A new post-hoc sub-analysis of an important set of patients from the TRITON-TIMI 38 study, those identified as the core clinical cohort population, showed that treatment with Prasugrel ( Effient, Efient ) ( in combination with Aspirin ) was associated with a 26% relative risk reduction in the combined primary endpoint of cardiovascular death, myocardial infarction or stroke, compared to treatment with Clopidogrel ( Plavix ) ( 8.3% vs 11.0%, respectively, p less than 0.0001 ).
This corresponds to a 2.7% absolute risk reduction for patients treated with Prasugrel.
These data were recently published in the American Journal of Cardiology.
For this analysis, investigators analyzed three patient clinical cohorts:
• The core clinical cohort: patients who were under 75 years of age, weighed 60 kg or more and who had no prior history of stroke or transient ischemic attack ( TIA ). This group ( n=10,804, 79% of all study subjects ) excluded those patients considered to be at a higher risk for bleeding by the FDA ( Food and Drug Administration ) and the EMA ( European Medicines Agency ) in their regulatory approval of Prasugrel;
• The non-core cohort: patients 75 years of age or older or patients who weighed less than 60 kg, but without known prior stroke or TIA ( n=2,149; 16% of study participants ). The use of Prasugrel in patients greater than or equal to 75 years is generally not recommended. If, after a careful individual benefit/risk evaluation by the prescribing physician, treatment is deemed necessary in the patient age group greater than or equal to 75 years, then following a 60 mg loading dose, a reduced maintenance dose of 5 mg should be prescribed;
• The third group were patients with a self-reported or known history of stroke or TIA prior to enrollment ( n=518; 4% of study participants ). Prasugrel is contraindicated in such patients;
• Patients without known prior stroke but with missing baseline weight data were excluded from the analysis as it could not be determined to which final cohort they should be assigned to ( n=137; 1% of study participants ).
In the core clinical cohort, there were higher bleeding rates in Prasugrel patients compared to Clopidogrel patients. Appropriate prescribing may help minimize a bleeding risk. Based on the post hoc analysis reported in this paper, in patients in the TRITON-TIMI 38 study who were younger than 75, heavier than 60 kg and with no prior stroke, the difference in the rates of certain types of bleeding ( known as non-CABG TIMI major bleeding ) was reduced, without adversely impacting the efficacy of Prasugrel versus Clopidogrel.
Relative bleeding rates were similar across the core and non-core groups. In the core group, the rate of TIMI major bleeding was 1.9% in Prasugrel patients compared to 1.5% in Clopidogrel patients, corresponding to a 0.4% absolute increase and a 24% relative increase in Prasugrel patients ( p=0.17 ). In the non-core group, the rate of TIMI major bleeding was 4.1% in Prasugrel patients compared to 3.4% in Clopidogrel patients, corresponding to a 0.7% absolute increase and a 23% relative increase in Prasugrel patients ( p=0.40 ).
In both cases findings were not statistically significant.
The rate of TIMI major or minor bleeding was statistically significantly greater with Prasugrel than Clopidogrel in the core group ( 3.9% vs. 3.0% respectively, p=0.033 ), but not in the non-core group ( 9.8% Prasugrel vs 7.5% Clopidogrel, p=0.08 ), although the relative increase in bleeding within these groups were similar.
The analysis found that in greater than or equal to 75 year old and low body weight ( less than 60 kg ) patients ( the non-core cohort ), event rates were high in both treatment arms ( 15.3 vs 16.3%, p=0.61, HR=0.94 ) compared to the core cohort group. Patients taking Prasugrel in the third group had non-favorable results with regard to both efficacy and safety compared to Clopidogrel, with a higher rate of primary efficacy events ( 19.1% vs 14.4%, p=0.15 ) driven by an increase in stroke and a higher rate of bleeding, including more intracranial hemorrhage ( 2.3% vs 0%, p=0.02 ). Prasugrel is contraindicated in patients who have had a prior transient ischemic attack ( TIA ) or stroke.
Source: Eli Lilly, 2011