Anticoagulation Hub

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Deficiency of the endogenous anticoagulant proteins antithrombin, protein C, and protein S are significantly associated with an increased risk of a first episode of venous thromboembolism, according to a study published in Thrombosis Research.

To determine the impact of inherited deficiency of natural anticoagulants on VTE risk, the authors performed a systematic review and meta-analysis of 21 studies comprising a total of 3,452 cases and 11,562 controls. The investigation showed a significantly increased risk of first VTE in antithrombin deficient subjects compared to controls (OR 16.26), as well as an in protein C (OR 7.51) and protein S deficient patients (OR 5.37). For VTE recurrence, they found a significant association with antithrombin (OR 3.61) and protein C deficiencies (OR 2.94), but not with protein S deficiency.

“The strength of association between the deficiency of these natural anticoagulants and the risk of a first episode of VTE . . . may justify the research of these uncommon anticoagulant deficiencies, in particular in patients with unprovoked events,” wrote Dr. Matteo Nicola Dario Di Minno of Federico II University in Naples, Italy and his associates.

Read the full article in Thrombosis Research here: (DOI: http://dx.doi.org/10.1016/j.thromres.2015.03.010)

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.

Fondaparinux was just as safe as unfractionated heparin for venous thromboembolism prophylaxis in ischemic stroke, report Dr. C.T. Hackett and co-authors of the department of neurology and Allegheny General Hospital Comprehensive Stroke Center at the University of South Carolina.

In an analysis of 644 acute ischemic stroke patients receiving either fondaparinux or unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis, major hemorrhages occurred in just 1.2% of patients in the fondaparinux group, compared with 3.7% in the UFH group. This difference was not statistically significant (P = .08). Additionally, there was no significant difference in total hemorrhage (P = .15), intracranial hemorrhage (P = .48), major extracranial hemorrhage, (P = .18) or symptomatic VTE (P = 1.00) between the two groups.

The findings “provide supportive safety data for a prospective trial of extended VTE prophylaxis with fondaparinux in acute ischemic stroke,” the authors wrote.

Read the full article in Thrombosis Research: http://dx.doi.org/10.1016/j.thromres.2014.11.041.

SAN DIEGO – The novel oral anticoagulants clearly outperformed warfarin for stroke prevention and safety endpoints in patients with atrial fibrillation and comorbid heart failure in a meta-analysis of four recent landmark Phase 3 clinical trials.

Collectively the four novel oral anticoagulants (NOACs) approved for stroke prophylaxis in nonvalvular atrial fibrillation (AF) reduced the risk of stroke and systemic embolism by 14%, compared with patients randomized to warfarin. Moreover, the NOACs decreased the risks of major bleeding and intracranial bleeding by 23% and 45%, respectively, Dr. Gianluigi Savarese reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“NOACs represent a valuable therapeutic option in patients with nonvalvular atrial fibrillation and heart failure,” concluded Dr. Savarese of Federico II University, Naples.

There has never been a randomized trial comparing a NOAC to warfarin specifically in patients with these dual diagnoses. In the absence of such a definitive study, the next best thing is a meta-analysis of the pivotal Phase 3 trials in which warfarin was compared to dabigatran (Pradaxa, the RE-LY study), apixaban (Eliquis, ARISTOTLE), rivaroxaban (Xarelto, ROCKET AF), and edoxaban (Savaysa, ENGAGE AF-TIMI 48).

The meta-analysis focused on a subset population of 26,384 randomized patients with AF and heart failure. It’s important to know how the NOACs stack up against warfarin in this population because symptomatic heart failure is common: indeed, it’s present in 30% of patients with AF. Patients with AF and comorbid heart failure are generally older, frailer, have more comorbidities, and are at higher risk of both stroke and bleeding, compared with AF patients without heart failure. Since heart failure is a recognized risk factor for reduced time in the therapeutic international normalized ratio (INR) range for patients on warfarin, it’s likely that warfarin-treated dual diagnosis patients would be exposed to further increased risks of stroke and bleeding, according to Dr. Savarese.

