In the Journals

Low-dose prasugrel not superior to clopidogrel in elderly patients with ACS

Clinical outcomes did not differ significantly between elderly patients with ACS undergoing PCI who received low-dose prasugrel and those who received standard-dose clopidogrel, data from the Elderly ACS-2 study suggest.

Based on pharmacokinetic data, the lower, 5-mg dose of prasugrel (Effient, Daiichi Sankyo/Eli Lilly) has been recommended for treatment of elderly patients to address the bleeding risks associated with dual antiplatelet therapy in this patient population. However, little data exist on the reduced dose in elderly patients with ACS undergoing PCI, the researchers wrote.

In the multicenter, open-label, blinded-endpoint Elderly ACS-2 trial, the researchers sought to determine whether reduced-dose prasugrel offered more clinical benefit when compared with standard-dose clopidogrel, plus aspirin, in elderly patients (aged 75 years or older; mean age, 81 years; 40% women) with ACS after early PCI.

In addition to aspirin, patients were randomly assigned to a daily maintenance dose of prasugrel 5 mg (n = 713) or clopidogrel 75 mg (n = 730) from 2012 to 2017. The primary endpoint was a composite of mortality, MI, disabling stroke and rehospitalization for CV causes or bleeding at 1 year. Median follow-up was 12.1 months.

The primary endpoint occurred in 17% of the prasugrel group and 16.6% of the clopidogrel group (HR = 1.007; 95% CI, 0.78-1.3), with no difference in occurrence of the primary endpoint among clinically relevant subgroups.

Fewer cases of definite or probable stent thrombosis occurred in the prasugrel group compared with the clopidogrel group (0.7% vs. 1.9%; OR = 0.36; 95% CI, 0.13-1), according to the data. Additionally, stent thrombosis was numerically more frequent with clopidogrel in all clinically relevant subgroups.

Rates of Bleeding Academic Research Consortium types 2, 3 and 5 were 4.1% in the prasugrel group vs. 2.7% in the clopidogrel group (HR = 1.53; 95% CI, 0.85-3.16).

Trial enrollment was interrupted in January 2017, after enrollment of 1,443 patients, due to futility for efficacy. The final analysis is therefore underpowered due to a lower-than-expected event rate and a lower-than-planned number of patients enrolled, the researchers wrote, noting that their results should be interpreted in the context of the trial’s premature termination.

“The study adds clinical data to the existing Guideline recommendations that a reduced 5 mg prasugrel dose can be used as an alternative to clopidogrel in elderly ACS patients after PCI, though without overall clinical benefit,” they wrote. “In terms of actual event rates and complications, the present trial provides original information on the antiplatelet therapy of elderly ACS patients treated with PCI, reducing the knowledge gaps in this growing, but still poorly represented in clinical trials, population.” – by Melissa Foster

Disclosure: The study was partially funded by Eli Lilly and Daiichi Sankyo. Please see the full study for a list of the authors’ relevant financial disclosures.

Clinical outcomes did not differ significantly between elderly patients with ACS undergoing PCI who received low-dose prasugrel and those who received standard-dose clopidogrel, data from the Elderly ACS-2 study suggest.

Based on pharmacokinetic data, the lower, 5-mg dose of prasugrel (Effient, Daiichi Sankyo/Eli Lilly) has been recommended for treatment of elderly patients to address the bleeding risks associated with dual antiplatelet therapy in this patient population. However, little data exist on the reduced dose in elderly patients with ACS undergoing PCI, the researchers wrote.

In the multicenter, open-label, blinded-endpoint Elderly ACS-2 trial, the researchers sought to determine whether reduced-dose prasugrel offered more clinical benefit when compared with standard-dose clopidogrel, plus aspirin, in elderly patients (aged 75 years or older; mean age, 81 years; 40% women) with ACS after early PCI.

In addition to aspirin, patients were randomly assigned to a daily maintenance dose of prasugrel 5 mg (n = 713) or clopidogrel 75 mg (n = 730) from 2012 to 2017. The primary endpoint was a composite of mortality, MI, disabling stroke and rehospitalization for CV causes or bleeding at 1 year. Median follow-up was 12.1 months.

The primary endpoint occurred in 17% of the prasugrel group and 16.6% of the clopidogrel group (HR = 1.007; 95% CI, 0.78-1.3), with no difference in occurrence of the primary endpoint among clinically relevant subgroups.

Fewer cases of definite or probable stent thrombosis occurred in the prasugrel group compared with the clopidogrel group (0.7% vs. 1.9%; OR = 0.36; 95% CI, 0.13-1), according to the data. Additionally, stent thrombosis was numerically more frequent with clopidogrel in all clinically relevant subgroups.

Rates of Bleeding Academic Research Consortium types 2, 3 and 5 were 4.1% in the prasugrel group vs. 2.7% in the clopidogrel group (HR = 1.53; 95% CI, 0.85-3.16).

Trial enrollment was interrupted in January 2017, after enrollment of 1,443 patients, due to futility for efficacy. The final analysis is therefore underpowered due to a lower-than-expected event rate and a lower-than-planned number of patients enrolled, the researchers wrote, noting that their results should be interpreted in the context of the trial’s premature termination.

“The study adds clinical data to the existing Guideline recommendations that a reduced 5 mg prasugrel dose can be used as an alternative to clopidogrel in elderly ACS patients after PCI, though without overall clinical benefit,” they wrote. “In terms of actual event rates and complications, the present trial provides original information on the antiplatelet therapy of elderly ACS patients treated with PCI, reducing the knowledge gaps in this growing, but still poorly represented in clinical trials, population.” – by Melissa Foster

Disclosure: The study was partially funded by Eli Lilly and Daiichi Sankyo. Please see the full study for a list of the authors’ relevant financial disclosures.