AJC: Prasugrel safe and effective, but only when indicated
Stick to the guidelines when it comes to treating patients with prasugrel, a study published Aug. 4 in the American Journal of Cardiology found. The results showed that patients with stroke and transient ischemic attack (those which are contraindicated by the FDA and European Medicines Agency) fared worse than a clinical cohort of patients with acute coronary syndromes undergoing PCI.
In July 2009, the FDA approved the antiplatelet prasugrel (Effient, Daiichi Sankyo) for the reduction of thrombotic cardiovascular events in acute coronary syndromes patients who are undergoing PCI. However, the agency included a boxed warning on the drug cautioning usage in patients with a previous stroke or transient ischemic attack (TIA), due to the potential risk of bleeding. The agencies recommended limited use or a reduced dose in patients over the age of 75 and who weighed less than 60 kg.
To assess the clinical outcomes of prasugrel in patients, Steven D. Wiviott, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues identified three groups of patients: group I (core clinical group), group II (non-core cohort) and group III (contraindicated) from the TRITON-TIMI 38 trial.
Wiviott and colleagues used a survival analysis to compare outcomes by treatment assignment (either prasugrel or clopidogrel) and by cohort (groups I and II or III). The TRITON-TIMI 38 trial included 13,608 patients. The population included 10,804 patients in group I, 2,149 patients in group II and 518 patients in group III.
Subjects in group I were younger, heavier and had no prior history of stroke or TIA. The researchers found that patients in group I who were treated with prasugrel compared to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) saw a large difference in the primary endpoint (cardiovascular death, MI or stroke). These numbers were 8.3 percent for those administered prasugrel and 11 percent for those administered clopidogrel. Group II had more neutral outcomes, 15.3 percent for those treated with prasugrel and 16.3 percent for those treated with clopidogrel.
The authors found that outcomes for patients in group III (those with a previous stroke or TIA) were worse with prasugrel, 19.1 percent versus 14.4 percent with clopidogrel, with no evidence of decreased CV death or MI. Rates of stroke were also higher in the prasugrel group, 7.2 percent versus 1.3 percent. However, group I saw a greater rate of major TIMI bleeds with prasugrel compared to clopidogrel, 1.9 percent versus 1.5 percent.
“These data suggest that prasugrel has a favorable risk-to-benefit ratio in patients without three easily identifiable clinical characteristics at baseline, i.e., in group I. In this group there appears to be an early benefit with limited bleeding liability within the first 30 days and a persistent late benefit after 30 days,” the authors wrote.
The authors said that a limitation of the study was the fact that the subgroups examined were identified in a post-hoc fashion based on regulatory action by the FDA and the EMA.
“These data indicate that use of prasugrel in a core clinical cohort that has been defined by regulatory action will maximize the benefit of prasugrel and limit the risk of adverse outcomes,” the authors summed.
In July 2009, the FDA approved the antiplatelet prasugrel (Effient, Daiichi Sankyo) for the reduction of thrombotic cardiovascular events in acute coronary syndromes patients who are undergoing PCI. However, the agency included a boxed warning on the drug cautioning usage in patients with a previous stroke or transient ischemic attack (TIA), due to the potential risk of bleeding. The agencies recommended limited use or a reduced dose in patients over the age of 75 and who weighed less than 60 kg.
To assess the clinical outcomes of prasugrel in patients, Steven D. Wiviott, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues identified three groups of patients: group I (core clinical group), group II (non-core cohort) and group III (contraindicated) from the TRITON-TIMI 38 trial.
Wiviott and colleagues used a survival analysis to compare outcomes by treatment assignment (either prasugrel or clopidogrel) and by cohort (groups I and II or III). The TRITON-TIMI 38 trial included 13,608 patients. The population included 10,804 patients in group I, 2,149 patients in group II and 518 patients in group III.
Subjects in group I were younger, heavier and had no prior history of stroke or TIA. The researchers found that patients in group I who were treated with prasugrel compared to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) saw a large difference in the primary endpoint (cardiovascular death, MI or stroke). These numbers were 8.3 percent for those administered prasugrel and 11 percent for those administered clopidogrel. Group II had more neutral outcomes, 15.3 percent for those treated with prasugrel and 16.3 percent for those treated with clopidogrel.
The authors found that outcomes for patients in group III (those with a previous stroke or TIA) were worse with prasugrel, 19.1 percent versus 14.4 percent with clopidogrel, with no evidence of decreased CV death or MI. Rates of stroke were also higher in the prasugrel group, 7.2 percent versus 1.3 percent. However, group I saw a greater rate of major TIMI bleeds with prasugrel compared to clopidogrel, 1.9 percent versus 1.5 percent.
“These data suggest that prasugrel has a favorable risk-to-benefit ratio in patients without three easily identifiable clinical characteristics at baseline, i.e., in group I. In this group there appears to be an early benefit with limited bleeding liability within the first 30 days and a persistent late benefit after 30 days,” the authors wrote.
The authors said that a limitation of the study was the fact that the subgroups examined were identified in a post-hoc fashion based on regulatory action by the FDA and the EMA.
“These data indicate that use of prasugrel in a core clinical cohort that has been defined by regulatory action will maximize the benefit of prasugrel and limit the risk of adverse outcomes,” the authors summed.