In the meta-analysis, in addition to the NOAC-treated patients’ significantly reduced risks of stroke, major bleeding, and intracranial bleeding, they showed a 12% decrease in total bleeding and an 8% reduction in cardiovascular death, compared with warfarin-treated controls, although neither of those latter two favorable trends achieved statistical significance.

The four NOACs didn’t differ significantly on any of the prespecified outcomes in the meta-analysis.

One audience member noted that while the relative risk reductions for stroke and major bleeding seen with the NOACs in the meta-analysis were large and impressive, the absolute risk reductions were actually quite small. For example, warfarin-treated controls in RE-LY, the first of the major trials, had a stroke/systemic embolism rate of 1.69%/year and a major bleeding rate of 3.4%/year (N. Engl. J. Med. 2009;361:1139-51), while controls in ENGAGE AF-TIMI 48 had annualized stroke and major bleeding rates of 1.5% and 3.4%, respectively (N. Engl. J. Med. 2013;369:2093-2104).

Dr. Savarese replied that he and his coinvestigators consider those absolute risk reductions to be clinically meaningful, especially in light of the enormous and rapidly growing number of patients with both AF and heart failure.

He reported having no financial conflicts regarding this meta-analysis, which was carried out free of commercial support.

[email protected]

SAN DIEGO – The novel oral anticoagulants clearly outperformed warfarin for stroke prevention and safety endpoints in patients with atrial fibrillation and comorbid heart failure in a meta-analysis of four recent landmark Phase 3 clinical trials.

Collectively the four novel oral anticoagulants (NOACs) approved for stroke prophylaxis in nonvalvular atrial fibrillation (AF) reduced the risk of stroke and systemic embolism by 14%, compared with patients randomized to warfarin. Moreover, the NOACs decreased the risks of major bleeding and intracranial bleeding by 23% and 45%, respectively, Dr. Gianluigi Savarese reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“NOACs represent a valuable therapeutic option in patients with nonvalvular atrial fibrillation and heart failure,” concluded Dr. Savarese of Federico II University, Naples.

There has never been a randomized trial comparing a NOAC to warfarin specifically in patients with these dual diagnoses. In the absence of such a definitive study, the next best thing is a meta-analysis of the pivotal Phase 3 trials in which warfarin was compared to dabigatran (Pradaxa, the RE-LY study), apixaban (Eliquis, ARISTOTLE), rivaroxaban (Xarelto, ROCKET AF), and edoxaban (Savaysa, ENGAGE AF-TIMI 48).

The meta-analysis focused on a subset population of 26,384 randomized patients with AF and heart failure. It’s important to know how the NOACs stack up against warfarin in this population because symptomatic heart failure is common: indeed, it’s present in 30% of patients with AF. Patients with AF and comorbid heart failure are generally older, frailer, have more comorbidities, and are at higher risk of both stroke and bleeding, compared with AF patients without heart failure. Since heart failure is a recognized risk factor for reduced time in the therapeutic international normalized ratio (INR) range for patients on warfarin, it’s likely that warfarin-treated dual diagnosis patients would be exposed to further increased risks of stroke and bleeding, according to Dr. Savarese.

In the meta-analysis, in addition to the NOAC-treated patients’ significantly reduced risks of stroke, major bleeding, and intracranial bleeding, they showed a 12% decrease in total bleeding and an 8% reduction in cardiovascular death, compared with warfarin-treated controls, although neither of those latter two favorable trends achieved statistical significance.

The four NOACs didn’t differ significantly on any of the prespecified outcomes in the meta-analysis.

One audience member noted that while the relative risk reductions for stroke and major bleeding seen with the NOACs in the meta-analysis were large and impressive, the absolute risk reductions were actually quite small. For example, warfarin-treated controls in RE-LY, the first of the major trials, had a stroke/systemic embolism rate of 1.69%/year and a major bleeding rate of 3.4%/year (N. Engl. J. Med. 2009;361:1139-51), while controls in ENGAGE AF-TIMI 48 had annualized stroke and major bleeding rates of 1.5% and 3.4%, respectively (N. Engl. J. Med. 2013;369:2093-2104).

Dr. Savarese replied that he and his coinvestigators consider those absolute risk reductions to be clinically meaningful, especially in light of the enormous and rapidly growing number of patients with both AF and heart failure.

