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Anticoagulation Hub contains news and clinical review articles for physicians seeking the most up-to-date information on the rapidly evolving treatment options for preventing stroke, acute coronary events, deep vein thrombosis, and pulmonary embolism in at-risk patients. The Anticoagulation Hub is powered by Frontline Medical Communications.
Aspirin use linked to increased ICH in trauma patients
WAIKOLOA, HAWAII – Among a group of anticoagulated trauma patients, those on aspirin had the highest rate and risk of intracranial hemorrhage (ICH), while those on novel oral anticoagulants were not at higher risk for ICH, ICH progression, or death, a multicenter study found.
“The number of patients on warfarin and antiplatelet agents has significantly increased over time,” Leslie Kobayashi, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “These oral antithrombotic agents have been associated with poor outcomes following traumatic injury, including increased rates of intracranial hemorrhage, increased progression of intracranial hemorrhage, and increased mortality.”
In a prospective, multicenter observational study conducted by the AAST’s Multi-institutional Trials Committee, Dr. Kobayashi and her associates set out identify injury patterns and outcomes in trauma patients taking the NOAs, and to test their hypothesis that patients taking NOAs would have higher rates of ICH, ICH progression, and death, compared with patients taking traditional oral anticoagulant therapies (OATs). Patients were included if they were admitted to the trauma service on warfarin, aspirin, clopidogrel, dabigatran, apixaban, or rivaroxaban. Pregnant patients, prisoners, and minors were excluded from the study. Data collected included demographics, mechanism of injury, vitals on admission, injuries/injury severity scores, labs, interventions, and reversal agents used such as vitamin K, prothrombin complexes, dialysis, and transfusion of fresh frozen plasma (FFP). Outcomes studied included ICH, ICH progression, and death.
In all, 16 Level 1 trauma centers enrolled 1,847 patients over a 2-year period. Their average age was 75 years, 46% were female, 77% were white, their median Injury Severity Score (ISS) was 9, and 99% sustained a blunt mechanism of trauma. The top two causes of injury were falls (71%) and motor vehicle crashes (15%). One-third of patients (33%) were on warfarin, while the remainder were on aspirin (26%), clopidogrel (24%), NOAs (10%), and 7% took multiple or other agents.
The mechanism of injury pattern was similar between patients taking NOAs and those taking OATs, with the exception of patients on aspirin being significantly less likely to have sustained a fall. Patients on aspirin also had a significantly higher median ISS. “Patients on NOAs presented more frequently in shock as defined by a systolic blood pressure of less than 90 mmHg, but this was not associated with increased need for packed red blood cell transfusion, bleeding requiring an intervention, need for surgical procedure, hospital LOS, complications, or death,” Dr. Kobayashi said.
About 30% of all patients studied underwent an attempt at reversal. The types of agents used to reverse the patients differed depending on drug agent, with antiplatelet patients more frequently getting platelets, and patients on warfarin more frequently receiving FFP, vitamin K, and prothrombin complex. “Interestingly, patients on the anti-Xa inhibitors more frequently received prothrombin complex as well,” she said. “This likely reflects some of the recent literature which suggests that there may be a therapeutic benefit to using prothrombin complex in patients taking the oral anti-Xa inhibitors but not in patients on dabigatran.”
Overall, bleeding, need for surgical procedure, need for neurosurgical procedure, complications, length of stay, and death were similar between those on NOAs and those on OATs. However, the rate of ICH was significantly higher in patients on aspirin. “What is even more surprising is that 89% of the patients in the aspirin-only group were on an 81-mg baby aspirin rather than the larger 325-mg dose,” Dr. Kobayashi said. This difference was significant on univariate analysis and was retained after multivariate logistic regression adjusted for differences between populations, with an OR for aspirin of 1.7 and a P value of .024. “This is not to suggest that patients on aspirin are doing markedly worse, compared to their counterparts, but I think most of us would have assumed that aspirin patients would have done better,” she commented. “I think we’ve definitively shown that is not the case.” Other independent predictors of ICH were advanced age (OR, 1.02), Asian race (OR, 3.1), ISS of 10 or greater (OR, 2.2), and a Glasgow coma score (GCS) of 8 or less (OR, 5.6).
Despite their increased risk for ICH, patients on aspirin were significantly less likely to undergo an attempt at reversal with any type of agent, at 16% with a P value of less than .001, on univariate analysis. “This was significantly lower than all other medications and was retained after multivariate logistic regression, with an OR of 0.3 and a P value of less than .001,” she said.
Progression of ICH did not differ by medication group. Other independent predictors included intraparenchymal location of hemorrhage (OR, 2.2), need for a neurosurgical procedure (OR, 5.1), an attempt at reversal (OR, 2.3) and a GCS of 8 or lower at admission (OR, 4.3). Similarly, multivariate analysis of death showed no significant differences between the different medication groups. Independent predictors included advanced age (OR, 1.06), GCS of 8 or less (OR, 13), progression of head injury (OR, 10), bleeding (OR, 2.3), and complications (OR, 2.1).
Dr. Kobayashi acknowledged that the study’s observational design is a limitation, as well as the fact that it lacked a control group of age-matched patients who were not taking anticoagulants. “Additionally, we had a relatively low number of patients on NOAs, at only 10% of the study population,” she said. “Lastly, there is potential for enrollment bias as all sites involved in this study were level one trauma centers.” She reported having no financial disclosures.
WAIKOLOA, HAWAII – Among a group of anticoagulated trauma patients, those on aspirin had the highest rate and risk of intracranial hemorrhage (ICH), while those on novel oral anticoagulants were not at higher risk for ICH, ICH progression, or death, a multicenter study found.
“The number of patients on warfarin and antiplatelet agents has significantly increased over time,” Leslie Kobayashi, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “These oral antithrombotic agents have been associated with poor outcomes following traumatic injury, including increased rates of intracranial hemorrhage, increased progression of intracranial hemorrhage, and increased mortality.”
In a prospective, multicenter observational study conducted by the AAST’s Multi-institutional Trials Committee, Dr. Kobayashi and her associates set out identify injury patterns and outcomes in trauma patients taking the NOAs, and to test their hypothesis that patients taking NOAs would have higher rates of ICH, ICH progression, and death, compared with patients taking traditional oral anticoagulant therapies (OATs). Patients were included if they were admitted to the trauma service on warfarin, aspirin, clopidogrel, dabigatran, apixaban, or rivaroxaban. Pregnant patients, prisoners, and minors were excluded from the study. Data collected included demographics, mechanism of injury, vitals on admission, injuries/injury severity scores, labs, interventions, and reversal agents used such as vitamin K, prothrombin complexes, dialysis, and transfusion of fresh frozen plasma (FFP). Outcomes studied included ICH, ICH progression, and death.
In all, 16 Level 1 trauma centers enrolled 1,847 patients over a 2-year period. Their average age was 75 years, 46% were female, 77% were white, their median Injury Severity Score (ISS) was 9, and 99% sustained a blunt mechanism of trauma. The top two causes of injury were falls (71%) and motor vehicle crashes (15%). One-third of patients (33%) were on warfarin, while the remainder were on aspirin (26%), clopidogrel (24%), NOAs (10%), and 7% took multiple or other agents.
The mechanism of injury pattern was similar between patients taking NOAs and those taking OATs, with the exception of patients on aspirin being significantly less likely to have sustained a fall. Patients on aspirin also had a significantly higher median ISS. “Patients on NOAs presented more frequently in shock as defined by a systolic blood pressure of less than 90 mmHg, but this was not associated with increased need for packed red blood cell transfusion, bleeding requiring an intervention, need for surgical procedure, hospital LOS, complications, or death,” Dr. Kobayashi said.
About 30% of all patients studied underwent an attempt at reversal. The types of agents used to reverse the patients differed depending on drug agent, with antiplatelet patients more frequently getting platelets, and patients on warfarin more frequently receiving FFP, vitamin K, and prothrombin complex. “Interestingly, patients on the anti-Xa inhibitors more frequently received prothrombin complex as well,” she said. “This likely reflects some of the recent literature which suggests that there may be a therapeutic benefit to using prothrombin complex in patients taking the oral anti-Xa inhibitors but not in patients on dabigatran.”
Overall, bleeding, need for surgical procedure, need for neurosurgical procedure, complications, length of stay, and death were similar between those on NOAs and those on OATs. However, the rate of ICH was significantly higher in patients on aspirin. “What is even more surprising is that 89% of the patients in the aspirin-only group were on an 81-mg baby aspirin rather than the larger 325-mg dose,” Dr. Kobayashi said. This difference was significant on univariate analysis and was retained after multivariate logistic regression adjusted for differences between populations, with an OR for aspirin of 1.7 and a P value of .024. “This is not to suggest that patients on aspirin are doing markedly worse, compared to their counterparts, but I think most of us would have assumed that aspirin patients would have done better,” she commented. “I think we’ve definitively shown that is not the case.” Other independent predictors of ICH were advanced age (OR, 1.02), Asian race (OR, 3.1), ISS of 10 or greater (OR, 2.2), and a Glasgow coma score (GCS) of 8 or less (OR, 5.6).
