused by an unpredictable cord accident and had nothing to do with an alleged delivery delay.

VERDICT:

The case was filed as a Federal Tort Claims Act case because the ObGyn was employed by a federal clinic. A California judge awarded $9,609,305 after concluding that the cesarean delivery should have occurred earlier. The hospital settled for a confidential amount.

Mother dies of PPH: $9.2 million

A woman gave birth by cesarean delivery. Shortly after surgery ended at 10:55 PM, the mother started hemorrhaging. Uterotonics and blood products were ordered. The patient was hypotensive, tachycardic, hypovolemic, and possibly still bleeding. She was transferred from the operating room (OR) to the intensive care unit (ICU) at 12:35 AM. Her ObGyn left the hospital at 12:52 AM. At 3:13 AM, a Code Blue was called and the patient was placed on a mechanical ventilator. She died 5 days later after her family elected to remove life support.

ESTATE’S CLAIM:

The ObGyn’s postoperative care of the patient was negligent. After surgery, he was absent from the OR and did not follow up with the patient after he left the hospital. The ICU nurses’ notes indicated that the patient was still actively bleeding when she entered the ICU. Despite repeated calls to the critical care specialist, the patient was left untreated by any physician until Code Blue was called.

PHYSICIANS’ DEFENSE:

After the hospital reached a pretrial confidential settlement, the suit continued against the ObGyn and critical care specialist.

The ObGyn reported that he remained in the OR and left only after placing an intrauterine balloon and administering medications that successfully controlled the PPH. He disputed the accuracy of the ICU nurses’ notes that related that the patient’s vital signs indicating active bleeding “at all times.”

The critical care specialist contended that he had recommended that the patient be kept in the OR instead of transferring her to ICU. He denied hearing from the ICU staff after 12:35 AM.

VERDICT:

A $9,284,464 California verdict was returned against the ObGyn. The jury found the critical care specialist not guilty.

The interactive video case module “Appropriate Use of Targeted Oral Anticoagulants to Prevent Stroke in Patients with Nonvalvular Atrial Fibrillation” evaluates the current guidelines and scientific evidence regarding oral anticoagulation for stroke prevention in patients with NVAF. The activity includes thorough discussions on initial management of patients with NVAF, appropriate situations for oral anticoagulation in the presence of NVAF, appropriate choice of oral anticoagulant, reversal of oral anticoagulation, as well as guidelines for oral anticoagulation and stroke prevention in NVAF patients and in special-population NVAF patients.

This free module offers up to 1.0 AMA PRA Category 1 Credit and can be found at www.shmlearningportal.org under “SHM Consults.”

The interactive video case module “Appropriate Use of Targeted Oral Anticoagulants to Prevent Stroke in Patients with Nonvalvular Atrial Fibrillation” evaluates the current guidelines and scientific evidence regarding oral anticoagulation for stroke prevention in patients with NVAF. The activity includes thorough discussions on initial management of patients with NVAF, appropriate situations for oral anticoagulation in the presence of NVAF, appropriate choice of oral anticoagulant, reversal of oral anticoagulation, as well as guidelines for oral anticoagulation and stroke prevention in NVAF patients and in special-population NVAF patients.

This free module offers up to 1.0 AMA PRA Category 1 Credit and can be found at www.shmlearningportal.org under “SHM Consults.”

The interactive video case module “Appropriate Use of Targeted Oral Anticoagulants to Prevent Stroke in Patients with Nonvalvular Atrial Fibrillation” evaluates the current guidelines and scientific evidence regarding oral anticoagulation for stroke prevention in patients with NVAF. The activity includes thorough discussions on initial management of patients with NVAF, appropriate situations for oral anticoagulation in the presence of NVAF, appropriate choice of oral anticoagulant, reversal of oral anticoagulation, as well as guidelines for oral anticoagulation and stroke prevention in NVAF patients and in special-population NVAF patients.

This free module offers up to 1.0 AMA PRA Category 1 Credit and can be found at www.shmlearningportal.org under “SHM Consults.”

Over the past two months, data from hospitalists have been collected through a survey with AmericanEHR. This feedback was incorporated into a white paper written by SHM’s IT Committee, “Hospitalists’ Attitudes Toward EHR Systems,” which will be released in October. Visit www.hospitalmedicine.org/ITEHR for updates.