He reported having no financial conflicts regarding this meta-analysis, which was carried out free of commercial support.

[email protected]

SAN DIEGO – The novel oral anticoagulants clearly outperformed warfarin for stroke prevention and safety endpoints in patients with atrial fibrillation and comorbid heart failure in a meta-analysis of four recent landmark Phase 3 clinical trials.

Collectively the four novel oral anticoagulants (NOACs) approved for stroke prophylaxis in nonvalvular atrial fibrillation (AF) reduced the risk of stroke and systemic embolism by 14%, compared with patients randomized to warfarin. Moreover, the NOACs decreased the risks of major bleeding and intracranial bleeding by 23% and 45%, respectively, Dr. Gianluigi Savarese reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

“NOACs represent a valuable therapeutic option in patients with nonvalvular atrial fibrillation and heart failure,” concluded Dr. Savarese of Federico II University, Naples.

There has never been a randomized trial comparing a NOAC to warfarin specifically in patients with these dual diagnoses. In the absence of such a definitive study, the next best thing is a meta-analysis of the pivotal Phase 3 trials in which warfarin was compared to dabigatran (Pradaxa, the RE-LY study), apixaban (Eliquis, ARISTOTLE), rivaroxaban (Xarelto, ROCKET AF), and edoxaban (Savaysa, ENGAGE AF-TIMI 48).

The meta-analysis focused on a subset population of 26,384 randomized patients with AF and heart failure. It’s important to know how the NOACs stack up against warfarin in this population because symptomatic heart failure is common: indeed, it’s present in 30% of patients with AF. Patients with AF and comorbid heart failure are generally older, frailer, have more comorbidities, and are at higher risk of both stroke and bleeding, compared with AF patients without heart failure. Since heart failure is a recognized risk factor for reduced time in the therapeutic international normalized ratio (INR) range for patients on warfarin, it’s likely that warfarin-treated dual diagnosis patients would be exposed to further increased risks of stroke and bleeding, according to Dr. Savarese.

In the meta-analysis, in addition to the NOAC-treated patients’ significantly reduced risks of stroke, major bleeding, and intracranial bleeding, they showed a 12% decrease in total bleeding and an 8% reduction in cardiovascular death, compared with warfarin-treated controls, although neither of those latter two favorable trends achieved statistical significance.

The four NOACs didn’t differ significantly on any of the prespecified outcomes in the meta-analysis.

One audience member noted that while the relative risk reductions for stroke and major bleeding seen with the NOACs in the meta-analysis were large and impressive, the absolute risk reductions were actually quite small. For example, warfarin-treated controls in RE-LY, the first of the major trials, had a stroke/systemic embolism rate of 1.69%/year and a major bleeding rate of 3.4%/year (N. Engl. J. Med. 2009;361:1139-51), while controls in ENGAGE AF-TIMI 48 had annualized stroke and major bleeding rates of 1.5% and 3.4%, respectively (N. Engl. J. Med. 2013;369:2093-2104).

Dr. Savarese replied that he and his coinvestigators consider those absolute risk reductions to be clinically meaningful, especially in light of the enormous and rapidly growing number of patients with both AF and heart failure.

He reported having no financial conflicts regarding this meta-analysis, which was carried out free of commercial support.

[email protected]

Levels of platelet distribution width (PDW) and mean platelet volume (MPV) were significantly higher in patients with pulmonary embolism, Dr. Jianqiang Huang and co-authors at the Department of Cardiovascular Medicine, Shantou Central Hospital in Guangdong Province, China, have reported.

A study of platelet indexes in 70 PE patients and 75 controls showed that PDW (16.40% vs. 16.00%) and MPV (9.91±1.40 fL vs. 8.84±1.68) values were significantly higher in those with PE, compared with controls. There were no significant differences in platelet count, the investigators reported.

The results indicate that measuring “MPV can increase the specificity and [positive predictive value] to improve the diagnostic value of D-dimer for PE,” the authors wrote. “Because platelet indexes are convenient to detect, clinical physicians may increase their vigilance to identify suspected PE,” they added.