Despite their increased risk for ICH, patients on aspirin were significantly less likely to undergo an attempt at reversal with any type of agent, at 16% with a P value of less than .001, on univariate analysis. “This was significantly lower than all other medications and was retained after multivariate logistic regression, with an OR of 0.3 and a P value of less than .001,” she said.
Progression of ICH did not differ by medication group. Other independent predictors included intraparenchymal location of hemorrhage (OR, 2.2), need for a neurosurgical procedure (OR, 5.1), an attempt at reversal (OR, 2.3) and a GCS of 8 or lower at admission (OR, 4.3). Similarly, multivariate analysis of death showed no significant differences between the different medication groups. Independent predictors included advanced age (OR, 1.06), GCS of 8 or less (OR, 13), progression of head injury (OR, 10), bleeding (OR, 2.3), and complications (OR, 2.1).
Dr. Kobayashi acknowledged that the study’s observational design is a limitation, as well as the fact that it lacked a control group of age-matched patients who were not taking anticoagulants. “Additionally, we had a relatively low number of patients on NOAs, at only 10% of the study population,” she said. “Lastly, there is potential for enrollment bias as all sites involved in this study were level one trauma centers.” She reported having no financial disclosures.
WAIKOLOA, HAWAII – Among a group of anticoagulated trauma patients, those on aspirin had the highest rate and risk of intracranial hemorrhage (ICH), while those on novel oral anticoagulants were not at higher risk for ICH, ICH progression, or death, a multicenter study found.
“The number of patients on warfarin and antiplatelet agents has significantly increased over time,” Leslie Kobayashi, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “These oral antithrombotic agents have been associated with poor outcomes following traumatic injury, including increased rates of intracranial hemorrhage, increased progression of intracranial hemorrhage, and increased mortality.”
In a prospective, multicenter observational study conducted by the AAST’s Multi-institutional Trials Committee, Dr. Kobayashi and her associates set out identify injury patterns and outcomes in trauma patients taking the NOAs, and to test their hypothesis that patients taking NOAs would have higher rates of ICH, ICH progression, and death, compared with patients taking traditional oral anticoagulant therapies (OATs). Patients were included if they were admitted to the trauma service on warfarin, aspirin, clopidogrel, dabigatran, apixaban, or rivaroxaban. Pregnant patients, prisoners, and minors were excluded from the study. Data collected included demographics, mechanism of injury, vitals on admission, injuries/injury severity scores, labs, interventions, and reversal agents used such as vitamin K, prothrombin complexes, dialysis, and transfusion of fresh frozen plasma (FFP). Outcomes studied included ICH, ICH progression, and death.
In all, 16 Level 1 trauma centers enrolled 1,847 patients over a 2-year period. Their average age was 75 years, 46% were female, 77% were white, their median Injury Severity Score (ISS) was 9, and 99% sustained a blunt mechanism of trauma. The top two causes of injury were falls (71%) and motor vehicle crashes (15%). One-third of patients (33%) were on warfarin, while the remainder were on aspirin (26%), clopidogrel (24%), NOAs (10%), and 7% took multiple or other agents.
The mechanism of injury pattern was similar between patients taking NOAs and those taking OATs, with the exception of patients on aspirin being significantly less likely to have sustained a fall. Patients on aspirin also had a significantly higher median ISS. “Patients on NOAs presented more frequently in shock as defined by a systolic blood pressure of less than 90 mmHg, but this was not associated with increased need for packed red blood cell transfusion, bleeding requiring an intervention, need for surgical procedure, hospital LOS, complications, or death,” Dr. Kobayashi said.
About 30% of all patients studied underwent an attempt at reversal. The types of agents used to reverse the patients differed depending on drug agent, with antiplatelet patients more frequently getting platelets, and patients on warfarin more frequently receiving FFP, vitamin K, and prothrombin complex. “Interestingly, patients on the anti-Xa inhibitors more frequently received prothrombin complex as well,” she said. “This likely reflects some of the recent literature which suggests that there may be a therapeutic benefit to using prothrombin complex in patients taking the oral anti-Xa inhibitors but not in patients on dabigatran.”
Overall, bleeding, need for surgical procedure, need for neurosurgical procedure, complications, length of stay, and death were similar between those on NOAs and those on OATs. However, the rate of ICH was significantly higher in patients on aspirin. “What is even more surprising is that 89% of the patients in the aspirin-only group were on an 81-mg baby aspirin rather than the larger 325-mg dose,” Dr. Kobayashi said. This difference was significant on univariate analysis and was retained after multivariate logistic regression adjusted for differences between populations, with an OR for aspirin of 1.7 and a P value of .024. “This is not to suggest that patients on aspirin are doing markedly worse, compared to their counterparts, but I think most of us would have assumed that aspirin patients would have done better,” she commented. “I think we’ve definitively shown that is not the case.” Other independent predictors of ICH were advanced age (OR, 1.02), Asian race (OR, 3.1), ISS of 10 or greater (OR, 2.2), and a Glasgow coma score (GCS) of 8 or less (OR, 5.6).
Despite their increased risk for ICH, patients on aspirin were significantly less likely to undergo an attempt at reversal with any type of agent, at 16% with a P value of less than .001, on univariate analysis. “This was significantly lower than all other medications and was retained after multivariate logistic regression, with an OR of 0.3 and a P value of less than .001,” she said.
Progression of ICH did not differ by medication group. Other independent predictors included intraparenchymal location of hemorrhage (OR, 2.2), need for a neurosurgical procedure (OR, 5.1), an attempt at reversal (OR, 2.3) and a GCS of 8 or lower at admission (OR, 4.3). Similarly, multivariate analysis of death showed no significant differences between the different medication groups. Independent predictors included advanced age (OR, 1.06), GCS of 8 or less (OR, 13), progression of head injury (OR, 10), bleeding (OR, 2.3), and complications (OR, 2.1).
Dr. Kobayashi acknowledged that the study’s observational design is a limitation, as well as the fact that it lacked a control group of age-matched patients who were not taking anticoagulants. “Additionally, we had a relatively low number of patients on NOAs, at only 10% of the study population,” she said. “Lastly, there is potential for enrollment bias as all sites involved in this study were level one trauma centers.” She reported having no financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point:
Major finding: The rate of ICH was significantly higher in patients on aspirin, compared with those on novel oral anticoagulant therapies (OR, 1.7; P = .024).
Data source: A prospective evaluation of 1,847 patients treated at 16 level one trauma centers over a 2-year period.
Disclosures: Dr. Kobayashi reported having no financial disclosures.
Recovery path complicated for trauma patients with VTE
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.” 
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.”
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.”
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
AT WSA 2016
Key clinical point:
Major finding: Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Data source: A secondary analysis of 558 patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells.
Disclosures: The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
PPIs may boost ischemic stroke risk
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
A growing number of retrospective studies have associated proton pump inhibitors with a host of serious adverse effects. These include chronic kidney disease, dementia, osteoporosis, cardiovascular events, pneumonia, enteric infections, and others. The authors of this large, retrospective Danish study have now added ischemic stroke to the list.
Nonetheless, this study should serve as wake-up call to closely examine the risks and benefits of ongoing PPI use for each individual patient. For example, guidelines clearly advocate the use of PPIs in patients at high risk for peptic ulcer disease (for example, use of aspirin and warfarin together), and these patients should continue PPIs unless more convincing evidence of serious side effects emerge. On the other hand, several studies have shown that many patients with uncomplicated gastroesophageal reflux disease symptoms can achieve symptom control with substitution of histamine2 blockers, p.r.n. dosing of PPIs, or without acid-reducing medications entirely. Still, many patients with confirmed pathologic acid reflux are likely to require ongoing PPIs. For patients who continue PPIs, they should use the lowest effective dose.
Surely, physicians will be discussing PPI adverse effects with increasing numbers of patients. Until higher-quality evidence in the form of a randomized controlled trial emerges, physicians should get used to explaining the principles of epidemiology.
Jacob Kurlander, MD, is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor. He has received research funding from Ironwood Pharmaceuticals.
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
NEW ORLEANS – The use of proton pump inhibitors (PPIs) was associated with significantly increased risk of having a first ischemic stroke in a large nationwide Danish cohort study, Thomas S. Sehested, MD, reported at the American Heart Association scientific sessions.
The relationship was dose dependent. At the lowest available dose of each of the four PPIs studied there was no significantly increased risk. At the intermediate doses of three of the four PPIs studied, the increased risk of ischemic stroke became statistically significant. And the highest dose of each drug was associated with the greatest ischemic stroke risk.
