Antiplatelet Therapies Following Placement of Drug-Eluting Stents: Which Ones and for How Long?

Luis Gruberg, MD, FACC


July 29, 2008

In This Article


The most feared complication following the advent of coronary stents has been (and continues to be) stent thrombosis. In the early days of bare metal stents (BMS), high-pressure stent deployment in combination with clopidogrel (and aspirin) lowered the risk for stent thrombosis, suggesting that platelet activity was largely related to the development of these events.[1] Despite the use of dual-antiplatelet therapy, however, 20% to 25% of patients still developed in-stent restenosis. The introduction of drug-eluting stents (DES) reduced the need for subsequent interventions but also established the important practice of administering long-term dual-antiplatelet therapy to reduce the risk for late and very late stent thrombosis.[1] The risk for bleeding associated with long-term use of dual antiplatelet therapy, lack of patient adherence to therapy, and recent findings suggesting a variability in response to clopidogrel remain ongoing concerns and active areas of study and have led to the development of novel agents and management strategies to improve patient outcomes. Some of the key studies on this important topic, presented at the American College of Cardiology (ACC) 57th Annual Scientific Session, are summarized below.


TRITON-TIMI 38 Stent Analysis: Prasugrel vs Clopidogrel in ACS Patients Undergoing PCI With Stenting

Presenter: Stephen D. Wiviott, MD (Brigham and Women's Hospital; Boston, Massachusetts)[2]


Figure 1.  (click image to zoom)

TRITON-TIMI 38: Stent Thrombosis Rates.



In addition, when stent thrombosis rates were analyzed according to the Academic Research Consortium (ARC) definitions, there was a significantly higher rate of all categories of stent thrombosis in patients treated with clopidogrel (Figure 2). A multivariate analysis showed that prasugrel was more effective in all subgroups of patients.


Figure 2.  (click image to zoom)

TRITON-TIMI 38: stent thrombosis rates according to ARC definitions.



In patients treated with DES, the use of prasugrel was associated with a 64% reduction in the rate of definite or probable stent thrombosis (Figure 3). The rate of the combined endpoint of definite/probable early and late stent thrombosis in DES patients treated with prasugrel was also significantly lower (Figure 3). This 64% reduction in the rate of stent thrombosis was seen regardless of the type of DES used (sirolimus or paclitaxel).


Figure 3.  (click image to zoom)

TRITON-TIMI 38: stent thrombosis rates in DES-treated patients.



Prasugrel was also associated with a 48% reduction in the rate of definite or probable stent thromboses in patients treated with BMS (Figure 4).


Figure 4.  (click image to zoom)

TRITON-TIMI 38: stent thrombosis rates in BMS-treated patients.



Conclusions. Intensive antiplatelet therapy with prasugrel in patients undergoing stenting showed a substantial reduction in stent thrombosis rates, regardless of the stent type, stent thrombosis definition, or early or late occurrence of stent thrombosis; the findings remained consistent across a broad range of clinical/procedural variables.



As noted by the study's discussant, George Dangas, MD, PhD (Columbia University Medical Center; New York, NY), this is the first substudy of the TRITON TIMI 38 trial to investigate the role of an alternative antiplatelet regimen for the prevention of early and late stent thrombosis. In short, the study showed that stent thrombosis can be suppressed by intensive antiplatelet therapy, but it cannot be avoided completely. This study did not assess very late stent thrombosis, however, and there was an increase in bleeding complications in patients assigned to prasugrel.


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