Anticoagulation Hub

TORONTO – The risk of recurrence following an initial episode of venous thromboembolism is highest in the first 3 months, but remains high for up to 3 years, according to findings from a population-based study involving 2,989 adults.

Over a mean of 23 months (median, 30 months), there were 329 VTE recurrences in the study subjects. Cumulative incidence rates were 5.1% at 3 months, and 14.5% at 3 years. The corresponding rates were 8.7% and 24.8% among those with active cancer, 5.2% and 13.0% among those with provoked VTE, and 3.8% and 13.1% among those with unprovoked VTE, Dr. Wei Huang reported at the International Society on Thrombosis and Haemostasis congress.

Courtesy Yale Rosen/Wikimedia Commons

Independent predictors of recurrence within 3 years after the index event were active cancer with chemotherapy (hazard ratio, 2.59), active cancer without chemotherapy (HR, 1.59), hypercoagulable state (HR, 2.53) superficial thrombophlebitis (HR, 1.62), varicose vein stripping (HR, 1.75), and inferior vena cava (IVC) filter placement (HR, 2.04), said Dr. Huang of the University of Massachusetts, Worcester.

Individuals included in the study were all residents of the Worcester Metropolitan Statistical Area (WMSA) who had a validated diagnosis of acute first-time deep vein thrombosis and/or pulmonary embolism in a hospital or ambulatory care center that provided short-term care for WMSA residents between 1999 and 2009. Medical records and national and local death registry data were reviewed to examine outcomes up to 3 years after the index event.

Subjects were adults with a mean age of 64 years; 44% were men, and 94% where white. Pulmonary embolism with or without deep vein thrombosis occurred in 42%, and 17% of cases were associated with cancer, 43% involved provoked VTE, and 40% involved unprovoked VTE.

Provoked VTE was defined as VTE occurring within 3 months of a prior surgery, pregnancy, trauma, fracture, or hospitalization in patients without presence of active cancer.

Though limited by the lack of information about variations in physician practices across regions, and by the high proportion of white resident in the WMSA, which both raise questions about whether the findings are generalizable to the U.S. population, the identification of these predictors could allow for improved estimation of risk for individual patients, and may aid in the design of new interventional studies, Dr. Huang concluded.

This study was supported by the National Institutes of Health.

sworcester@frontlinemedcom.com

TORONTO – The risk of recurrence following an initial episode of venous thromboembolism is highest in the first 3 months, but remains high for up to 3 years, according to findings from a population-based study involving 2,989 adults.

Over a mean of 23 months (median, 30 months), there were 329 VTE recurrences in the study subjects. Cumulative incidence rates were 5.1% at 3 months, and 14.5% at 3 years. The corresponding rates were 8.7% and 24.8% among those with active cancer, 5.2% and 13.0% among those with provoked VTE, and 3.8% and 13.1% among those with unprovoked VTE, Dr. Wei Huang reported at the International Society on Thrombosis and Haemostasis congress.

Courtesy Yale Rosen/Wikimedia Commons

Independent predictors of recurrence within 3 years after the index event were active cancer with chemotherapy (hazard ratio, 2.59), active cancer without chemotherapy (HR, 1.59), hypercoagulable state (HR, 2.53) superficial thrombophlebitis (HR, 1.62), varicose vein stripping (HR, 1.75), and inferior vena cava (IVC) filter placement (HR, 2.04), said Dr. Huang of the University of Massachusetts, Worcester.

Individuals included in the study were all residents of the Worcester Metropolitan Statistical Area (WMSA) who had a validated diagnosis of acute first-time deep vein thrombosis and/or pulmonary embolism in a hospital or ambulatory care center that provided short-term care for WMSA residents between 1999 and 2009. Medical records and national and local death registry data were reviewed to examine outcomes up to 3 years after the index event.

Subjects were adults with a mean age of 64 years; 44% were men, and 94% where white. Pulmonary embolism with or without deep vein thrombosis occurred in 42%, and 17% of cases were associated with cancer, 43% involved provoked VTE, and 40% involved unprovoked VTE.

Provoked VTE was defined as VTE occurring within 3 months of a prior surgery, pregnancy, trauma, fracture, or hospitalization in patients without presence of active cancer.

Though limited by the lack of information about variations in physician practices across regions, and by the high proportion of white resident in the WMSA, which both raise questions about whether the findings are generalizable to the U.S. population, the identification of these predictors could allow for improved estimation of risk for individual patients, and may aid in the design of new interventional studies, Dr. Huang concluded.

This study was supported by the National Institutes of Health.

sworcester@frontlinemedcom.com

TORONTO – The risk of recurrence following an initial episode of venous thromboembolism is highest in the first 3 months, but remains high for up to 3 years, according to findings from a population-based study involving 2,989 adults.

Over a mean of 23 months (median, 30 months), there were 329 VTE recurrences in the study subjects. Cumulative incidence rates were 5.1% at 3 months, and 14.5% at 3 years. The corresponding rates were 8.7% and 24.8% among those with active cancer, 5.2% and 13.0% among those with provoked VTE, and 3.8% and 13.1% among those with unprovoked VTE, Dr. Wei Huang reported at the International Society on Thrombosis and Haemostasis congress.

Courtesy Yale Rosen/Wikimedia Commons

Independent predictors of recurrence within 3 years after the index event were active cancer with chemotherapy (hazard ratio, 2.59), active cancer without chemotherapy (HR, 1.59), hypercoagulable state (HR, 2.53) superficial thrombophlebitis (HR, 1.62), varicose vein stripping (HR, 1.75), and inferior vena cava (IVC) filter placement (HR, 2.04), said Dr. Huang of the University of Massachusetts, Worcester.

Individuals included in the study were all residents of the Worcester Metropolitan Statistical Area (WMSA) who had a validated diagnosis of acute first-time deep vein thrombosis and/or pulmonary embolism in a hospital or ambulatory care center that provided short-term care for WMSA residents between 1999 and 2009. Medical records and national and local death registry data were reviewed to examine outcomes up to 3 years after the index event.