In Denmark, for instance, where most PPIs are prescription only and use is easily trackable, it’s estimated that, at any given time, 7% of the adult population is taking a PPI, often not as directed in the labeling.
The impetus for this study, Dr. Sehested explained, was the mounting evidence that PPIs may constitute an independent risk factor for acute MI and other cardiovascular events. For example, a recent meta-analysis of 17 randomized controlled trials totaling 7,540 participants published through mid-2015 concluded that the use of PPIs was associated with a 70% increase in cardiovascular risk (Neurogastroenterol Motil. 2016 Aug 30. doi: 10.1111/nmo.12926).
He reported on 245,676 Danes above age 30 who were free of prior MI or stroke when they underwent elective GI endoscopy during 1997-2012. After a 30-day postendoscopy grace period during which 1,476 patients had a first MI, stroke, or died of any cause, the final study population was 244,200, of whom 43.7% were PPI users during the grace period and beyond.
During a median 5.8 years of follow-up, 9,489 subjects (3.9%) had a first ischemic stroke. Because of the comprehensive nature of Denmark’s interlocking birth to death registries, there was virtually no loss to follow-up in this study.
The unadjusted incidence of ischemic stroke in PPI nonusers was 55.7 per 10,000 person-years, compared with 88.9 per 10,000 in PPI users.
The PPI users were slightly older than nonusers by roughly 3 years. They were also an absolute 5% more likely to be hypertensive and an absolute 1.7% more likely to be regular users of NSAIDs. All of these differences, while modest, were statistically significant because of the large patient numbers involved.
In a multivariate analysis adjusted for age, sex, calendar year, comorbid diabetes, hypertension, alcohol use disorder, heart failure, peptic ulcer, peripheral artery disease, kidney disease, aspirin, oral anticoagulants and other medications, and socioeconomic status, current users of PPIs were 19% more likely to have a first ischemic stroke than nonusers. That difference is statistically significant and clinically meaningful, Dr. Sehested said.
In contrast, when the same sort of nationwide analysis was repeated, comparing current users of histamine-2 receptor antagonists to nonusers of those drugs or PPIs, there was no difference in ischemic stroke risk between the two groups.
The message, according to Dr. Sehested, is that physicians should encourage more cautious use of PPIs. And especially in the United States, where most PPIs are available over the counter, it’s prudent during office visits to ask what nonprescription drugs a patient is taking.
Dr. Sehested presented his study findings in a session devoted to original research in cardiovascular epidemiology. Many top American epidemiologists were present in the audience, and several rose to congratulate him on his presentation of the latest elegant epidemiologic study to come out of Denmark, the only place in the world where this sort of nationwide comprehensive research is possible.
“Wow! I just love the work you do in Denmark. It’s really inspiring,” commented David Siscovick, MD, senior vice president for research at the New York Academy of Medicine and professor emeritus of medicine and epidemiology at the University of Washington in Seattle.
He had a question: “Did you deal with PPI starters and stoppers and compliance in any way?”
Dr. Sehested replied that he and his coinvestigators were able to see who was on a PPI at any given point in the study, and they accounted for that. One issue the researchers plan to examine but haven’t yet had a chance to, however, is the relationship between duration of PPI therapy and ischemic stroke risk. It’s likely that some patients had already been on a PPI for a lengthy time at elective endoscopy, which is when the study in its current form began.
“I think that would strengthen the study,” he said.
Comoderator Jorge Kizer, MD, of Albert Einstein College of Medicine in New York, commented, “Confounding by indication is clearly the elephant in the room. The guidelines actually recommend adding a PPI if a patient is on dual-antiplatelet therapy and has an NSAID added. Did you adjust for that? It would boost confidence that the results are actually due to the PPI.”
Dr. Sehested answered that the great majority of individuals with cardiovascular disease at baseline were excluded from the analysis.
“I don’t think we had that many on dual-antiplatelet therapy,” he added.
Preclinical studies suggest a possible mechanism by which PPIs may harm cardiovascular health. The drugs reduce nitric oxide synthase levels, with resultant endothelial dysfunction, he said.
Dr. Sehested is employed at the Danish Heart Foundation, which funded the study.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Current use of a proton pump inhibitor was independently associated with a 19% increased risk of a first ischemic stroke, and the risk was greater at the top approved doses.
Data source: This retrospective nationwide Danish study involved 244,200 adults age 30 or older followed for a median of nearly 6 years following elective GI endoscopy.
Disclosures: The presenter is employed at the Danish Heart Foundation, which funded the study.
Initial outcomes of PERT at Cleveland Clinic
LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.
Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.
The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.
The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.
Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.
Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.
The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.
Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).
The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.
The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.
Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.
Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.
The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”
Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”
Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.
Dr. Mahar reported no disclosures.
Mary Jo Dales contributed to this report.
LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.
Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.
The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.
The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.
Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.
Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.
The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.
Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).
The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.
The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.
Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.
Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.
The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”
Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”
Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.
Dr. Mahar reported no disclosures.
Mary Jo Dales contributed to this report.
LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.
Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.
The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.
The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.
Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.
Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.
The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.
Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).
The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.
The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.
Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.
Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.
The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”
Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”
Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.
Dr. Mahar reported no disclosures.
Mary Jo Dales contributed to this report.
FROM CHEST 2016
VIDEO: Rivaroxaban gives safer protection to atrial fib patients post PCI
NEW ORLEANS – The puzzle of how to safely prevent thrombotic events in patients with atrial fibrillation who receive a coronary stent now has a little more clarity in the era of new oral anticoagulants.
The first randomized trial to compare the safety of a new oral anticoagulant (NOAC, in this case rivaroxaban) against warfarin when paired with one or more antiplatelet drugs showed that the NOAC edged out warfarin for safety by cutting the rate of clinically significant bleeding events while preventing thrombotic events roughly as well as warfarin.
Despite that, the incidence of all major adverse coronary events during the 1-year follow-up was virtually identical in the three groups, ranging from 5.6% to 6.5%, with very low rates of stroke in the three treatment arms, ranging from 1.2%-1.5%, said Dr. Gibson, a professor of medicine at Harvard Medical School and an interventional cardiologist at Beth Israel Deaconess Medical Center, both in Boston.
These results “are a huge step forward and will change practice,” commented Philippe Gabriel Steg, MD, discussant for the report and director of the coronary care unit of Bichat Hospital in Paris. “We’ve gone from having no evidence to having some evidence” for using a NOAC in this setting. “It was a difficult but very important study that truly advances the field.”
The trial randomized patients to any of three main treatment regimens: 2.5 mg rivaroxaban b.i.d., 15 mg rivaroxaban once daily, or warfarin taken to maintain an international normalized ratio of 2.0-3.0. During the study, patients in the warfarin arm were in this therapeutic range 65% of the time.
The trial’s design instructed physicians to treat patients who received the lower rivaroxaban dosage to also administer aspirin (75-100 mg daily) plus a thienopyridine of their choice. Patients on the higher rivaroxaban dosage received monotherapy with a thienopyridine of the physician’s choosing, while patients assigned to receive warfarin were also to get aspirin (75-100 mg daily) and a thienopyridine. It turned out that in each of the three treatment arms, 95% of patients received clopidogrel, 4% received ticagrelor (Brilinta), and 1% received prasugrel (Effient).
The trial also left it up to each physician to decide how long each patient should remain on dual antiplatelet therapy. In each of the two treatment arms that used dual therapy, 49% received 12 months of dual treatment, 35% received it for 6 months, and 16% received it for 1 month. Once the period of dual therapy ended, patients continued to receive aspirin (at 75-100 mg/day) for the balance of the 12-month study.
Leaving the choice of thienopyridine and duration of dual therapy up to each physician helped make this a “real world study,” Dr. Gibson said.
The trial was fully powered to prove a difference in safety based on rates of clinically significant bleeding events. The 1-year rates were 17% in patients who received 15 mg of rivaroxaban daily, 18% in those who received 2.5 mg rivaroxaban b.i.d., and 27% in the patients on warfarin: statistically significant differences between the warfarin arm and each of the two rivaroxaban arms. The study was not powered to prove noninferiority of the rivaroxaban regimens for efficacy at preventing stroke or major adverse events (cardiovascular death, MI, or stroke). To do that would require a trial with more than 30,000 patients, Dr. Gibson noted.
Also concurrently with Dr. Gibson’s report, a second article was published online with a post-hoc efficacy analysis that used as an efficacy endpoint the combined 1-year rate of death and all-cause hospitalization for an adverse event (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025783). In this analysis, each of the two rivaroxaban arms cut the rate of this outcome by about 25% relative to the patients treated with warfarin, statistically significant differences. Both of the rivaroxaban regimens led to significant reductions in hospitalizations both for cardiovascular events and for bleeding events, Dr. Gibson reported.