Over the past two months, data from hospitalists have been collected through a survey with AmericanEHR. This feedback was incorporated into a white paper written by SHM’s IT Committee, “Hospitalists’ Attitudes Toward EHR Systems,” which will be released in October. Visit www.hospitalmedicine.org/ITEHR for updates.

Over the past two months, data from hospitalists have been collected through a survey with AmericanEHR. This feedback was incorporated into a white paper written by SHM’s IT Committee, “Hospitalists’ Attitudes Toward EHR Systems,” which will be released in October. Visit www.hospitalmedicine.org/ITEHR for updates.

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

Apixaban tablets

Photo courtesy of Pfizer

and Bristol-Myers Squibb

ROME—Novel oral anticoagulants (NOACs) are as effective as warfarin for preventing stroke but may cause less intracranial hemorrhage (ICH) in patients with atrial fibrillation, according to research presented at ESC Congress 2016.

For this study, investigators compared 3 NOACs—dabigatran, rivaroxaban, and apixaban—to warfarin in a “real-world” setting.

They found that patients had a similar risk of stroke regardless of which drug they received.

However, the risk of ICH was lower with dabigatran and apixaban than with warfarin. There was no significant difference in ICH risk between warfarin and rivaroxaban.

Laila Staerk, PhD, of Gentofte Hospital Copenhagen University Hospital in Hellerup, Denmark, presented these results at the congress as abstract 1875.* The study was supported by Velux Foundations.

“There has been a need to investigate safety and effectiveness of NOACs versus warfarin in a ‘real-world’ population, and our Danish registries provide this opportunity,” Dr Staerk said.

The study included 43,299 atrial fibrillation patients from Danish nationwide administrative registries. Roughly 42% of the patients were taking warfarin, 29% were taking dabigatran, 16% were taking apixaban, and 13% were taking rivaroxaban.

“The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials,” Dr Staerk said.

During follow-up, stroke occurred in 1054 patients, and there were 261 intracranial bleeds.

The risk of having a stroke within 1 year was similar between the treatment groups. The absolute standardized risk was 2.01% for warfarin, 2.06% for rivaroxaban, 2.12% for dabigatran, and 2.46% for apixaban.

At 1 year, the standardized absolute risk of ICH was significantly lower in patients treated with dabigatran or apixaban—0.26% and 0.40%, respectively—than in those treated with warfarin—0.60% (P<0.05). The standardized absolute risk of ICH was 0.47% with rivaroxaban, which was not significantly different than the risk with warfarin.

“The results suggest that, although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute 1-year risk of intracranial bleeding,” Dr Staerk said.

“Our results complement the large, randomized, phase 3 trials by providing ‘real-world’ data on stroke and intracranial bleeding with NOACs versus warfarin since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials.”

“Registry studies have some limitations, such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head, randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation.”

*Information in the abstract differs from that presented at the meeting.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

ROME—A short-term course of dual antiplatelet therapy (DAPT) may be non-inferior to a longer course in patients who have a certain type of drug-eluting stent (DES), according to research presented at ESC Congress 2016.

Patients in this study, known as NIPPON, had the Nobori bioabsorbable abluminal-coated stent and received 6 months or 18 months of DAPT, which consisted of aspirin plus clopidogrel or ticlopidine.

The results showed similar rates of net adverse clinical and cerebrovascular events, as well as similar rates of bleeding complications, whether patients received DAPT for 6 months or 18 months.

“Based on these findings, a combination of short[-term] DAPT and a newer DES with bioabsorbable abluminal coating should be able to minimize the incidence of thrombotic events and bleeding complications simultaneously,” said Masato Nakamura, MD, PhD, of Toho University Ohashi Medical Center in Tokyo, Japan.

However, Dr Nakamura also noted that this study had limitations, so the results should be interpreted with caution.

Dr Nakamura presented the results at the congress as abstract 2218.

The study enrolled 3775 patients with coronary artery disease or acute myocardial infarction who had undergone percutaneous coronary intervention and stent placement at 130 Japanese institutions.

All patients had received the Nobori bioabsorbable abluminal-coated stent, with DAPT consisting of aspirin (81–162 mg/day) combined with clopidogrel (75 mg/day) or ticlopidine (200 mg/day).

An interim analysis of the study data showed slow enrolment and substantially lower events than expected, so the study was terminated early.