Subjects were adults with a mean age of 64 years; 44% were men, and 94% where white. Pulmonary embolism with or without deep vein thrombosis occurred in 42%, and 17% of cases were associated with cancer, 43% involved provoked VTE, and 40% involved unprovoked VTE.

Provoked VTE was defined as VTE occurring within 3 months of a prior surgery, pregnancy, trauma, fracture, or hospitalization in patients without presence of active cancer.

Though limited by the lack of information about variations in physician practices across regions, and by the high proportion of white resident in the WMSA, which both raise questions about whether the findings are generalizable to the U.S. population, the identification of these predictors could allow for improved estimation of risk for individual patients, and may aid in the design of new interventional studies, Dr. Huang concluded.

This study was supported by the National Institutes of Health.

sworcester@frontlinemedcom.com

TORONTO – The use of statins showed no benefit in reducing the risk of recurrent venous thromboembolism in patients enrolled in phase III trials comparing direct oral anticoagulants with vitamin K antagonists, a large meta-analysis demonstrated.

Recurrence after an unprovoked VTE is 10%-15% in the first 6-12 months, and recurrence risk in the first 6 months is reduced by 80%-90% with anticoagulants, Dr. Mandy N. Lauw said at the International Society on Thrombosis and Haemostasis congress.

“However, the use of anticoagulants has the risk of bleeding, and therefore the long-term risk-benefit ratio is unclear,” said Dr. Lauw of the department of vascular medicine at Academic Medical Center, Amsterdam. “Therefore it’s interesting to look at modalities outside the coagulation cascade to treat patients for longer term and to prevent recurrent thrombosis. One of these modalities has been the use of statins, which are known to reduce arterial vascular events by lowering cholesterol levels. However, recent studies have also indicated that they may have an effect on VTE events.”

In an effort to evaluate the effects of statins on recurrent VTE, Dr. Lauw and her associates conducted a meta-analysis of statins in three randomized, phase III trials comparing non–vitamin K oral anticoagulant (NOAC) with vitamin K antagonist (VKA) therapy in patients with acute symptomatic VTE.

The trials included 5,153 patients enrolled in RE-COVER I and II (an analysis of dabigatran vs. standard therapy for acute VTE), 8,281 enrolled in the EINSTEIN clinical trials for DVT and pulmonary embolism (an analysis of rivaroxaban vs. standard therapy for symptomatic VTE), and 8,292 enrolled in a trial conducted by the Hokusai-DVT investigators (an analysis of edoxaban vs. standard therapy for symptomatic VTE). The researchers examined the effect of statin use on recurrent VTE or VTE-related death, recurrent DVT or PE, and major bleeding. To do this they conducted a pooled meta-analysis and an analysis per study, adjusted for age, gender, diabetes mellitus, creatinine clearance of less than 50 mL/min, hypertension, prior VTE, and use of aspirin.

Dr. Lauw reported results from 21,587 patients included in the analysis. Among all three studies, 2,754 patients (12.8%) used statins and 18,833 (87.2%) did not. In an unadjusted pooled analysis, the use of statins at baseline did not have an influence on the risk of recurrent VTE or VTE-related death, with an odds ratio of 0.91. There was also no effect of statins on the risk of recurrent PE or DVT (ORs of 0.84 and 1.05, respectively), while major bleeding seemed to be increased with the use of statins (OR, 1.65). A subanalysis in patients getting NOAC or VKA separately showed a non–statistically significant benefit of statins with NOACs, compared with VKAs on the risk of recurrent VTE or VTE-related death (ORs of 0.60 vs. OR 1.24, respectively). The results were similar for NOACs, compared with VKA, on the risk of recurrent DVT (ORs of 0.47 vs. OR 1.67) and the risk of recurrent PE (ORs of 0.73 vs. 1.02).

On adjusted analysis, the risk of recurrent VTE or VTE-related death between all three studies was similar and nonsignificant (hazard ratio of 0.99 in RE-COVER I and II, HR of 0.78 in the EINSTEIN clinical trials for DVT & PE, and HR of 0.99 in the trial conducted by the Hokusai-DVT Investigators). There also were no significant differences between the study groups in recurrent PE, recurrent DVT, or major bleeding. “So statins have no beneficial effect, but also no harmful effect,” Dr. Lauw said.

She acknowledged certain limitations of the study, including the fact that it was an on-treatment analysis, “so it could be that we had inadequate follow-up duration,” she said. “Also, we don’t have any assessment of statin effects without anticoagulation in these patients. Perhaps it would be interesting to use the extension trials to explore these results as well.”

For now, “there is no evidence that statins reduce the recurrence of VTE,” she concluded. “The only way to explore this is to do a randomized controlled trial properly designed and powered to estimate this effect prospectively.”

Dr. Lauw reported having no financial disclosures.

dbrunk@frontlinemedcom.com

TORONTO – The use of statins showed no benefit in reducing the risk of recurrent venous thromboembolism in patients enrolled in phase III trials comparing direct oral anticoagulants with vitamin K antagonists, a large meta-analysis demonstrated.

Recurrence after an unprovoked VTE is 10%-15% in the first 6-12 months, and recurrence risk in the first 6 months is reduced by 80%-90% with anticoagulants, Dr. Mandy N. Lauw said at the International Society on Thrombosis and Haemostasis congress.

“However, the use of anticoagulants has the risk of bleeding, and therefore the long-term risk-benefit ratio is unclear,” said Dr. Lauw of the department of vascular medicine at Academic Medical Center, Amsterdam. “Therefore it’s interesting to look at modalities outside the coagulation cascade to treat patients for longer term and to prevent recurrent thrombosis. One of these modalities has been the use of statins, which are known to reduce arterial vascular events by lowering cholesterol levels. However, recent studies have also indicated that they may have an effect on VTE events.”