He speculated that the vast majority of patients in the study wound up receiving clopidogrel because of cost consideration, because many physicians weren’t comfortable pairing a more potent thienopyridine with an anticoagulant, and because clopidogrel remains the most commonly used agent from this class in many parts of the world.
Dr. Gibson suggested that physicians who use these rivaroxaban-based regimens in routine practice tailor their thienopyridine selection and the duration of dual therapy to each patient based on these factors as well as whether the individual patient appears to face a greater danger from bleeding or from an ischemic event. The same approach should also guide choosing between the two rivaroxaban regimens tested. The 2.5-mg b.i.d. dosage used in a triple-therapy strategy that combines it with aspirin and a thienopyridine is better suited to patients at higher risk for ischemic events, while the 15-mg once daily dosage coupled with a thienopyridine but without aspirin is better suited to patients with a high bleeding risk, he said in an interview. Because the 2.5-mg formulation is not currently available for U.S. sales, most American physicians will be limited to only prescribing 15 mg of rivaroxaban daily. And for patients with very poor renal function, with a creatinine clearance rate of less than 15 mL/min, warfarin remains the best option, Dr. Gibson said.
PIONEER AF-PCI was sponsored by Johnson & Johnson (Janssen) and Bayer, the two companies that market rivaroxaban (Xarelto) worldwide. Dr. Gibson has received research support from and has been a consultant to Johnson & Johnson and Bayer and has also received research support and consulted for several other drug companies. Dr. Steg has been a consultant to Bayer and Janssen, and has received research support from or has been a consultant to several other drug companies.
[email protected]
On Twitter @mitchelzoler
The results from PIONEER AF-PCI give us important and helpful information now that physicians increasingly prescribe a new oral anticoagulant to treat patients with nonvalvular atrial fibrillation. The trial provides strong evidence that one or two antiplatelet drugs can safely be combined with rivaroxaban when these patients undergo coronary stenting.
Until now, the only data we had on the safety and efficacy of combining an anticoagulant with one or more antiplatelet drugs in these patients involved warfarin-based regimens. Because of this limitation, some clinicians even switched atrial fibrillation patients who were on a new oral anticoagulant to warfarin if they received a coronary stent and therefore needed treatment with antiplatelet drugs.
The study results show that the rivaroxaban-based regimens were safe, even safer than the warfarin-based strategy, and there was no signal of harm in the form on increased strokes or stent thrombosis. Because of the study’s complex design, with many different regimens that included various thienopyridines and various durations of antiplatelet treatment, it is hard to decide from just these results the best approach among all the different combinations tested. But the PIONEER AF-PCI results start to build a data platform for the new oral anticoagulants that clinicians can use to help guide management of these patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Richard C. Becker, MD, is professor of medicine and director of the Heart, Lung and Vascular Institute at the University of Cincinnati. He has received research support from AstraZeneca and Janssen. He made these comments in an interview.
The results from PIONEER AF-PCI give us important and helpful information now that physicians increasingly prescribe a new oral anticoagulant to treat patients with nonvalvular atrial fibrillation. The trial provides strong evidence that one or two antiplatelet drugs can safely be combined with rivaroxaban when these patients undergo coronary stenting.
Until now, the only data we had on the safety and efficacy of combining an anticoagulant with one or more antiplatelet drugs in these patients involved warfarin-based regimens. Because of this limitation, some clinicians even switched atrial fibrillation patients who were on a new oral anticoagulant to warfarin if they received a coronary stent and therefore needed treatment with antiplatelet drugs.
The study results show that the rivaroxaban-based regimens were safe, even safer than the warfarin-based strategy, and there was no signal of harm in the form on increased strokes or stent thrombosis. Because of the study’s complex design, with many different regimens that included various thienopyridines and various durations of antiplatelet treatment, it is hard to decide from just these results the best approach among all the different combinations tested. But the PIONEER AF-PCI results start to build a data platform for the new oral anticoagulants that clinicians can use to help guide management of these patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Richard C. Becker, MD, is professor of medicine and director of the Heart, Lung and Vascular Institute at the University of Cincinnati. He has received research support from AstraZeneca and Janssen. He made these comments in an interview.
The results from PIONEER AF-PCI give us important and helpful information now that physicians increasingly prescribe a new oral anticoagulant to treat patients with nonvalvular atrial fibrillation. The trial provides strong evidence that one or two antiplatelet drugs can safely be combined with rivaroxaban when these patients undergo coronary stenting.
Until now, the only data we had on the safety and efficacy of combining an anticoagulant with one or more antiplatelet drugs in these patients involved warfarin-based regimens. Because of this limitation, some clinicians even switched atrial fibrillation patients who were on a new oral anticoagulant to warfarin if they received a coronary stent and therefore needed treatment with antiplatelet drugs.
The study results show that the rivaroxaban-based regimens were safe, even safer than the warfarin-based strategy, and there was no signal of harm in the form on increased strokes or stent thrombosis. Because of the study’s complex design, with many different regimens that included various thienopyridines and various durations of antiplatelet treatment, it is hard to decide from just these results the best approach among all the different combinations tested. But the PIONEER AF-PCI results start to build a data platform for the new oral anticoagulants that clinicians can use to help guide management of these patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Richard C. Becker, MD, is professor of medicine and director of the Heart, Lung and Vascular Institute at the University of Cincinnati. He has received research support from AstraZeneca and Janssen. He made these comments in an interview.
NEW ORLEANS – The puzzle of how to safely prevent thrombotic events in patients with atrial fibrillation who receive a coronary stent now has a little more clarity in the era of new oral anticoagulants.
The first randomized trial to compare the safety of a new oral anticoagulant (NOAC, in this case rivaroxaban) against warfarin when paired with one or more antiplatelet drugs showed that the NOAC edged out warfarin for safety by cutting the rate of clinically significant bleeding events while preventing thrombotic events roughly as well as warfarin.
Despite that, the incidence of all major adverse coronary events during the 1-year follow-up was virtually identical in the three groups, ranging from 5.6% to 6.5%, with very low rates of stroke in the three treatment arms, ranging from 1.2%-1.5%, said Dr. Gibson, a professor of medicine at Harvard Medical School and an interventional cardiologist at Beth Israel Deaconess Medical Center, both in Boston.
These results “are a huge step forward and will change practice,” commented Philippe Gabriel Steg, MD, discussant for the report and director of the coronary care unit of Bichat Hospital in Paris. “We’ve gone from having no evidence to having some evidence” for using a NOAC in this setting. “It was a difficult but very important study that truly advances the field.”
The trial randomized patients to any of three main treatment regimens: 2.5 mg rivaroxaban b.i.d., 15 mg rivaroxaban once daily, or warfarin taken to maintain an international normalized ratio of 2.0-3.0. During the study, patients in the warfarin arm were in this therapeutic range 65% of the time.
The trial’s design instructed physicians to treat patients who received the lower rivaroxaban dosage to also administer aspirin (75-100 mg daily) plus a thienopyridine of their choice. Patients on the higher rivaroxaban dosage received monotherapy with a thienopyridine of the physician’s choosing, while patients assigned to receive warfarin were also to get aspirin (75-100 mg daily) and a thienopyridine. It turned out that in each of the three treatment arms, 95% of patients received clopidogrel, 4% received ticagrelor (Brilinta), and 1% received prasugrel (Effient).
The trial also left it up to each physician to decide how long each patient should remain on dual antiplatelet therapy. In each of the two treatment arms that used dual therapy, 49% received 12 months of dual treatment, 35% received it for 6 months, and 16% received it for 1 month. Once the period of dual therapy ended, patients continued to receive aspirin (at 75-100 mg/day) for the balance of the 12-month study.
Leaving the choice of thienopyridine and duration of dual therapy up to each physician helped make this a “real world study,” Dr. Gibson said.
The trial was fully powered to prove a difference in safety based on rates of clinically significant bleeding events. The 1-year rates were 17% in patients who received 15 mg of rivaroxaban daily, 18% in those who received 2.5 mg rivaroxaban b.i.d., and 27% in the patients on warfarin: statistically significant differences between the warfarin arm and each of the two rivaroxaban arms. The study was not powered to prove noninferiority of the rivaroxaban regimens for efficacy at preventing stroke or major adverse events (cardiovascular death, MI, or stroke). To do that would require a trial with more than 30,000 patients, Dr. Gibson noted.
Also concurrently with Dr. Gibson’s report, a second article was published online with a post-hoc efficacy analysis that used as an efficacy endpoint the combined 1-year rate of death and all-cause hospitalization for an adverse event (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025783). In this analysis, each of the two rivaroxaban arms cut the rate of this outcome by about 25% relative to the patients treated with warfarin, statistically significant differences. Both of the rivaroxaban regimens led to significant reductions in hospitalizations both for cardiovascular events and for bleeding events, Dr. Gibson reported.