Read the full article at the American Journal of Emergency Medicine: 10.1016/j.ajem.2015.02.043.

Levels of platelet distribution width (PDW) and mean platelet volume (MPV) were significantly higher in patients with pulmonary embolism, Dr. Jianqiang Huang and co-authors at the Department of Cardiovascular Medicine, Shantou Central Hospital in Guangdong Province, China, have reported.

A study of platelet indexes in 70 PE patients and 75 controls showed that PDW (16.40% vs. 16.00%) and MPV (9.91±1.40 fL vs. 8.84±1.68) values were significantly higher in those with PE, compared with controls. There were no significant differences in platelet count, the investigators reported.

The results indicate that measuring “MPV can increase the specificity and [positive predictive value] to improve the diagnostic value of D-dimer for PE,” the authors wrote. “Because platelet indexes are convenient to detect, clinical physicians may increase their vigilance to identify suspected PE,” they added.

Read the full article at the American Journal of Emergency Medicine: 10.1016/j.ajem.2015.02.043.

Levels of platelet distribution width (PDW) and mean platelet volume (MPV) were significantly higher in patients with pulmonary embolism, Dr. Jianqiang Huang and co-authors at the Department of Cardiovascular Medicine, Shantou Central Hospital in Guangdong Province, China, have reported.

A study of platelet indexes in 70 PE patients and 75 controls showed that PDW (16.40% vs. 16.00%) and MPV (9.91±1.40 fL vs. 8.84±1.68) values were significantly higher in those with PE, compared with controls. There were no significant differences in platelet count, the investigators reported.

The results indicate that measuring “MPV can increase the specificity and [positive predictive value] to improve the diagnostic value of D-dimer for PE,” the authors wrote. “Because platelet indexes are convenient to detect, clinical physicians may increase their vigilance to identify suspected PE,” they added.

Read the full article at the American Journal of Emergency Medicine: 10.1016/j.ajem.2015.02.043.

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.

Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.

However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.

Patrice Wendling/Frontline Medical News

Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.

Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.

The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.

There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.

One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.

The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.

The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.

He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.

Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.

The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.

Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.

About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.

The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.

[email protected]

SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.

Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.

However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.

Patrice Wendling/Frontline Medical News

Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.

Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.

The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.

There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.

One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.

The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.

The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.

He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.

Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.

The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.

Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.

About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.

The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.

[email protected]

SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.

Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.

However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.

Patrice Wendling/Frontline Medical News

Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.

Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.

The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.

There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.

One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.

The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.

The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.

He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.

Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.

The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.

Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.

About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.

The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.

[email protected]

Patient adherence to dabigatran therapy varied enormously in a nationwide study of pharmacy data, and three factors were identified that markedly enhanced adherence, according to a report published online April 14 in JAMA.

After research suggested that adherence to dabigatran was suboptimal among patients taking the drug for nonvalvular atrial fibrillation, investigators explored variations in adherence across thousands of sites using a Veterans Health Administration pharmacy database. They found that among 4,863 patients filling dabigatran prescriptions at 67 pharmacies during a 2-year period, adherence ranged from a low of 42% to a high of 93%, said Dr. Supriya Shore, a cardiology fellow at Emory University, Atlanta, and her associates.

© Graça Victoria/Thinkstockphotos.com

The single most important factor that influenced dabigatran adherence was appropriate patient selection before dispensing the drug. This was defined as the pharmacist assessing the indication for treatment and ruling out contraindications after the physician ordered the prescription, as well as checking the patient’s adherence to other medications. Pharmacist monitoring of dabigatran use and adverse events, either alone or in collaboration with the treating clinician, also boosted adherence.

In addition, pharmacists working with clinicians to identify and address nonadherence also enhanced patient adherence. Prescribing physicians may not be able to routinely monitor adherence because of their large workload and limited time during clinic visits. Having a pharmacist do so mitigated patients’ tendency to stop taking the drug when minor adverse effects developed, the investigators reported (JAMA 2015 April 14 [doi:101001/jama.2015.2761]).

“These findings suggest that such site-level practices provide modifiable targets to improve patient adherence to dabigatran, as opposed to patient characteristics that frequently cannot be modified,” Dr. Shore and her associates wrote.