Dr Nakamura presented results from the first 2772 patients to be followed for at least 18 months.

There was no significant difference in the occurrence of the primary endpoint—net adverse clinical and cerebrovascular events—among patients randomized to either short-term or long-term DAPT—1.92% and 1.45%, respectively—confirming the non-inferiority of short-term therapy.

The rate of bleeding events was similar between the treatment arms as well—0.73% in the long-term arm and 0.96% in the short-term arm—as was the rate of stent thrombosis—0.07% in both arms.

“The results of the present study should be interpreted with caution before trying to draw firm conclusions,” Dr Nakamura said. “The interpretation of the NIPPON trial is complicated by the fact that the event rate was lower than the expected incidence of the primary endpoint in both groups. Therefore, the statistical power may not have been adequate to fully assess the risk of [the] primary endpoint.”

Dr Nakamura also noted that the follow-up period may not have been long enough to draw conclusions about the optimum duration of DAPT for patients with DES.

Furthermore, the early termination of the study, in conjunction with the enrollment of relatively low-risk subjects, suggests the study’s results may not be generalizable to high-risk patients. Similarly, as antiplatelet therapy was mainly limited to clopidogrel, the use of more potent antiplatelet agents may have led to different conclusions.

This study was funded by Associations for Establishment of Evidence in Interventions Studies. Dr Nakamura has received research grant support and honoraria from Terumo Corporation, Sanofi, and Daiichi Sankyo.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

The European Society of Cardiology (ESC) has launched a novel position paper, under the auspices of its Committee for Practice Guidelines, on the cardiac toxicity of anticancer therapies.

The paper is a summary and evaluation of relevant scientific evidence that is intended to assist health professionals in selecting the best strategies for preventing and managing cardiac toxicity in patients with cancer, including leukemia, lymphoma, and multiple myeloma.

The paper was published in European Heart Journal and on the ESC website.

The document reviews the potential cardiovascular complications of anticancer therapies.

The complications are divided into 9 categories: myocardial dysfunction and heart failure, coronary artery disease, valvular disease, arrhythmias, arterial hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension, and pericardial complications.

For each type of complication, the authors outline which patients are at risk and how to detect and prevent the possible side effects. Recommendations are given on how to treat and follow patients who develop that type of cardiotoxicity.

Cardiotoxicity is detected using electrocardiogram, cardiac imaging, and biomarkers. Prevention and treatment may involve the use of cardioprotective drugs (such as angiotensin converting enzyme inhibitors or beta-blockers) and adopting a healthy lifestyle (eating a healthy diet, not smoking, exercising regularly, and controlling body weight).

Regarding long-term surveillance for cancer survivors, the paper says patients should be informed of their increased risk of cardiovascular disease at the outset of cancer treatment and supported to make lifestyle changes. They should be told to report early signs and symptoms of cardiovascular disease promptly.

The paper also emphasizes the importance of establishing multidisciplinary teams to provide the best care for cancer patients and survivors. These should include cardiologists, oncologists, nurses, and heart failure and imaging specialists. Ultimately, cardio-oncology centers with a structured service are needed.

The authors note that under- or over-diagnosis of cardiovascular disease sometimes results in failure to prevent adverse events or inappropriate interruption of a potentially life-saving anticancer treatment.

“We need to be clear when it’s a must to stop the treatment, when we should reduce the dose, or when we can continue with the therapy,” said author Jose Luis Zamorano, MD, of University Hospital Ramón in Madrid, Spain. “This position paper provides guidance in this area.”

“We hope the paper will increase awareness about heart disease in cancer patients and survivors and stimulate more research in this area,” added author Patrizio Lancellotti, MD, PhD, of University of Liège Hospital in Liège, Belgium.

“More information is needed on when to screen and monitor patients and on the cardiovascular effects of new anticancer therapies.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

The European Society of Cardiology (ESC) has launched a novel position paper, under the auspices of its Committee for Practice Guidelines, on the cardiac toxicity of anticancer therapies.

The paper is a summary and evaluation of relevant scientific evidence that is intended to assist health professionals in selecting the best strategies for preventing and managing cardiac toxicity in patients with cancer, including leukemia, lymphoma, and multiple myeloma.

The paper was published in European Heart Journal and on the ESC website.

