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Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
FROM ACC 17
Key clinical point: The risk of major bleeding was similar between acute coronary syndrome patients treated with a combination of low-dose rivaroxaban and P2Y12 inhibitor and those treated with aspirin and P2Y12 inhibitor.
Major finding: Clinically significant bleeding occurred in 5% of patients in each treatment group (HR, 1.09).
Data source: A double-blind, multicenter, randomized trial (GEMINI ACS 1) including 3,037 adults.
Disclosures: The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.