Selecting antiplatelet therapy at the time of percutaneous intervention for an
acute coronary syndrome: weighing the benefits and risks of prasugrel versus
clopidogrel.
Author(s): Salisbury AC(1), Wang K, Cohen DJ, Li Y, Jones PG, Spertus JA.
Affiliation(s): Author information:
(1)Saint Luke's Mid America Heart and Vascular Institute, and University of
Missouri-Kansas City, Kansas City, MO 64111, USA. salisburya@umkc.edu
Publication date & source: 2013, Circ Cardiovasc Qual Outcomes. , 6(1):27-34
BACKGROUND: On average, acute coronary syndrome patients treated with prasugrel
experience fewer ischemic complications, but more bleeding, than those receiving
clopidogrel. However, heterogeneity in treatment effects can alter the likelihood
of benefits and risks of an individual patient. We developed predictive models of
the benefits (reduced ischemic events) and risks (increased bleeding) to support
targeting prasugrel to those who benefit most from treatment.
METHODS AND RESULTS: Using 12 579 patients from Trial to Assess Improvement in
Therapeutic Outcomes by Optimizing Platelet Inhibition With
Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38), we fit risk
models for ischemic events (cardiovascular death, spontaneous myocardial
infarction, stroke) and bleeding (TIMI major/minor) over a 14.8-month follow-up
and then calculated each patient's predicted risk for major ischemia and bleeding
with both prasugrel and clopidogrel. We found substantial heterogeneity of the
treatment effect of prasugrel (mean absolute reduction in the ischemia risk with
prasugrel=1.5±3.0%, ranging from an 8.4% increased risk to a 31.2% reduction in
risk for ischemia compared with clopidogrel). The mean absolute increase in the
bleeding risk with prasugrel versus clopidogrel was 1.3±1.4% and ranged from a
7.9% lower risk to an 11.2% higher risk with prasugrel. The ratio of the
difference in predicted ischemia risk/difference in predicted bleeding risk
between prasugrel and clopidogrel was calculated for each patient to identify the
proportion likely to benefit from prasugrel. Considering both ischemia and
bleeding risk, a large proportion of TRITON participants (42%) were predicted to
experience net benefit with prasugrel, a rate that increased if patients more
strongly preferred avoiding ischemic events than bleeding.
CONCLUSIONS: The expected benefits and risks of prasugrel versus clopidogrel
depend highly on patient characteristics. The use of risk models could support
individualized thienopyridine selection to maximize the benefits and safety of
these drugs.
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