In an effort to evaluate the effects of statins on recurrent VTE, Dr. Lauw and her associates conducted a meta-analysis of statins in three randomized, phase III trials comparing non–vitamin K oral anticoagulant (NOAC) with vitamin K antagonist (VKA) therapy in patients with acute symptomatic VTE.

The trials included 5,153 patients enrolled in RE-COVER I and II (an analysis of dabigatran vs. standard therapy for acute VTE), 8,281 enrolled in the EINSTEIN clinical trials for DVT and pulmonary embolism (an analysis of rivaroxaban vs. standard therapy for symptomatic VTE), and 8,292 enrolled in a trial conducted by the Hokusai-DVT investigators (an analysis of edoxaban vs. standard therapy for symptomatic VTE). The researchers examined the effect of statin use on recurrent VTE or VTE-related death, recurrent DVT or PE, and major bleeding. To do this they conducted a pooled meta-analysis and an analysis per study, adjusted for age, gender, diabetes mellitus, creatinine clearance of less than 50 mL/min, hypertension, prior VTE, and use of aspirin.

Dr. Lauw reported results from 21,587 patients included in the analysis. Among all three studies, 2,754 patients (12.8%) used statins and 18,833 (87.2%) did not. In an unadjusted pooled analysis, the use of statins at baseline did not have an influence on the risk of recurrent VTE or VTE-related death, with an odds ratio of 0.91. There was also no effect of statins on the risk of recurrent PE or DVT (ORs of 0.84 and 1.05, respectively), while major bleeding seemed to be increased with the use of statins (OR, 1.65). A subanalysis in patients getting NOAC or VKA separately showed a non–statistically significant benefit of statins with NOACs, compared with VKAs on the risk of recurrent VTE or VTE-related death (ORs of 0.60 vs. OR 1.24, respectively). The results were similar for NOACs, compared with VKA, on the risk of recurrent DVT (ORs of 0.47 vs. OR 1.67) and the risk of recurrent PE (ORs of 0.73 vs. 1.02).

On adjusted analysis, the risk of recurrent VTE or VTE-related death between all three studies was similar and nonsignificant (hazard ratio of 0.99 in RE-COVER I and II, HR of 0.78 in the EINSTEIN clinical trials for DVT & PE, and HR of 0.99 in the trial conducted by the Hokusai-DVT Investigators). There also were no significant differences between the study groups in recurrent PE, recurrent DVT, or major bleeding. “So statins have no beneficial effect, but also no harmful effect,” Dr. Lauw said.

She acknowledged certain limitations of the study, including the fact that it was an on-treatment analysis, “so it could be that we had inadequate follow-up duration,” she said. “Also, we don’t have any assessment of statin effects without anticoagulation in these patients. Perhaps it would be interesting to use the extension trials to explore these results as well.”

For now, “there is no evidence that statins reduce the recurrence of VTE,” she concluded. “The only way to explore this is to do a randomized controlled trial properly designed and powered to estimate this effect prospectively.”

Dr. Lauw reported having no financial disclosures.

dbrunk@frontlinemedcom.com

TORONTO – The use of statins showed no benefit in reducing the risk of recurrent venous thromboembolism in patients enrolled in phase III trials comparing direct oral anticoagulants with vitamin K antagonists, a large meta-analysis demonstrated.

Recurrence after an unprovoked VTE is 10%-15% in the first 6-12 months, and recurrence risk in the first 6 months is reduced by 80%-90% with anticoagulants, Dr. Mandy N. Lauw said at the International Society on Thrombosis and Haemostasis congress.

“However, the use of anticoagulants has the risk of bleeding, and therefore the long-term risk-benefit ratio is unclear,” said Dr. Lauw of the department of vascular medicine at Academic Medical Center, Amsterdam. “Therefore it’s interesting to look at modalities outside the coagulation cascade to treat patients for longer term and to prevent recurrent thrombosis. One of these modalities has been the use of statins, which are known to reduce arterial vascular events by lowering cholesterol levels. However, recent studies have also indicated that they may have an effect on VTE events.”

In an effort to evaluate the effects of statins on recurrent VTE, Dr. Lauw and her associates conducted a meta-analysis of statins in three randomized, phase III trials comparing non–vitamin K oral anticoagulant (NOAC) with vitamin K antagonist (VKA) therapy in patients with acute symptomatic VTE.

The trials included 5,153 patients enrolled in RE-COVER I and II (an analysis of dabigatran vs. standard therapy for acute VTE), 8,281 enrolled in the EINSTEIN clinical trials for DVT and pulmonary embolism (an analysis of rivaroxaban vs. standard therapy for symptomatic VTE), and 8,292 enrolled in a trial conducted by the Hokusai-DVT investigators (an analysis of edoxaban vs. standard therapy for symptomatic VTE). The researchers examined the effect of statin use on recurrent VTE or VTE-related death, recurrent DVT or PE, and major bleeding. To do this they conducted a pooled meta-analysis and an analysis per study, adjusted for age, gender, diabetes mellitus, creatinine clearance of less than 50 mL/min, hypertension, prior VTE, and use of aspirin.

Dr. Lauw reported results from 21,587 patients included in the analysis. Among all three studies, 2,754 patients (12.8%) used statins and 18,833 (87.2%) did not. In an unadjusted pooled analysis, the use of statins at baseline did not have an influence on the risk of recurrent VTE or VTE-related death, with an odds ratio of 0.91. There was also no effect of statins on the risk of recurrent PE or DVT (ORs of 0.84 and 1.05, respectively), while major bleeding seemed to be increased with the use of statins (OR, 1.65). A subanalysis in patients getting NOAC or VKA separately showed a non–statistically significant benefit of statins with NOACs, compared with VKAs on the risk of recurrent VTE or VTE-related death (ORs of 0.60 vs. OR 1.24, respectively). The results were similar for NOACs, compared with VKA, on the risk of recurrent DVT (ORs of 0.47 vs. OR 1.67) and the risk of recurrent PE (ORs of 0.73 vs. 1.02).