He speculated that the vast majority of patients in the study wound up receiving clopidogrel because of cost consideration, because many physicians weren’t comfortable pairing a more potent thienopyridine with an anticoagulant, and because clopidogrel remains the most commonly used agent from this class in many parts of the world.
Dr. Gibson suggested that physicians who use these rivaroxaban-based regimens in routine practice tailor their thienopyridine selection and the duration of dual therapy to each patient based on these factors as well as whether the individual patient appears to face a greater danger from bleeding or from an ischemic event. The same approach should also guide choosing between the two rivaroxaban regimens tested. The 2.5-mg b.i.d. dosage used in a triple-therapy strategy that combines it with aspirin and a thienopyridine is better suited to patients at higher risk for ischemic events, while the 15-mg once daily dosage coupled with a thienopyridine but without aspirin is better suited to patients with a high bleeding risk, he said in an interview. Because the 2.5-mg formulation is not currently available for U.S. sales, most American physicians will be limited to only prescribing 15 mg of rivaroxaban daily. And for patients with very poor renal function, with a creatinine clearance rate of less than 15 mL/min, warfarin remains the best option, Dr. Gibson said.
PIONEER AF-PCI was sponsored by Johnson & Johnson (Janssen) and Bayer, the two companies that market rivaroxaban (Xarelto) worldwide. Dr. Gibson has received research support from and has been a consultant to Johnson & Johnson and Bayer and has also received research support and consulted for several other drug companies. Dr. Steg has been a consultant to Bayer and Janssen, and has received research support from or has been a consultant to several other drug companies.
[email protected]
On Twitter @mitchelzoler
NEW ORLEANS – The puzzle of how to safely prevent thrombotic events in patients with atrial fibrillation who receive a coronary stent now has a little more clarity in the era of new oral anticoagulants.
The first randomized trial to compare the safety of a new oral anticoagulant (NOAC, in this case rivaroxaban) against warfarin when paired with one or more antiplatelet drugs showed that the NOAC edged out warfarin for safety by cutting the rate of clinically significant bleeding events while preventing thrombotic events roughly as well as warfarin.
Despite that, the incidence of all major adverse coronary events during the 1-year follow-up was virtually identical in the three groups, ranging from 5.6% to 6.5%, with very low rates of stroke in the three treatment arms, ranging from 1.2%-1.5%, said Dr. Gibson, a professor of medicine at Harvard Medical School and an interventional cardiologist at Beth Israel Deaconess Medical Center, both in Boston.
These results “are a huge step forward and will change practice,” commented Philippe Gabriel Steg, MD, discussant for the report and director of the coronary care unit of Bichat Hospital in Paris. “We’ve gone from having no evidence to having some evidence” for using a NOAC in this setting. “It was a difficult but very important study that truly advances the field.”
The trial randomized patients to any of three main treatment regimens: 2.5 mg rivaroxaban b.i.d., 15 mg rivaroxaban once daily, or warfarin taken to maintain an international normalized ratio of 2.0-3.0. During the study, patients in the warfarin arm were in this therapeutic range 65% of the time.
The trial’s design instructed physicians to treat patients who received the lower rivaroxaban dosage to also administer aspirin (75-100 mg daily) plus a thienopyridine of their choice. Patients on the higher rivaroxaban dosage received monotherapy with a thienopyridine of the physician’s choosing, while patients assigned to receive warfarin were also to get aspirin (75-100 mg daily) and a thienopyridine. It turned out that in each of the three treatment arms, 95% of patients received clopidogrel, 4% received ticagrelor (Brilinta), and 1% received prasugrel (Effient).
The trial also left it up to each physician to decide how long each patient should remain on dual antiplatelet therapy. In each of the two treatment arms that used dual therapy, 49% received 12 months of dual treatment, 35% received it for 6 months, and 16% received it for 1 month. Once the period of dual therapy ended, patients continued to receive aspirin (at 75-100 mg/day) for the balance of the 12-month study.
Leaving the choice of thienopyridine and duration of dual therapy up to each physician helped make this a “real world study,” Dr. Gibson said.
The trial was fully powered to prove a difference in safety based on rates of clinically significant bleeding events. The 1-year rates were 17% in patients who received 15 mg of rivaroxaban daily, 18% in those who received 2.5 mg rivaroxaban b.i.d., and 27% in the patients on warfarin: statistically significant differences between the warfarin arm and each of the two rivaroxaban arms. The study was not powered to prove noninferiority of the rivaroxaban regimens for efficacy at preventing stroke or major adverse events (cardiovascular death, MI, or stroke). To do that would require a trial with more than 30,000 patients, Dr. Gibson noted.
Also concurrently with Dr. Gibson’s report, a second article was published online with a post-hoc efficacy analysis that used as an efficacy endpoint the combined 1-year rate of death and all-cause hospitalization for an adverse event (Circulation. 2016 Nov 14. doi: 10.1161/CIRCULATIONAHA.116.025783). In this analysis, each of the two rivaroxaban arms cut the rate of this outcome by about 25% relative to the patients treated with warfarin, statistically significant differences. Both of the rivaroxaban regimens led to significant reductions in hospitalizations both for cardiovascular events and for bleeding events, Dr. Gibson reported.
He speculated that the vast majority of patients in the study wound up receiving clopidogrel because of cost consideration, because many physicians weren’t comfortable pairing a more potent thienopyridine with an anticoagulant, and because clopidogrel remains the most commonly used agent from this class in many parts of the world.
Dr. Gibson suggested that physicians who use these rivaroxaban-based regimens in routine practice tailor their thienopyridine selection and the duration of dual therapy to each patient based on these factors as well as whether the individual patient appears to face a greater danger from bleeding or from an ischemic event. The same approach should also guide choosing between the two rivaroxaban regimens tested. The 2.5-mg b.i.d. dosage used in a triple-therapy strategy that combines it with aspirin and a thienopyridine is better suited to patients at higher risk for ischemic events, while the 15-mg once daily dosage coupled with a thienopyridine but without aspirin is better suited to patients with a high bleeding risk, he said in an interview. Because the 2.5-mg formulation is not currently available for U.S. sales, most American physicians will be limited to only prescribing 15 mg of rivaroxaban daily. And for patients with very poor renal function, with a creatinine clearance rate of less than 15 mL/min, warfarin remains the best option, Dr. Gibson said.
PIONEER AF-PCI was sponsored by Johnson & Johnson (Janssen) and Bayer, the two companies that market rivaroxaban (Xarelto) worldwide. Dr. Gibson has received research support from and has been a consultant to Johnson & Johnson and Bayer and has also received research support and consulted for several other drug companies. Dr. Steg has been a consultant to Bayer and Janssen, and has received research support from or has been a consultant to several other drug companies.
[email protected]
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: The two tested rivaroxaban regimens cut clinically significant bleeds by about 40%, compared with a warfarin-based regimen.
Data source: PIONEER AF-PCI, an international, multicenter randomized trial with 2,124 patients.
Disclosures: Dr. Gibson has received research support and consulted for Johnson & Johnson (Janssen) and Bayer, the study sponsors that also market rivaroxaban (Xarelto) worldwide, and several other drug companies.
Cardiorespiratory fitness improves survival after depression
ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.
“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.
This analysis focused on the 5,128 subjects who were on antidepressant medication at the time of their treadmill test. Their baseline cardiorespiratory fitness, as estimated by achieved peak metabolic equivalents (METs) on the treadmill, varied inversely with their risks of acute MI and all-cause mortality in the years to come. However, the less fit a patient was, the greater the burden of traditional cardiovascular risk factors. For example, the prevalence of hypertension was 86% in patients who achieved fewer than 6 METs, 75% in those who achieved 6-9 METs, 62% in depressed patients who reached 10-11 METs, and 51% in those who achieved 12 METs or more.
For this reason, Dr. Ahmed and coinvestigators performed a Cox multivariate regression analysis adjusted extensively for potential confounders, including age, sex, race, cardiovascular risk factors, known coronary artery disease, the use of cardiovascular medications, and the reason for the referral for stress testing.
When an achieved MET below 6 was used as the reference standard, for every 1 MET above 6 that patients achieved, their adjusted risk of all-cause mortality decreased by 18%, and the risk of nonfatal MI fell by 8%. 
Session cochair Martin Halle, MD, pointed out what he viewed as a major limitation of the study.
“You didn’t follow their physical fitness over time, so you can’t say that increasing their METs would bring a better prognosis,” said Dr. Halle, professor and chairman of the department of preventive and rehabilitative sports medicine at the Technical University of Munich.
Dr. Ahmed reported having no financial conflicts of interest related to the Henry Ford FIT Project.
ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.
“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.