The document reviews the potential cardiovascular complications of anticancer therapies.

The complications are divided into 9 categories: myocardial dysfunction and heart failure, coronary artery disease, valvular disease, arrhythmias, arterial hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension, and pericardial complications.

For each type of complication, the authors outline which patients are at risk and how to detect and prevent the possible side effects. Recommendations are given on how to treat and follow patients who develop that type of cardiotoxicity.

Cardiotoxicity is detected using electrocardiogram, cardiac imaging, and biomarkers. Prevention and treatment may involve the use of cardioprotective drugs (such as angiotensin converting enzyme inhibitors or beta-blockers) and adopting a healthy lifestyle (eating a healthy diet, not smoking, exercising regularly, and controlling body weight).

Regarding long-term surveillance for cancer survivors, the paper says patients should be informed of their increased risk of cardiovascular disease at the outset of cancer treatment and supported to make lifestyle changes. They should be told to report early signs and symptoms of cardiovascular disease promptly.

The paper also emphasizes the importance of establishing multidisciplinary teams to provide the best care for cancer patients and survivors. These should include cardiologists, oncologists, nurses, and heart failure and imaging specialists. Ultimately, cardio-oncology centers with a structured service are needed.

The authors note that under- or over-diagnosis of cardiovascular disease sometimes results in failure to prevent adverse events or inappropriate interruption of a potentially life-saving anticancer treatment.

“We need to be clear when it’s a must to stop the treatment, when we should reduce the dose, or when we can continue with the therapy,” said author Jose Luis Zamorano, MD, of University Hospital Ramón in Madrid, Spain. “This position paper provides guidance in this area.”

“We hope the paper will increase awareness about heart disease in cancer patients and survivors and stimulate more research in this area,” added author Patrizio Lancellotti, MD, PhD, of University of Liège Hospital in Liège, Belgium.

“More information is needed on when to screen and monitor patients and on the cardiovascular effects of new anticancer therapies.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

The European Society of Cardiology (ESC) has launched a novel position paper, under the auspices of its Committee for Practice Guidelines, on the cardiac toxicity of anticancer therapies.

The paper is a summary and evaluation of relevant scientific evidence that is intended to assist health professionals in selecting the best strategies for preventing and managing cardiac toxicity in patients with cancer, including leukemia, lymphoma, and multiple myeloma.

The paper was published in European Heart Journal and on the ESC website.

The document reviews the potential cardiovascular complications of anticancer therapies.

The complications are divided into 9 categories: myocardial dysfunction and heart failure, coronary artery disease, valvular disease, arrhythmias, arterial hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension, and pericardial complications.

For each type of complication, the authors outline which patients are at risk and how to detect and prevent the possible side effects. Recommendations are given on how to treat and follow patients who develop that type of cardiotoxicity.

Cardiotoxicity is detected using electrocardiogram, cardiac imaging, and biomarkers. Prevention and treatment may involve the use of cardioprotective drugs (such as angiotensin converting enzyme inhibitors or beta-blockers) and adopting a healthy lifestyle (eating a healthy diet, not smoking, exercising regularly, and controlling body weight).

Regarding long-term surveillance for cancer survivors, the paper says patients should be informed of their increased risk of cardiovascular disease at the outset of cancer treatment and supported to make lifestyle changes. They should be told to report early signs and symptoms of cardiovascular disease promptly.

The paper also emphasizes the importance of establishing multidisciplinary teams to provide the best care for cancer patients and survivors. These should include cardiologists, oncologists, nurses, and heart failure and imaging specialists. Ultimately, cardio-oncology centers with a structured service are needed.

The authors note that under- or over-diagnosis of cardiovascular disease sometimes results in failure to prevent adverse events or inappropriate interruption of a potentially life-saving anticancer treatment.

“We need to be clear when it’s a must to stop the treatment, when we should reduce the dose, or when we can continue with the therapy,” said author Jose Luis Zamorano, MD, of University Hospital Ramón in Madrid, Spain. “This position paper provides guidance in this area.”

“We hope the paper will increase awareness about heart disease in cancer patients and survivors and stimulate more research in this area,” added author Patrizio Lancellotti, MD, PhD, of University of Liège Hospital in Liège, Belgium.

“More information is needed on when to screen and monitor patients and on the cardiovascular effects of new anticancer therapies.”

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.