On adjusted analysis, the risk of recurrent VTE or VTE-related death between all three studies was similar and nonsignificant (hazard ratio of 0.99 in RE-COVER I and II, HR of 0.78 in the EINSTEIN clinical trials for DVT & PE, and HR of 0.99 in the trial conducted by the Hokusai-DVT Investigators). There also were no significant differences between the study groups in recurrent PE, recurrent DVT, or major bleeding. “So statins have no beneficial effect, but also no harmful effect,” Dr. Lauw said.

She acknowledged certain limitations of the study, including the fact that it was an on-treatment analysis, “so it could be that we had inadequate follow-up duration,” she said. “Also, we don’t have any assessment of statin effects without anticoagulation in these patients. Perhaps it would be interesting to use the extension trials to explore these results as well.”

For now, “there is no evidence that statins reduce the recurrence of VTE,” she concluded. “The only way to explore this is to do a randomized controlled trial properly designed and powered to estimate this effect prospectively.”

Dr. Lauw reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Though acute coronary syndromes are the leading cause of death in U.S. women, an analysis of clinical trials showed that enrollment among women remained disproportionately low from 1994 to 2010, reported Dr. Kristian Kragholm and coauthors at Duke Clinical Research Institute.

An analysis of data in 76,148 non–ST-segment elevation acute coronary syndrome patients from 11 phase III clinical trials found that women comprised just 33.3% of participants, which did not change significantly over the 17-year period. Women consistently had higher incidence of diabetes, hypertension, and heart failure, the authors reported.

Use of ACE inhibitors/angiotensin II receptor blockers, thienopyridines, beta-blockers, and lipid-lowering drugs significantly increased over time for both sexes, as did use of coronary angiography and percutaneous coronary intervention. Observed in-hospital, 30-day, and 6-month mortality decreased significantly in both men and women, Dr. Kragholm and colleagues said.

The findings suggest that “current efforts to representatively enroll women in NSTE ACS trials are insufficient,” the authors wrote. “Because safety and efficacy findings may differ according to sex, this disparity could undermine generalizability of clinical trial results to treatment of the overall NSTE ACS population.”

Read the full article here.

Though acute coronary syndromes are the leading cause of death in U.S. women, an analysis of clinical trials showed that enrollment among women remained disproportionately low from 1994 to 2010, reported Dr. Kristian Kragholm and coauthors at Duke Clinical Research Institute.

An analysis of data in 76,148 non–ST-segment elevation acute coronary syndrome patients from 11 phase III clinical trials found that women comprised just 33.3% of participants, which did not change significantly over the 17-year period. Women consistently had higher incidence of diabetes, hypertension, and heart failure, the authors reported.

Use of ACE inhibitors/angiotensin II receptor blockers, thienopyridines, beta-blockers, and lipid-lowering drugs significantly increased over time for both sexes, as did use of coronary angiography and percutaneous coronary intervention. Observed in-hospital, 30-day, and 6-month mortality decreased significantly in both men and women, Dr. Kragholm and colleagues said.

The findings suggest that “current efforts to representatively enroll women in NSTE ACS trials are insufficient,” the authors wrote. “Because safety and efficacy findings may differ according to sex, this disparity could undermine generalizability of clinical trial results to treatment of the overall NSTE ACS population.”

Read the full article here.

Though acute coronary syndromes are the leading cause of death in U.S. women, an analysis of clinical trials showed that enrollment among women remained disproportionately low from 1994 to 2010, reported Dr. Kristian Kragholm and coauthors at Duke Clinical Research Institute.

An analysis of data in 76,148 non–ST-segment elevation acute coronary syndrome patients from 11 phase III clinical trials found that women comprised just 33.3% of participants, which did not change significantly over the 17-year period. Women consistently had higher incidence of diabetes, hypertension, and heart failure, the authors reported.

Use of ACE inhibitors/angiotensin II receptor blockers, thienopyridines, beta-blockers, and lipid-lowering drugs significantly increased over time for both sexes, as did use of coronary angiography and percutaneous coronary intervention. Observed in-hospital, 30-day, and 6-month mortality decreased significantly in both men and women, Dr. Kragholm and colleagues said.

The findings suggest that “current efforts to representatively enroll women in NSTE ACS trials are insufficient,” the authors wrote. “Because safety and efficacy findings may differ according to sex, this disparity could undermine generalizability of clinical trial results to treatment of the overall NSTE ACS population.”

Read the full article here.

Adding an extra 18 months of warfarin therapy to the standard 6 months of anticoagulation delays the recurrence of venous thrombosis in patients who have a first episode of unprovoked pulmonary embolism – but the risk of recurrence resumes as soon as the warfarin is discontinued, according to a report published online July 7 in JAMA.

“Our results suggest that patients such as those who participated in our study require long-term secondary prophylaxis measures. Whether these should include systematic treatment with vitamin K antagonists, new anticoagulants, or aspirin, or be tailored according to patient risk factors (including elevated D-dimer levels) needs further investigation,” said Dr. Francis Couturaud of the department of internal medicine and chest diseases, University of Brest (France) Hospital, and his associates (JAMA 2015;314:31-40).

Adults with a first episode of unprovoked VT are at much greater risk of recurrence when the standard 6 months of anticoagulation runs out, compared with those whose VT is provoked by a known, transient risk factor such as lengthy surgery, trauma with immobilization of the lower limbs, or bed rest extending longer than 72 hours.

Some experts have advocated extending anticoagulation further in such patients; but whether this is actually beneficial remains uncertain, the investigators said, because most studies have not pursued follow-up beyond the end of treatment.

The researchers performed a multicenter, double-blind trial in which 371 consecutive patients with a first episode of unprovoked PE completed 6 months of anticoagulation and then were randomly assigned to a further 18 months on either warfarin or matching placebo.