This analysis focused on the 5,128 subjects who were on antidepressant medication at the time of their treadmill test. Their baseline cardiorespiratory fitness, as estimated by achieved peak metabolic equivalents (METs) on the treadmill, varied inversely with their risks of acute MI and all-cause mortality in the years to come. However, the less fit a patient was, the greater the burden of traditional cardiovascular risk factors. For example, the prevalence of hypertension was 86% in patients who achieved fewer than 6 METs, 75% in those who achieved 6-9 METs, 62% in depressed patients who reached 10-11 METs, and 51% in those who achieved 12 METs or more.
For this reason, Dr. Ahmed and coinvestigators performed a Cox multivariate regression analysis adjusted extensively for potential confounders, including age, sex, race, cardiovascular risk factors, known coronary artery disease, the use of cardiovascular medications, and the reason for the referral for stress testing.
When an achieved MET below 6 was used as the reference standard, for every 1 MET above 6 that patients achieved, their adjusted risk of all-cause mortality decreased by 18%, and the risk of nonfatal MI fell by 8%.
Session cochair Martin Halle, MD, pointed out what he viewed as a major limitation of the study.
“You didn’t follow their physical fitness over time, so you can’t say that increasing their METs would bring a better prognosis,” said Dr. Halle, professor and chairman of the department of preventive and rehabilitative sports medicine at the Technical University of Munich.
Dr. Ahmed reported having no financial conflicts of interest related to the Henry Ford FIT Project.
ROME – Cardiorespiratory fitness provided strong and graded protection against all-cause mortality and nonfatal MI in a study of more than 5,000 patients treated for depression, Amjad M. Ahmed, MD, reported at the annual congress of the European Society of Cardiology.
“These results highlight the importance of assessing fitness to identify risk as well as promoting an active lifestyle in patients with depression,” said Dr. Ahmed of Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia.
This analysis focused on the 5,128 subjects who were on antidepressant medication at the time of their treadmill test. Their baseline cardiorespiratory fitness, as estimated by achieved peak metabolic equivalents (METs) on the treadmill, varied inversely with their risks of acute MI and all-cause mortality in the years to come. However, the less fit a patient was, the greater the burden of traditional cardiovascular risk factors. For example, the prevalence of hypertension was 86% in patients who achieved fewer than 6 METs, 75% in those who achieved 6-9 METs, 62% in depressed patients who reached 10-11 METs, and 51% in those who achieved 12 METs or more.
For this reason, Dr. Ahmed and coinvestigators performed a Cox multivariate regression analysis adjusted extensively for potential confounders, including age, sex, race, cardiovascular risk factors, known coronary artery disease, the use of cardiovascular medications, and the reason for the referral for stress testing.
When an achieved MET below 6 was used as the reference standard, for every 1 MET above 6 that patients achieved, their adjusted risk of all-cause mortality decreased by 18%, and the risk of nonfatal MI fell by 8%.
Session cochair Martin Halle, MD, pointed out what he viewed as a major limitation of the study.
“You didn’t follow their physical fitness over time, so you can’t say that increasing their METs would bring a better prognosis,” said Dr. Halle, professor and chairman of the department of preventive and rehabilitative sports medicine at the Technical University of Munich.
Dr. Ahmed reported having no financial conflicts of interest related to the Henry Ford FIT Project.
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: For every 1-MET increase a patient on antidepressant medication achieved above 6 METs during a Bruce protocol treadmill exercise test, the risk of all-cause mortality during the subsequent 11.5 years decreased by an adjusted 18%.
Data source: A retrospective analysis of 5,128 patients on antidepressant medication who underwent a treadmill exercise test as part of the Henry Ford Exercise Testing Project and were then followed up for a median of 11.5 years.
Disclosures: The study presenter reported having no relevant financial conflicts.
Scoring formula consolidates stroke, bleeding risk in atrial fib patients
ROME – A new risk-stratification formula for atrial fibrillation patients starting oral anticoagulant therapy helps sort out their potential net benefit on edoxaban, compared with warfarin.
This risk score “could help guide selection of treatment” with a vitamin K antagonist such as warfarin or a new oral anticoagulant (NOAC) such as edoxaban, Christina L. Fanola, MD, said at the annual congress of the European Society of Cardiology.
“It’s a great time to think about this type of score, because so many more patients are being diagnosed with atrial fibrillation and there is a lot of clinical equipoise” over which anticoagulant to start patients on, said Dr. Fanola, a cardiologist at Brigham and Women’s Hospital in Boston. She said she and her associates hope to externally validate the score and test it in cohorts that received other NOACs, such as apixaban (Eliquis), dabigatran (Pradaxa), or rivaroxaban (Xarelto), but it is very possible that scoring might differ from one NOAC to the next. “Each NOAC may need its own scoring formula,” Dr. Fanola said in an interview.
A Cox proportional hazards model identified 10 demographic, clinical, and laboratory features that had significant, independent correlations to a primary outcome of disabling stroke, life-threatening bleeding, or death. After weighing the point allocation for each item by the strength of its association, the researchers developed a scoring formula in a model that could account for about 69% of the three combined adverse outcomes.
An analysis that applied the scoring formula back to the ENGAGE AF-TIMI 48 database showed that a low-risk score of 0-6 correlated with a 4% per year rate of disabling stroke, life-threatening bleed, or death; an intermediate-risk score of 7-9 correlated with a 10% per year incidence of this combined outcome, and a high-risk score of 10 or greater linked with a 21% annual event rate.
Dr. Fanola and her associates ran a further analysis that evaluated the efficacy of edoxaban, compared with warfarin, among the patients in each of these risk strata. The high-risk patients received a major benefit from edoxaban, with a 30% overall incidence of the combined endpoint during 3 years of follow-up, compared with a 51% rate among patients on warfarin, a 21-percentage-point reduction in adverse events. Intermediate-risk patients also received a significant benefit, with a 26% event rate on warfarin and an 18% rate on edoxaban. But low-risk patients had identical 10% event rates with either treatment.
These findings suggest that atrial fibrillation patients with a TIMI AF score that is high or intermediate would have a better chance for a good outcome on edoxaban, or perhaps a different NOAC, than on warfarin. Low-risk patients seem to have similar outcomes on edoxaban or warfarin, so other considerations can come into play for choosing between these drug options, such as the cost of treatment and the inconvenience of regular warfarin monitoring, Dr. Fanola said.
ENGAGE AF-TIMI 48 was sponsored by Daiichi Sankyo, the company that markets edoxaban. Dr. Fanola had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
ROME – A new risk-stratification formula for atrial fibrillation patients starting oral anticoagulant therapy helps sort out their potential net benefit on edoxaban, compared with warfarin.
This risk score “could help guide selection of treatment” with a vitamin K antagonist such as warfarin or a new oral anticoagulant (NOAC) such as edoxaban, Christina L. Fanola, MD, said at the annual congress of the European Society of Cardiology.
“It’s a great time to think about this type of score, because so many more patients are being diagnosed with atrial fibrillation and there is a lot of clinical equipoise” over which anticoagulant to start patients on, said Dr. Fanola, a cardiologist at Brigham and Women’s Hospital in Boston. She said she and her associates hope to externally validate the score and test it in cohorts that received other NOACs, such as apixaban (Eliquis), dabigatran (Pradaxa), or rivaroxaban (Xarelto), but it is very possible that scoring might differ from one NOAC to the next. “Each NOAC may need its own scoring formula,” Dr. Fanola said in an interview.
A Cox proportional hazards model identified 10 demographic, clinical, and laboratory features that had significant, independent correlations to a primary outcome of disabling stroke, life-threatening bleeding, or death. After weighing the point allocation for each item by the strength of its association, the researchers developed a scoring formula in a model that could account for about 69% of the three combined adverse outcomes.
An analysis that applied the scoring formula back to the ENGAGE AF-TIMI 48 database showed that a low-risk score of 0-6 correlated with a 4% per year rate of disabling stroke, life-threatening bleed, or death; an intermediate-risk score of 7-9 correlated with a 10% per year incidence of this combined outcome, and a high-risk score of 10 or greater linked with a 21% annual event rate.
Dr. Fanola and her associates ran a further analysis that evaluated the efficacy of edoxaban, compared with warfarin, among the patients in each of these risk strata. The high-risk patients received a major benefit from edoxaban, with a 30% overall incidence of the combined endpoint during 3 years of follow-up, compared with a 51% rate among patients on warfarin, a 21-percentage-point reduction in adverse events. Intermediate-risk patients also received a significant benefit, with a 26% event rate on warfarin and an 18% rate on edoxaban. But low-risk patients had identical 10% event rates with either treatment.
These findings suggest that atrial fibrillation patients with a TIMI AF score that is high or intermediate would have a better chance for a good outcome on edoxaban, or perhaps a different NOAC, than on warfarin. Low-risk patients seem to have similar outcomes on edoxaban or warfarin, so other considerations can come into play for choosing between these drug options, such as the cost of treatment and the inconvenience of regular warfarin monitoring, Dr. Fanola said.
