TRITON-TIMI 38 stent analysis demonstrates that prasugrel is better than clopidogrel in reducing the incidence of early and late stent thrombosis

March 29, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

SCAI-ACCi2 08-Chicago, IL: The TRITON-TIMI 38 stent study demonstrates that prasugrel is better than clopidogrel in reducing the incidence of early and late stent thrombosis in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI).

Dr Stephen Wiviott from the TIMI Study Group Boston, MA presented the results of the TRITON-TIMI 38 (the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel) stent study at the SCAI-i2 summit Annual Scientific Sessions in Chicago today and simultaneously the results are published in the Lancet.

The results of the TRITON TIMI-38 study was presented last year at the American Heart Association Scientific sessions in Orlando by Dr. Elliot Antman from the TIMI study group and subsequently the results were published in the New England Journal of Medicine. Patients were randomized to receive either clopidogrel (300 mg loading dose before the procedure followed by 75 mg maintenance dose for one year) or prasugrel (60 mg loading dose followed by 10 mg daily for one year). This study demonstrated that the use of prasugrel among patients undergoing PCI following an acute coronary syndrome was associated with a reduced incidence of ischemic events (reduced rates of myocardial infarction and urgent target vessel revascularization and stent thrombosis) and an increase in major bleed including fatal bleed with no difference in mortality between the two groups. Concerns are being raised on the safety and efficacy of prasugrel given the increased incidence of major fatal bleed (reference 3).

The investigators from the TIMI study group Boston performed further analysis on patients who underwent stenting to determine the efficacy of prasugrel in reducing stent thrombosis following PCI.

The stent analysis consisted of 12,844 patients (of 13,608 patients of the original cohort) who received a stent. In total 6461 patients (47%) received bare metal stent (BMS), 5743 patients (42%) received drug eluting stents (DES) and the remaining 640 patients (5%) received both. In the drug eluting stent cohort, paclitaxel eluting stents (PES) were used in 20%, cypher stent (SES) in 18% and other/mixed stents were used in 4% of cases.

Prasugrel was associated with significant reduction in the key efficacy and safety endpoints (cardiovascular death, myocardial infarction and cerebrovascular events) compared with clopidogrel both in the BMS group [10% vs. 12.2% HR 0.8 (0.69-0.93), p=0.003] and DES group [9% vs. 11.1%, HR 0.82 (0.69-0.97, p=0.02)]. There was no difference in the non-CABG TIMI major bleed in the BMS group and DES group between prasugrel and clopidogrel [2.3% vs. 1.6%, HR 13.7 (0.95-1.99), p=0.09] and [2.5% vs. 2.1%, HR 1.19 (0.83-1.72), p=0.34]. Stent thrombosis in this trial was associated with increased mortality compared to those who did not have stent thrombosis [25.9% vs. 2.6%, HR 13.1 (9.8-17.5), P<0.0001]. There was a significant reduction in the incidence of definite/probable ST with prasugrel [1.13% vs. 2.35%, HR 0.48 (0.36-0.64), p<0.0001] including the incidence of early [0.64% vs. 1.56%, HR 0.41 (0.29-0.59), p<0.0001] and late ST [0.49% vs. 0.82%, HR 0.60 (0.37-0.97), p=0.03].

Among patients who received drug eluting stents only, again prasugrel was associated with reduced ST compared with clopidogrel [0.84% vs. 2.31%, HR 0.36 (0.22-0.58), p<0.0001]. Among patients who received sirolimus eluting stent and those who received paclitaxel eluting stents, prasugrel was associated with 67% reduction in the incidence of ST compared with clopidogrel (p=0.004, and 0.002 respectively). On the hand, among those who received bare metal stent, use of prasugrel compared with clopidogrel was associated with 48% reduction in the incidence of ST (1.27% vs. 2.41%, p=0.0009). This was mainly attributed to reduction in the incidence of early ST (55% reduction with prasugrel, p=0.0009) rather than late ST (32% reduction with prasugrel, p=0.24). Prasugrel remained better than clopidogrel in a sub-analysis consisting of different patient and procedural characteristics.

Therefore the sub-analysis of the TRITON-TIMI 38 trial demonstrated that prasugrel is better in terms of reduction in the incidence of stent thrombosis (both early and late stent thrombosis) compared to clopidogrel regardless of the type of stent (bare metal or drug eluting stent), time duration following the PCI procedure or regardless of the definition used for stent thrombosis.

Source

 * 1) Late Breaking Clinical Trials Session: SCAI Annual Scientific Sessions in partnership with ACC i2 summit, March 29-April 1, 2008 Chicago
 * 2) SCAI-ACC i2 press release
 * 3) Serebruany VL. Prasugrel versus clopidogrel [letter]. New Engl J Med 2008; 358:1298.