During this 18-month treatment period, the primary outcome – a composite of recurrent VT (including PE) and major bleeding – occurred in 3.3% of the warfarin group and 13.5% of the placebo group. That significant difference translated to a 78% reduction in favor of warfarin (hazard ratio, 0.22), Dr. Couturaud and his associates said.

However, after the treatment period ended, the composite outcome occurred in 17.7% of the warfarin group and 10.3% of the placebo group. Thus, the risk of recurrence returned to its normal high level once warfarin was discontinued, the study authors noted.
The study was supported by the Programme Hospitalier de Recherche Clinique (the French Department of Health) and the University Hospital of Brest (France). Dr. Couturaud reported receiving research grants, honoraria, and travel pay from Actelion, AstraZeneca, Bayer, Daiichi Sankyo, Intermune, Leo Pharma, and Pfizer, and his associates reported ties to numerous industry sources.

Related Information

• Computed tomographic pulmonary angiography (CTPA) may be useful in the diagnosis of suspected PE, wrote Dr. Gregoire Le Gal and co-authors from the University of Ottawa. Alternately, a V/Q scan may be performed. The complete accompanying article on diagnostic testing methods for suspected pulmonary embolism can be found here.

Adding an extra 18 months of warfarin therapy to the standard 6 months of anticoagulation delays the recurrence of venous thrombosis in patients who have a first episode of unprovoked pulmonary embolism – but the risk of recurrence resumes as soon as the warfarin is discontinued, according to a report published online July 7 in JAMA.

“Our results suggest that patients such as those who participated in our study require long-term secondary prophylaxis measures. Whether these should include systematic treatment with vitamin K antagonists, new anticoagulants, or aspirin, or be tailored according to patient risk factors (including elevated D-dimer levels) needs further investigation,” said Dr. Francis Couturaud of the department of internal medicine and chest diseases, University of Brest (France) Hospital, and his associates (JAMA 2015;314:31-40).

Adults with a first episode of unprovoked VT are at much greater risk of recurrence when the standard 6 months of anticoagulation runs out, compared with those whose VT is provoked by a known, transient risk factor such as lengthy surgery, trauma with immobilization of the lower limbs, or bed rest extending longer than 72 hours.

Some experts have advocated extending anticoagulation further in such patients; but whether this is actually beneficial remains uncertain, the investigators said, because most studies have not pursued follow-up beyond the end of treatment.

The researchers performed a multicenter, double-blind trial in which 371 consecutive patients with a first episode of unprovoked PE completed 6 months of anticoagulation and then were randomly assigned to a further 18 months on either warfarin or matching placebo.

During this 18-month treatment period, the primary outcome – a composite of recurrent VT (including PE) and major bleeding – occurred in 3.3% of the warfarin group and 13.5% of the placebo group. That significant difference translated to a 78% reduction in favor of warfarin (hazard ratio, 0.22), Dr. Couturaud and his associates said.

However, after the treatment period ended, the composite outcome occurred in 17.7% of the warfarin group and 10.3% of the placebo group. Thus, the risk of recurrence returned to its normal high level once warfarin was discontinued, the study authors noted.
The study was supported by the Programme Hospitalier de Recherche Clinique (the French Department of Health) and the University Hospital of Brest (France). Dr. Couturaud reported receiving research grants, honoraria, and travel pay from Actelion, AstraZeneca, Bayer, Daiichi Sankyo, Intermune, Leo Pharma, and Pfizer, and his associates reported ties to numerous industry sources.

Related Information

• Computed tomographic pulmonary angiography (CTPA) may be useful in the diagnosis of suspected PE, wrote Dr. Gregoire Le Gal and co-authors from the University of Ottawa. Alternately, a V/Q scan may be performed. The complete accompanying article on diagnostic testing methods for suspected pulmonary embolism can be found here.

Adding an extra 18 months of warfarin therapy to the standard 6 months of anticoagulation delays the recurrence of venous thrombosis in patients who have a first episode of unprovoked pulmonary embolism – but the risk of recurrence resumes as soon as the warfarin is discontinued, according to a report published online July 7 in JAMA.

“Our results suggest that patients such as those who participated in our study require long-term secondary prophylaxis measures. Whether these should include systematic treatment with vitamin K antagonists, new anticoagulants, or aspirin, or be tailored according to patient risk factors (including elevated D-dimer levels) needs further investigation,” said Dr. Francis Couturaud of the department of internal medicine and chest diseases, University of Brest (France) Hospital, and his associates (JAMA 2015;314:31-40).

Adults with a first episode of unprovoked VT are at much greater risk of recurrence when the standard 6 months of anticoagulation runs out, compared with those whose VT is provoked by a known, transient risk factor such as lengthy surgery, trauma with immobilization of the lower limbs, or bed rest extending longer than 72 hours.

Some experts have advocated extending anticoagulation further in such patients; but whether this is actually beneficial remains uncertain, the investigators said, because most studies have not pursued follow-up beyond the end of treatment.

The researchers performed a multicenter, double-blind trial in which 371 consecutive patients with a first episode of unprovoked PE completed 6 months of anticoagulation and then were randomly assigned to a further 18 months on either warfarin or matching placebo.

During this 18-month treatment period, the primary outcome – a composite of recurrent VT (including PE) and major bleeding – occurred in 3.3% of the warfarin group and 13.5% of the placebo group. That significant difference translated to a 78% reduction in favor of warfarin (hazard ratio, 0.22), Dr. Couturaud and his associates said.

However, after the treatment period ended, the composite outcome occurred in 17.7% of the warfarin group and 10.3% of the placebo group. Thus, the risk of recurrence returned to its normal high level once warfarin was discontinued, the study authors noted.
The study was supported by the Programme Hospitalier de Recherche Clinique (the French Department of Health) and the University Hospital of Brest (France). Dr. Couturaud reported receiving research grants, honoraria, and travel pay from Actelion, AstraZeneca, Bayer, Daiichi Sankyo, Intermune, Leo Pharma, and Pfizer, and his associates reported ties to numerous industry sources.

