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Published on 16 August 2011

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Effient® shows significant reduction in CV events

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Prasugrel shows significant reduction in cardiovascular events compared to clopidogrel, according to a study published in the American Journal of Cardiology.

A new post-hoc sub-analysis of an important set of patients from the TRITON-TIMI 38 study showed that treatment with prasugrel (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 (8.3% vs. 11.0%, respectively, p<0.0001).

This corresponds to a 2.7% absolute risk reduction for patients treated with prasugrel. The results of this analysis, which also examined clinical outcomes in two other cohorts of patients who were treated for acute coronary syndromes (ACS) and underwent angioplasty with stenting, will help inform appropriate physician prescribing of prasugrel.

For this analysis, investigators analysed three patient clinical cohorts:
·  The core clinical cohort: Patients who were under 75-years-old, 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 U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in their regulatory approval of prasugrel and as outlined in prescribing labels for prasugrel tablets in these regions.

·  The non-core cohort: Patients 75-years-old 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 ≥ 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 ≥ 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 enrolment (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 (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 minimise 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 versus the overall population, 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.

“This analysis showed that the use of prasugrel in a clinically identifiable population of ACS patients undergoing PCI in the TRITON-TIMI 38 trial significantly improved cardiovascular outcomes,” said Stephen Wiviott, lead author of the paper.

The analysis found that in ≥75 year old and low body weight (<60kg) patients (the non-core cohort), event rates (cardiovascular death, myocardial infarction, or stroke) 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-favourable 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 haemorrhage (2.3% vs. 0%, p=0.02).

Prasugrel is contraindicated in patients who have had a prior transient ischemic attack (TIA) or stroke.

American Journal of Cardiology



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