ENGAGE AF-TIMI 48 was sponsored by Daiichi Sankyo, the company that markets edoxaban. Dr. Fanola had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
ROME – A new risk-stratification formula for atrial fibrillation patients starting oral anticoagulant therapy helps sort out their potential net benefit on edoxaban, compared with warfarin.
This risk score “could help guide selection of treatment” with a vitamin K antagonist such as warfarin or a new oral anticoagulant (NOAC) such as edoxaban, Christina L. Fanola, MD, said at the annual congress of the European Society of Cardiology.
“It’s a great time to think about this type of score, because so many more patients are being diagnosed with atrial fibrillation and there is a lot of clinical equipoise” over which anticoagulant to start patients on, said Dr. Fanola, a cardiologist at Brigham and Women’s Hospital in Boston. She said she and her associates hope to externally validate the score and test it in cohorts that received other NOACs, such as apixaban (Eliquis), dabigatran (Pradaxa), or rivaroxaban (Xarelto), but it is very possible that scoring might differ from one NOAC to the next. “Each NOAC may need its own scoring formula,” Dr. Fanola said in an interview.
A Cox proportional hazards model identified 10 demographic, clinical, and laboratory features that had significant, independent correlations to a primary outcome of disabling stroke, life-threatening bleeding, or death. After weighing the point allocation for each item by the strength of its association, the researchers developed a scoring formula in a model that could account for about 69% of the three combined adverse outcomes.
An analysis that applied the scoring formula back to the ENGAGE AF-TIMI 48 database showed that a low-risk score of 0-6 correlated with a 4% per year rate of disabling stroke, life-threatening bleed, or death; an intermediate-risk score of 7-9 correlated with a 10% per year incidence of this combined outcome, and a high-risk score of 10 or greater linked with a 21% annual event rate.
Dr. Fanola and her associates ran a further analysis that evaluated the efficacy of edoxaban, compared with warfarin, among the patients in each of these risk strata. The high-risk patients received a major benefit from edoxaban, with a 30% overall incidence of the combined endpoint during 3 years of follow-up, compared with a 51% rate among patients on warfarin, a 21-percentage-point reduction in adverse events. Intermediate-risk patients also received a significant benefit, with a 26% event rate on warfarin and an 18% rate on edoxaban. But low-risk patients had identical 10% event rates with either treatment.
These findings suggest that atrial fibrillation patients with a TIMI AF score that is high or intermediate would have a better chance for a good outcome on edoxaban, or perhaps a different NOAC, than on warfarin. Low-risk patients seem to have similar outcomes on edoxaban or warfarin, so other considerations can come into play for choosing between these drug options, such as the cost of treatment and the inconvenience of regular warfarin monitoring, Dr. Fanola said.
ENGAGE AF-TIMI 48 was sponsored by Daiichi Sankyo, the company that markets edoxaban. Dr. Fanola had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: Among high-risk patients, edoxaban cut adverse events by 21 percentage points, compared with warfarin.
Data source: ENGAGE AF-TIMI 48, a multicenter trial with 21,105 patients.
Disclosures: ENGAGE AF-TIMI 48 was sponsored by Daiichi Sankyo, the company that markets edoxaban (Savaysa). Dr. Fanola had no relevant financial disclosures.
ReACT: No benefit from routine coronary angiography after PCI
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).
Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).
In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).
Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)
The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.
“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.
Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.
In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.
“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.
“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”
Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.
While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.
“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”
This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Key clinical point: Routine follow-up coronary angiography after percutaneous coronary intervention increases rates of coronary revascularization but does not improve outcomes.
Major finding: Patients who underwent routine angiographic follow-up had a similar cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure as those who had standard clinical follow-up.
Data source: ReACT: a prospective, open-label randomized controlled trial in 700 patients after percutaneous coronary intervention.
Disclosures: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
Interrupting oral anticoagulation in AF carries high thromboembolic cost
ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.
The ENGAGE-AF TIMI 48 study was the pivotal phase III, double-blind, 21,105-patient clinical trial that led to Food and Drug Administration and European approval of the direct oral factor Xa inhibitor edoxaban (Savaysa) for stroke prevention in moderate- to high-risk patients with AF (N Engl J Med. 2013 Nov 28;369[22]:2093-104). The study showed that edoxaban at what later became the approved dose of 60 mg/day, or 30 mg/day in patients with impaired renal function, body weight of 60 kg or less, or on concomitant therapy with a platelet glycoprotein inhibitor, resulted in a 21% reduction in the risk of stroke or systemic embolism and a 20% reduction in major bleeding, compared with warfarin over 2.8 years of follow-up.
Dr. Cavallari presented a prespecified secondary retrospective analysis that focused on treatment interruptions: the reasons and the price paid in terms of thromboembolic events.
One or more treatment interruptions lasting for longer than 3 days occurred in 63% of patients during a median 2.8 years of follow-up. Since these were participants in a clinical trial with relatively close patient contact, it’s likely that the true interruption rate in real-world clinical practice is even higher, she said.
Interruptions were more significantly frequent in patients assigned to warfarin than among the groups assigned to edoxaban. The median duration of treatment interruptions was 9 days.
After excluding patients who were on any other anticoagulant during their interruption – low-molecular-weight heparin being the most common – investigators were left with 9,148 patients.
The endpoints of interest in this analysis were the major adverse events occurring during a time window lasting from 4 days after their last dose of oral anticoagulant until day 34 or when they resumed their study drug. The 30-day incidence of ischemic stroke or systemic embolism was 1.27%. The rate of a composite composed of cardiovascular death, MI, and ischemic stroke or systemic embolism was 4.99%. And the 30-day rate of an endpoint Dr. Cavallari termed primary net clinical outcome – a composite of stroke or systemic embolism, major bleeding, and all-cause mortality – was 7.16%.
These 30-day event rates among treatment interrupters are extremely high, compared with the 1-year rates in patients who didn’t interrupt oral anticoagulant therapy: 0.26% for ischemic stroke or systemic embolism; 0.36% for the composite of cardiovascular death, MI, and ischemic stroke; and 0.56% for the primary net clinical outcome, she continued.
The most common reason for treatment interruptions was adverse events, which accounted for 41% of the interruptions.
Drilling deeper into the types of adverse events that triggered treatment interruption, 1.5% of interrupters did so because of an on-treatment ischemic stroke or systemic embolism, 4.7% did so because of major bleeding, 8% had minor and clinically relevant nonmajor bleeding, another 30% interrupted treatment for other serious or nonserious adverse events.
Interrupting therapy because of an adverse event often had serious consequences, as reflected in an adjusted 3.94-fold increased risk of 30-day all-cause mortality, compared with patients who stopped for other reasons. Patients who stopped treatment because of a stroke, transient ischemic attack, or systemic embolism had a 30-day all-cause mortality of 29.3%. Those who interrupted treatment because of a major bleeding event had an 8.8% 30-day mortality. When minor or clinically relevant nonmajor bleeding was the impetus for a treatment interruption, the associated 30-day mortality was 3.4%.
Almost a third (29%) of treatment interruptions were the result of physician decisions in response to an upcoming invasive procedure, most often dental work.
The 30-day rates of ischemic stroke/systemic embolism and primary net clinical outcome didn’t differ significantly between patients who interrupted warfarin versus edoxaban at the approved dose. Nonetheless, this new secondary analysis from ENGAGE-AF TIMI 48 supports the parent study’s conclusion that edoxaban is preferable to warfarin in patients with AF, according to Dr. Cavallari.
“In light of the increased risk of ischemic events after interruption of oral anticoagulation, NOACs [new oral anticoagulants] represent an attractive alternative to vitamin K antagonists, given their faster onset of action, better adherence rates, safety, and tolerability profiles,” she concluded.
ENGAGE AF-TIMI 48 was funded by Daiichi Sankyo. Dr. Cavallari reported having no financial conflicts of interest regarding her presentation.
ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.
The ENGAGE-AF TIMI 48 study was the pivotal phase III, double-blind, 21,105-patient clinical trial that led to Food and Drug Administration and European approval of the direct oral factor Xa inhibitor edoxaban (Savaysa) for stroke prevention in moderate- to high-risk patients with AF (N Engl J Med. 2013 Nov 28;369[22]:2093-104). The study showed that edoxaban at what later became the approved dose of 60 mg/day, or 30 mg/day in patients with impaired renal function, body weight of 60 kg or less, or on concomitant therapy with a platelet glycoprotein inhibitor, resulted in a 21% reduction in the risk of stroke or systemic embolism and a 20% reduction in major bleeding, compared with warfarin over 2.8 years of follow-up.