Related Information

• Computed tomographic pulmonary angiography (CTPA) may be useful in the diagnosis of suspected PE, wrote Dr. Gregoire Le Gal and co-authors from the University of Ottawa. Alternately, a V/Q scan may be performed. The complete accompanying article on diagnostic testing methods for suspected pulmonary embolism can be found here.

For the first time since the middle of the 20th century, cardiovascular disease is not the main cause of death overall in the United Kingdom, according to 2012 data published in Heart.

Cancer narrowly took the lead, with 29% of mortalities in 2012 having resulted from this disease, compared to the 28% of deaths that resulted from cardiovascular disease (CVD). But CVD remains the largest killer of women in the U.K.

In 2012, 28% of all female deaths and 32% of all male deaths were caused by CVD. The highest cause of mortality for men was cancer, with 32% of male deaths having resulted from that disease. A slightly smaller percentage of female deaths – 27% – was caused by cancer than by CVD. The Office for National Statistics (ONS), the National Records of Scotland, and the Northern Ireland Statistics and Research Agency provided the data.

Of the CVD deaths, 46%, or just under 73,500, were from coronary heart disease (CHD) and 26%, or about 41,000, were from stroke.

CVD caused more than a quarter of premature deaths – defined as deaths occurring in people younger than 75 – in men and 18% of premature deaths in women. CHD was the most common cause of premature death in U.K. men.

CVD death rates also varied per region of the United Kingdom, with higher percentages of the populations of Scotland and the north of England having died of CVD than the percentage of people living in the south of England who died from the disease, according to age-standardized death rates by local authorities. Glasgow City, Scotland, had the highest CVD mortality, with 144/100,0000 people having died prematurely and 400/100,000 people having died of the disease.

“The improvements in survival [of people with CVD] mean that there is now a high prevalence of people living with CVD,” according to Prachi Bhatnagar, Ph.D., and her colleagues.

The numbers of people suffering from CHD, stroke, atrial fibrillation and heart failure in the U.K. in 2012 and 2013 were approximately 2.3 million, 1.2 million, 1 million and 480,000, respectively, Quality of Outcomes Framework data suggest. The number of operations carried out to treat CHD is increasing in the United Kingdom, with greater than 90,000 percutaneous coronary interventions (PCIs) having been carried out in 2012 – more than twice as many as had been performed a decade earlier.

“CVD remains a substantial burden to the U.K., both in terms of health and economic costs,” according to the researchers.

Read the full study in Heart (doi:10.1136/heartjnl-2015-307516).

klennon@frontlinemedcom.com

For the first time since the middle of the 20th century, cardiovascular disease is not the main cause of death overall in the United Kingdom, according to 2012 data published in Heart.

Cancer narrowly took the lead, with 29% of mortalities in 2012 having resulted from this disease, compared to the 28% of deaths that resulted from cardiovascular disease (CVD). But CVD remains the largest killer of women in the U.K.

In 2012, 28% of all female deaths and 32% of all male deaths were caused by CVD. The highest cause of mortality for men was cancer, with 32% of male deaths having resulted from that disease. A slightly smaller percentage of female deaths – 27% – was caused by cancer than by CVD. The Office for National Statistics (ONS), the National Records of Scotland, and the Northern Ireland Statistics and Research Agency provided the data.

Of the CVD deaths, 46%, or just under 73,500, were from coronary heart disease (CHD) and 26%, or about 41,000, were from stroke.

CVD caused more than a quarter of premature deaths – defined as deaths occurring in people younger than 75 – in men and 18% of premature deaths in women. CHD was the most common cause of premature death in U.K. men.

CVD death rates also varied per region of the United Kingdom, with higher percentages of the populations of Scotland and the north of England having died of CVD than the percentage of people living in the south of England who died from the disease, according to age-standardized death rates by local authorities. Glasgow City, Scotland, had the highest CVD mortality, with 144/100,0000 people having died prematurely and 400/100,000 people having died of the disease.

“The improvements in survival [of people with CVD] mean that there is now a high prevalence of people living with CVD,” according to Prachi Bhatnagar, Ph.D., and her colleagues.

The numbers of people suffering from CHD, stroke, atrial fibrillation and heart failure in the U.K. in 2012 and 2013 were approximately 2.3 million, 1.2 million, 1 million and 480,000, respectively, Quality of Outcomes Framework data suggest. The number of operations carried out to treat CHD is increasing in the United Kingdom, with greater than 90,000 percutaneous coronary interventions (PCIs) having been carried out in 2012 – more than twice as many as had been performed a decade earlier.

“CVD remains a substantial burden to the U.K., both in terms of health and economic costs,” according to the researchers.

Read the full study in Heart (doi:10.1136/heartjnl-2015-307516).

klennon@frontlinemedcom.com

For the first time since the middle of the 20th century, cardiovascular disease is not the main cause of death overall in the United Kingdom, according to 2012 data published in Heart.

Cancer narrowly took the lead, with 29% of mortalities in 2012 having resulted from this disease, compared to the 28% of deaths that resulted from cardiovascular disease (CVD). But CVD remains the largest killer of women in the U.K.

In 2012, 28% of all female deaths and 32% of all male deaths were caused by CVD. The highest cause of mortality for men was cancer, with 32% of male deaths having resulted from that disease. A slightly smaller percentage of female deaths – 27% – was caused by cancer than by CVD. The Office for National Statistics (ONS), the National Records of Scotland, and the Northern Ireland Statistics and Research Agency provided the data.

Of the CVD deaths, 46%, or just under 73,500, were from coronary heart disease (CHD) and 26%, or about 41,000, were from stroke.

CVD caused more than a quarter of premature deaths – defined as deaths occurring in people younger than 75 – in men and 18% of premature deaths in women. CHD was the most common cause of premature death in U.K. men.