This study was funded in part by VA Health Services Research & Development, an American Heart Association National Scientist Development Grant, and a Gilead Sciences Cardiovascular Research Scholars Program award. Dr. Shore reported having no financial disclosures; one of her associates reported serving as a consultant to Precision Health Economics, Medtronic, and St. Jude Medical.

Patient adherence to dabigatran therapy varied enormously in a nationwide study of pharmacy data, and three factors were identified that markedly enhanced adherence, according to a report published online April 14 in JAMA.

After research suggested that adherence to dabigatran was suboptimal among patients taking the drug for nonvalvular atrial fibrillation, investigators explored variations in adherence across thousands of sites using a Veterans Health Administration pharmacy database. They found that among 4,863 patients filling dabigatran prescriptions at 67 pharmacies during a 2-year period, adherence ranged from a low of 42% to a high of 93%, said Dr. Supriya Shore, a cardiology fellow at Emory University, Atlanta, and her associates.

© Graça Victoria/Thinkstockphotos.com

The single most important factor that influenced dabigatran adherence was appropriate patient selection before dispensing the drug. This was defined as the pharmacist assessing the indication for treatment and ruling out contraindications after the physician ordered the prescription, as well as checking the patient’s adherence to other medications. Pharmacist monitoring of dabigatran use and adverse events, either alone or in collaboration with the treating clinician, also boosted adherence.

In addition, pharmacists working with clinicians to identify and address nonadherence also enhanced patient adherence. Prescribing physicians may not be able to routinely monitor adherence because of their large workload and limited time during clinic visits. Having a pharmacist do so mitigated patients’ tendency to stop taking the drug when minor adverse effects developed, the investigators reported (JAMA 2015 April 14 [doi:101001/jama.2015.2761]).

“These findings suggest that such site-level practices provide modifiable targets to improve patient adherence to dabigatran, as opposed to patient characteristics that frequently cannot be modified,” Dr. Shore and her associates wrote.

This study was funded in part by VA Health Services Research & Development, an American Heart Association National Scientist Development Grant, and a Gilead Sciences Cardiovascular Research Scholars Program award. Dr. Shore reported having no financial disclosures; one of her associates reported serving as a consultant to Precision Health Economics, Medtronic, and St. Jude Medical.

Patient adherence to dabigatran therapy varied enormously in a nationwide study of pharmacy data, and three factors were identified that markedly enhanced adherence, according to a report published online April 14 in JAMA.

After research suggested that adherence to dabigatran was suboptimal among patients taking the drug for nonvalvular atrial fibrillation, investigators explored variations in adherence across thousands of sites using a Veterans Health Administration pharmacy database. They found that among 4,863 patients filling dabigatran prescriptions at 67 pharmacies during a 2-year period, adherence ranged from a low of 42% to a high of 93%, said Dr. Supriya Shore, a cardiology fellow at Emory University, Atlanta, and her associates.

© Graça Victoria/Thinkstockphotos.com

The single most important factor that influenced dabigatran adherence was appropriate patient selection before dispensing the drug. This was defined as the pharmacist assessing the indication for treatment and ruling out contraindications after the physician ordered the prescription, as well as checking the patient’s adherence to other medications. Pharmacist monitoring of dabigatran use and adverse events, either alone or in collaboration with the treating clinician, also boosted adherence.

In addition, pharmacists working with clinicians to identify and address nonadherence also enhanced patient adherence. Prescribing physicians may not be able to routinely monitor adherence because of their large workload and limited time during clinic visits. Having a pharmacist do so mitigated patients’ tendency to stop taking the drug when minor adverse effects developed, the investigators reported (JAMA 2015 April 14 [doi:101001/jama.2015.2761]).

“These findings suggest that such site-level practices provide modifiable targets to improve patient adherence to dabigatran, as opposed to patient characteristics that frequently cannot be modified,” Dr. Shore and her associates wrote.

This study was funded in part by VA Health Services Research & Development, an American Heart Association National Scientist Development Grant, and a Gilead Sciences Cardiovascular Research Scholars Program award. Dr. Shore reported having no financial disclosures; one of her associates reported serving as a consultant to Precision Health Economics, Medtronic, and St. Jude Medical.