Dr. Cavallari presented a prespecified secondary retrospective analysis that focused on treatment interruptions: the reasons and the price paid in terms of thromboembolic events.
One or more treatment interruptions lasting for longer than 3 days occurred in 63% of patients during a median 2.8 years of follow-up. Since these were participants in a clinical trial with relatively close patient contact, it’s likely that the true interruption rate in real-world clinical practice is even higher, she said.
Interruptions were more significantly frequent in patients assigned to warfarin than among the groups assigned to edoxaban. The median duration of treatment interruptions was 9 days.
After excluding patients who were on any other anticoagulant during their interruption – low-molecular-weight heparin being the most common – investigators were left with 9,148 patients.
The endpoints of interest in this analysis were the major adverse events occurring during a time window lasting from 4 days after their last dose of oral anticoagulant until day 34 or when they resumed their study drug. The 30-day incidence of ischemic stroke or systemic embolism was 1.27%. The rate of a composite composed of cardiovascular death, MI, and ischemic stroke or systemic embolism was 4.99%. And the 30-day rate of an endpoint Dr. Cavallari termed primary net clinical outcome – a composite of stroke or systemic embolism, major bleeding, and all-cause mortality – was 7.16%.
These 30-day event rates among treatment interrupters are extremely high, compared with the 1-year rates in patients who didn’t interrupt oral anticoagulant therapy: 0.26% for ischemic stroke or systemic embolism; 0.36% for the composite of cardiovascular death, MI, and ischemic stroke; and 0.56% for the primary net clinical outcome, she continued.
The most common reason for treatment interruptions was adverse events, which accounted for 41% of the interruptions.
Drilling deeper into the types of adverse events that triggered treatment interruption, 1.5% of interrupters did so because of an on-treatment ischemic stroke or systemic embolism, 4.7% did so because of major bleeding, 8% had minor and clinically relevant nonmajor bleeding, another 30% interrupted treatment for other serious or nonserious adverse events.
Interrupting therapy because of an adverse event often had serious consequences, as reflected in an adjusted 3.94-fold increased risk of 30-day all-cause mortality, compared with patients who stopped for other reasons. Patients who stopped treatment because of a stroke, transient ischemic attack, or systemic embolism had a 30-day all-cause mortality of 29.3%. Those who interrupted treatment because of a major bleeding event had an 8.8% 30-day mortality. When minor or clinically relevant nonmajor bleeding was the impetus for a treatment interruption, the associated 30-day mortality was 3.4%.
Almost a third (29%) of treatment interruptions were the result of physician decisions in response to an upcoming invasive procedure, most often dental work.
The 30-day rates of ischemic stroke/systemic embolism and primary net clinical outcome didn’t differ significantly between patients who interrupted warfarin versus edoxaban at the approved dose. Nonetheless, this new secondary analysis from ENGAGE-AF TIMI 48 supports the parent study’s conclusion that edoxaban is preferable to warfarin in patients with AF, according to Dr. Cavallari.
“In light of the increased risk of ischemic events after interruption of oral anticoagulation, NOACs [new oral anticoagulants] represent an attractive alternative to vitamin K antagonists, given their faster onset of action, better adherence rates, safety, and tolerability profiles,” she concluded.
ENGAGE AF-TIMI 48 was funded by Daiichi Sankyo. Dr. Cavallari reported having no financial conflicts of interest regarding her presentation.
ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.
The ENGAGE-AF TIMI 48 study was the pivotal phase III, double-blind, 21,105-patient clinical trial that led to Food and Drug Administration and European approval of the direct oral factor Xa inhibitor edoxaban (Savaysa) for stroke prevention in moderate- to high-risk patients with AF (N Engl J Med. 2013 Nov 28;369[22]:2093-104). The study showed that edoxaban at what later became the approved dose of 60 mg/day, or 30 mg/day in patients with impaired renal function, body weight of 60 kg or less, or on concomitant therapy with a platelet glycoprotein inhibitor, resulted in a 21% reduction in the risk of stroke or systemic embolism and a 20% reduction in major bleeding, compared with warfarin over 2.8 years of follow-up.
Dr. Cavallari presented a prespecified secondary retrospective analysis that focused on treatment interruptions: the reasons and the price paid in terms of thromboembolic events.
One or more treatment interruptions lasting for longer than 3 days occurred in 63% of patients during a median 2.8 years of follow-up. Since these were participants in a clinical trial with relatively close patient contact, it’s likely that the true interruption rate in real-world clinical practice is even higher, she said.
Interruptions were more significantly frequent in patients assigned to warfarin than among the groups assigned to edoxaban. The median duration of treatment interruptions was 9 days.
After excluding patients who were on any other anticoagulant during their interruption – low-molecular-weight heparin being the most common – investigators were left with 9,148 patients.
The endpoints of interest in this analysis were the major adverse events occurring during a time window lasting from 4 days after their last dose of oral anticoagulant until day 34 or when they resumed their study drug. The 30-day incidence of ischemic stroke or systemic embolism was 1.27%. The rate of a composite composed of cardiovascular death, MI, and ischemic stroke or systemic embolism was 4.99%. And the 30-day rate of an endpoint Dr. Cavallari termed primary net clinical outcome – a composite of stroke or systemic embolism, major bleeding, and all-cause mortality – was 7.16%.
These 30-day event rates among treatment interrupters are extremely high, compared with the 1-year rates in patients who didn’t interrupt oral anticoagulant therapy: 0.26% for ischemic stroke or systemic embolism; 0.36% for the composite of cardiovascular death, MI, and ischemic stroke; and 0.56% for the primary net clinical outcome, she continued.
The most common reason for treatment interruptions was adverse events, which accounted for 41% of the interruptions.
Drilling deeper into the types of adverse events that triggered treatment interruption, 1.5% of interrupters did so because of an on-treatment ischemic stroke or systemic embolism, 4.7% did so because of major bleeding, 8% had minor and clinically relevant nonmajor bleeding, another 30% interrupted treatment for other serious or nonserious adverse events.
Interrupting therapy because of an adverse event often had serious consequences, as reflected in an adjusted 3.94-fold increased risk of 30-day all-cause mortality, compared with patients who stopped for other reasons. Patients who stopped treatment because of a stroke, transient ischemic attack, or systemic embolism had a 30-day all-cause mortality of 29.3%. Those who interrupted treatment because of a major bleeding event had an 8.8% 30-day mortality. When minor or clinically relevant nonmajor bleeding was the impetus for a treatment interruption, the associated 30-day mortality was 3.4%.
Almost a third (29%) of treatment interruptions were the result of physician decisions in response to an upcoming invasive procedure, most often dental work.
The 30-day rates of ischemic stroke/systemic embolism and primary net clinical outcome didn’t differ significantly between patients who interrupted warfarin versus edoxaban at the approved dose. Nonetheless, this new secondary analysis from ENGAGE-AF TIMI 48 supports the parent study’s conclusion that edoxaban is preferable to warfarin in patients with AF, according to Dr. Cavallari.
“In light of the increased risk of ischemic events after interruption of oral anticoagulation, NOACs [new oral anticoagulants] represent an attractive alternative to vitamin K antagonists, given their faster onset of action, better adherence rates, safety, and tolerability profiles,” she concluded.
ENGAGE AF-TIMI 48 was funded by Daiichi Sankyo. Dr. Cavallari reported having no financial conflicts of interest regarding her presentation.
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: Atrial fibrillation patients who interrupted oral anticoagulation with edoxaban or warfarin for stroke prevention for longer than 3 days had a 127-fold increase in 30-day risk of the composite of stroke or systemic embolism, major bleeding, or all-cause mortality, compared with patients who didn’t interrupt treatment after 1 year.
Data source: A prespecified secondary analysis of 9,148 patients with atrial fibrillation who interrupted oral anticoagulation therapy with warfarin or edoxaban for longer than 3 days during a median follow-up of 2.8 years in the phase III, randomized, double-blind ENGAGE AF-TIMI 48 trial, and the consequences thereof.
Disclosures: The ENGAGE AF-TIMI 48 trial was funded by Daiichi Sankyo, which markets edoxaban. However, the presenter of this secondary analysis reported having no relevant financial interests.
Adaptive servo ventilation cuts atrial fib burden
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
[email protected]
On Twitter @mitchelzoler
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
[email protected]
On Twitter @mitchelzoler
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
[email protected]
On Twitter @mitchelzoler
Key clinical point:
Major finding: After 6 months, ASV produced a relative 21% drop in atrial fibrillation burden, compared with increased burden in control patients.
Data source: CAT-HF, a multicenter randomized trial that enrolled 126 heart failure patients with sleep apnea.
Disclosures: The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support and/or consultant fees from ResMed, Janssen, Gilead, St. Jude, Spectranetics, Medtronic, GSK and BMS-Pfizer.