CVD death rates also varied per region of the United Kingdom, with higher percentages of the populations of Scotland and the north of England having died of CVD than the percentage of people living in the south of England who died from the disease, according to age-standardized death rates by local authorities. Glasgow City, Scotland, had the highest CVD mortality, with 144/100,0000 people having died prematurely and 400/100,000 people having died of the disease.

“The improvements in survival [of people with CVD] mean that there is now a high prevalence of people living with CVD,” according to Prachi Bhatnagar, Ph.D., and her colleagues.

The numbers of people suffering from CHD, stroke, atrial fibrillation and heart failure in the U.K. in 2012 and 2013 were approximately 2.3 million, 1.2 million, 1 million and 480,000, respectively, Quality of Outcomes Framework data suggest. The number of operations carried out to treat CHD is increasing in the United Kingdom, with greater than 90,000 percutaneous coronary interventions (PCIs) having been carried out in 2012 – more than twice as many as had been performed a decade earlier.

“CVD remains a substantial burden to the U.K., both in terms of health and economic costs,” according to the researchers.

Read the full study in Heart (doi:10.1136/heartjnl-2015-307516).

klennon@frontlinemedcom.com

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.

While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.

“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).

Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.

The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.

The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.

The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.

This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.

But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).

“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.

Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.

From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.

“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.

While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.

“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).

Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.

The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.

The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.

The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.

This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.

But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).

“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.

Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.

From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.

“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.

While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.

“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).

Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.

The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.

The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.

The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.

This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.

But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).

“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.

Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.

From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.

“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

PARIS – A novel method of quantifying the risks of major bleeding and stent thrombosis may guide decisions about the duration of dual-antiplatelet therapy in stent recipients, according to Dr. Francesco Costa.

It’s a two-pronged approach that relies upon a CRUSADE bleeding risk score greater than 40 as a red flag cautioning against 24 months of dual-antiplatelet therapy (DAPT) in favor of 6 months, while also taking into consideration the anatomic location of an individual’s coronary artery disease as a guide to ischemic risk, such as stent thrombosis, Dr. Costa said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

A patient with at least 30% luminal narrowing of the left main coronary artery and/or the proximal LAD (left anterior descending) artery is at markedly reduced risk of stent thrombosis with a DAPT regimen of 24 months rather than 6 months, according to Dr. Costa of Erasmus University in Rotterdam, the Netherlands. These findings were borne out in a retrospective analysis of data from the previously published PRODIGY trial, in which 2,013 patients undergoing percutaneous coronary intervention were randomized to receive a first- or second-generation drug-eluting stent or a bare metal stent, and then further randomized to 6 or 24 months of DAPT (Circulation 2012;125:2015-26).

As these findings about how to guide DAPT duration come from an exploratory retrospective analysis, Dr. Costa stressed, they must be considered hypothesis generating. A definitive prospective randomized trial is warranted to confirm the hypothesis. Such a trial is sorely needed, the cardiologist added.

“International guidelines suggest tailoring DAPT duration according to a patient’s ischemic and bleeding risks. However, currently a reproducible method of weighing these risks has not yet been proposed,” he said. “I think if we put 10 different [physicians] in front of a patient and asked them to define that patient’s bleeding risk, almost everyone would have a different idea.”

The PRODIGY-tested approach, while not ideal, is a definite step forward, according to Dr. Costa.

He and his coworkers evaluated three different bleeding risk scoring systems – HAS-BLED, ACUITY, and CRUSADE – before concluding that a CRUSADE score greater than 40 was superior as a predictor of major bleeding in the PRODIGY population.

Roughly 16% of participants in this all-comers study had a CRUSADE score above 40. A 24-month course of DAPT in this group was associated with a 2.7-fold increased risk of major bleeding events, compared with a 6-month course. The number-needed-to-harm with a 24-month course of DAPT was 17, compared with a number-needed-to-harm of 67 in an unselected population. In contrast, there was no significant increase in major bleeding risk with 24 months of DAPT in patients with a CRUSADE score of 40 or less.

Patients with a CRUSADE score greater than 40 also had a sharply increased need for RBC transfusion if they were on 24 months of DAPT.

The investigators chose 30% luminal narrowing of the left main or proximal LAD coronary arteries as their cutpoint for increased risk of ischemic events during follow-up because they consider it a good marker for more diffuse atherosclerotic disease.

PRODIGY participants with luminal narrowing at either location were 55% less likely to experience stent thrombosis with 24 months of DAPT than with 6.

Dr. Andreas Baumbach said the DAPT decision-making aid presented by Dr. Costa is just what interventional cardiologists have been looking for.

“We’re always talking about patients at high bleeding risk and high ischemic risk, but we haven’t really had a tool to identify those other than our clinical judgment, thinking that high bleeding risk comes with age and renal impairment. So to have a score that’s almost validated for this purpose is really important,” according to Dr. Baumbach, professor of interventional cardiology at the University of Bristol (England).

This analysis was conducted without external funding. Dr. Costa reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

PARIS – A novel method of quantifying the risks of major bleeding and stent thrombosis may guide decisions about the duration of dual-antiplatelet therapy in stent recipients, according to Dr. Francesco Costa.

It’s a two-pronged approach that relies upon a CRUSADE bleeding risk score greater than 40 as a red flag cautioning against 24 months of dual-antiplatelet therapy (DAPT) in favor of 6 months, while also taking into consideration the anatomic location of an individual’s coronary artery disease as a guide to ischemic risk, such as stent thrombosis, Dr. Costa said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

A patient with at least 30% luminal narrowing of the left main coronary artery and/or the proximal LAD (left anterior descending) artery is at markedly reduced risk of stent thrombosis with a DAPT regimen of 24 months rather than 6 months, according to Dr. Costa of Erasmus University in Rotterdam, the Netherlands. These findings were borne out in a retrospective analysis of data from the previously published PRODIGY trial, in which 2,013 patients undergoing percutaneous coronary intervention were randomized to receive a first- or second-generation drug-eluting stent or a bare metal stent, and then further randomized to 6 or 24 months of DAPT (Circulation 2012;125:2015-26).