About a quarter of U.S. atrial fibrillation patients under 60 years old and in otherwise good health received oral anticoagulants contrary to guidelines, according to a research letter from Dr. Jonathan Hsu of the University of California, San Diego, and his associates.

In patients in the National Cardiovascular Data Registry’s PINNACLE (Practice Innovation and Clinical Excellence) registry who had a CHADS₂ and CHA2DS2-VASc score of zero, the average age of those who received oral anticoagulants was just under 51 years, compared with just over 46 years for those who did not receive oral anticoagulants. In addition to age, higher body mass index and having Medicare or no insurance vs. private insurance were associated with a higher prescription chance.

Patients treated in the South were significantly less likely to be prescribed anticoagulants than were those treated in the Northeast.

“Prescription of oral anticoagulants by cardiovascular specialists in a significant proportion of patients at the lowest thrombotic risk suggests that these health care professionals may not be fully aware of the potential risks associated with oral anticoagulation or the particularly low risk of stroke in this population,” the investigators concluded. Find the full research letter in JAMA Internal Medicine (doi:10.1001/jamainternmed.2015.0920).

About a quarter of U.S. atrial fibrillation patients under 60 years old and in otherwise good health received oral anticoagulants contrary to guidelines, according to a research letter from Dr. Jonathan Hsu of the University of California, San Diego, and his associates.

In patients in the National Cardiovascular Data Registry’s PINNACLE (Practice Innovation and Clinical Excellence) registry who had a CHADS₂ and CHA2DS2-VASc score of zero, the average age of those who received oral anticoagulants was just under 51 years, compared with just over 46 years for those who did not receive oral anticoagulants. In addition to age, higher body mass index and having Medicare or no insurance vs. private insurance were associated with a higher prescription chance.

Patients treated in the South were significantly less likely to be prescribed anticoagulants than were those treated in the Northeast.

“Prescription of oral anticoagulants by cardiovascular specialists in a significant proportion of patients at the lowest thrombotic risk suggests that these health care professionals may not be fully aware of the potential risks associated with oral anticoagulation or the particularly low risk of stroke in this population,” the investigators concluded. Find the full research letter in JAMA Internal Medicine (doi:10.1001/jamainternmed.2015.0920).

About a quarter of U.S. atrial fibrillation patients under 60 years old and in otherwise good health received oral anticoagulants contrary to guidelines, according to a research letter from Dr. Jonathan Hsu of the University of California, San Diego, and his associates.

In patients in the National Cardiovascular Data Registry’s PINNACLE (Practice Innovation and Clinical Excellence) registry who had a CHADS₂ and CHA2DS2-VASc score of zero, the average age of those who received oral anticoagulants was just under 51 years, compared with just over 46 years for those who did not receive oral anticoagulants. In addition to age, higher body mass index and having Medicare or no insurance vs. private insurance were associated with a higher prescription chance.

Patients treated in the South were significantly less likely to be prescribed anticoagulants than were those treated in the Northeast.

“Prescription of oral anticoagulants by cardiovascular specialists in a significant proportion of patients at the lowest thrombotic risk suggests that these health care professionals may not be fully aware of the potential risks associated with oral anticoagulation or the particularly low risk of stroke in this population,” the investigators concluded. Find the full research letter in JAMA Internal Medicine (doi:10.1001/jamainternmed.2015.0920).

SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.

Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.

However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).

The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).

“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.

Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.

The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.

TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.

The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).

“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.

Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.

“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”

Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).

When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.

The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.

Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.

As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.

Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.

“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”

Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.

On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.

TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.

[email protected]

SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.

Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.

However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).

The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).

“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.

Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.

The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.

TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.

The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).

“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.

Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.

“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”

Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).

When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.

The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.

Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.

As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.

Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.

“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”

Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.

On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.

TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.

[email protected]

SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.

Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.

However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).

The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).

“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.

Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.

The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.

TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.

The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).

“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.

Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.

“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”

Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).

When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.

The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.

Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.

As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.

Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.

“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”

Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.

On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.

TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.

[email protected]