As these findings about how to guide DAPT duration come from an exploratory retrospective analysis, Dr. Costa stressed, they must be considered hypothesis generating. A definitive prospective randomized trial is warranted to confirm the hypothesis. Such a trial is sorely needed, the cardiologist added.

“International guidelines suggest tailoring DAPT duration according to a patient’s ischemic and bleeding risks. However, currently a reproducible method of weighing these risks has not yet been proposed,” he said. “I think if we put 10 different [physicians] in front of a patient and asked them to define that patient’s bleeding risk, almost everyone would have a different idea.”

The PRODIGY-tested approach, while not ideal, is a definite step forward, according to Dr. Costa.

He and his coworkers evaluated three different bleeding risk scoring systems – HAS-BLED, ACUITY, and CRUSADE – before concluding that a CRUSADE score greater than 40 was superior as a predictor of major bleeding in the PRODIGY population.

Roughly 16% of participants in this all-comers study had a CRUSADE score above 40. A 24-month course of DAPT in this group was associated with a 2.7-fold increased risk of major bleeding events, compared with a 6-month course. The number-needed-to-harm with a 24-month course of DAPT was 17, compared with a number-needed-to-harm of 67 in an unselected population. In contrast, there was no significant increase in major bleeding risk with 24 months of DAPT in patients with a CRUSADE score of 40 or less.

Patients with a CRUSADE score greater than 40 also had a sharply increased need for RBC transfusion if they were on 24 months of DAPT.

The investigators chose 30% luminal narrowing of the left main or proximal LAD coronary arteries as their cutpoint for increased risk of ischemic events during follow-up because they consider it a good marker for more diffuse atherosclerotic disease.

PRODIGY participants with luminal narrowing at either location were 55% less likely to experience stent thrombosis with 24 months of DAPT than with 6.

Dr. Andreas Baumbach said the DAPT decision-making aid presented by Dr. Costa is just what interventional cardiologists have been looking for.

“We’re always talking about patients at high bleeding risk and high ischemic risk, but we haven’t really had a tool to identify those other than our clinical judgment, thinking that high bleeding risk comes with age and renal impairment. So to have a score that’s almost validated for this purpose is really important,” according to Dr. Baumbach, professor of interventional cardiology at the University of Bristol (England).

This analysis was conducted without external funding. Dr. Costa reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

PARIS – A novel method of quantifying the risks of major bleeding and stent thrombosis may guide decisions about the duration of dual-antiplatelet therapy in stent recipients, according to Dr. Francesco Costa.

It’s a two-pronged approach that relies upon a CRUSADE bleeding risk score greater than 40 as a red flag cautioning against 24 months of dual-antiplatelet therapy (DAPT) in favor of 6 months, while also taking into consideration the anatomic location of an individual’s coronary artery disease as a guide to ischemic risk, such as stent thrombosis, Dr. Costa said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

A patient with at least 30% luminal narrowing of the left main coronary artery and/or the proximal LAD (left anterior descending) artery is at markedly reduced risk of stent thrombosis with a DAPT regimen of 24 months rather than 6 months, according to Dr. Costa of Erasmus University in Rotterdam, the Netherlands. These findings were borne out in a retrospective analysis of data from the previously published PRODIGY trial, in which 2,013 patients undergoing percutaneous coronary intervention were randomized to receive a first- or second-generation drug-eluting stent or a bare metal stent, and then further randomized to 6 or 24 months of DAPT (Circulation 2012;125:2015-26).

As these findings about how to guide DAPT duration come from an exploratory retrospective analysis, Dr. Costa stressed, they must be considered hypothesis generating. A definitive prospective randomized trial is warranted to confirm the hypothesis. Such a trial is sorely needed, the cardiologist added.

“International guidelines suggest tailoring DAPT duration according to a patient’s ischemic and bleeding risks. However, currently a reproducible method of weighing these risks has not yet been proposed,” he said. “I think if we put 10 different [physicians] in front of a patient and asked them to define that patient’s bleeding risk, almost everyone would have a different idea.”

The PRODIGY-tested approach, while not ideal, is a definite step forward, according to Dr. Costa.

He and his coworkers evaluated three different bleeding risk scoring systems – HAS-BLED, ACUITY, and CRUSADE – before concluding that a CRUSADE score greater than 40 was superior as a predictor of major bleeding in the PRODIGY population.

Roughly 16% of participants in this all-comers study had a CRUSADE score above 40. A 24-month course of DAPT in this group was associated with a 2.7-fold increased risk of major bleeding events, compared with a 6-month course. The number-needed-to-harm with a 24-month course of DAPT was 17, compared with a number-needed-to-harm of 67 in an unselected population. In contrast, there was no significant increase in major bleeding risk with 24 months of DAPT in patients with a CRUSADE score of 40 or less.

Patients with a CRUSADE score greater than 40 also had a sharply increased need for RBC transfusion if they were on 24 months of DAPT.

The investigators chose 30% luminal narrowing of the left main or proximal LAD coronary arteries as their cutpoint for increased risk of ischemic events during follow-up because they consider it a good marker for more diffuse atherosclerotic disease.

PRODIGY participants with luminal narrowing at either location were 55% less likely to experience stent thrombosis with 24 months of DAPT than with 6.

Dr. Andreas Baumbach said the DAPT decision-making aid presented by Dr. Costa is just what interventional cardiologists have been looking for.

“We’re always talking about patients at high bleeding risk and high ischemic risk, but we haven’t really had a tool to identify those other than our clinical judgment, thinking that high bleeding risk comes with age and renal impairment. So to have a score that’s almost validated for this purpose is really important,” according to Dr. Baumbach, professor of interventional cardiology at the University of Bristol (England).

This analysis was conducted without external funding. Dr. Costa reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

bjancin@frontlinemedcom.com

PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

bjancin@frontlinemedcom.com

PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

bjancin@frontlinemedcom.com