TRITON-TIMI 38: Reduction in Events, Increase in Bleeding   
      
Key Points:

Subgroup analysis found that diabetic patients assigned prasugrel had a greater relative risk reduction for MI than with clopidogrel.

By TCT Daily Staff

A recent data analysis from TRITON-TIMI 38 confirmed earlier reports of reductions in cardiac events with prasugrel vs. clopidogrel, as well as a slightly increased risk of bleeding, in patients with acute coronary syndrome undergoing PCI.

Subgroup analysis within the population of 13,600 patients enrolled in the study confirmed earlier reports (see Figures 1 and 2 for data from ESC 2008) and further defined the benefits and risks associated with prasugrel (Effient, Daiichi Sankyo and Eli Lilly) compared with clopidogrel (Plavix, Sanofi-Aventis and Bristol-Myers Squibb), according to Stephen D. Wiviott, MD, of Brigham and Women’s Hospital in Boston.

"This study largely serves as a proof of concept that more intensive, more rapid, and more consistent inhibition of platelet aggregation results in improved clinical outcomes, as well as more bleeding," he said.

Reductions in MACE

According to Wiviott, prasugrel has a more rapid onset of action than clopidogrel, and it is this property that could explain both reductions in MACE and increases in bleeding events. However, a landmark analysis, looking specifically at timing of events after PCI, showed continued reduction in ischemic events past three days – a time point at which patients could be expected to reach a "steady state," according to Wiviott.

Similar results were seen in major bleeding events. "The increase in bleeding was seen both early and late, and it seems the greater dominance of the bleeding excess was seen during the follow-up period," Wiviott said.

Subgroup analysis: Patients with diabetes

The subgroup analysis of TRITON-TIMI 38 demonstrated that patients with diabetes may derive a greater benefit with prasugrel because of higher platelet aggregation at baseline, according to Wiviott. In that population, there was a 4.8% absolute reduction in CV events or stroke and no increase in major bleeding, Wiviott said.

"It is uncertain if this finding with major bleeding was a chance finding or whether this finding with major bleeding has some biological plausibility," Wiviott said.

Further analysis of major and minor bleeding demonstrated a slightly increased risk in patients given prasugrel compared with clopidogrel. Patients with diabetes assigned to prasugrel had a greater risk reduction for MI than those assigned clopidogrel (HR=0.60, 0.48-0.76; P<.001) as did patients without diabetes (HR=0.82, 0.72-0.95; P=.006).

A 26% risk reduction was seen in the combined endpoint of MI, CVA, and major bleeding in diabetic patients assigned prasugrel compared with those assigned clopidogrel (HR=0.74, 0.62-0.89; P=.001) and an 8% reduction in risk for this endpoint in nondiabetic patients assigned prasugrel vs. clopidogrel (HR=0.92, 0.82-1.03; P=.16).

STEMI and MI

A total of 3,534 patients with STEMI were enrolled in TRITON-TIMI 38 following PCI: 2,438 (69%) after primary PCI and 1,094 after secondary PCI.

Results again favored treatment with prasugrel. TIMI major or minor bleeding was more frequent in the prasugrel group (5.1% vs. 4.7% clopidogrel; HR=1.07, 0.79-1.47) at 15 months. However, the difference was not statistically significant (P=.65).

Efficacy analysis

There has been concern that MIs prevented by prasugrel are largely periprocedural with questionable clinical relevance, Wiviott said. However, an efficacy analysis of MI events, broken down by ESC/ACC/AHA/WHF classifications, showed consistently lower incidence in patients assigned prasugrel with all types of MI except peri-CABG infarctions.

Wiviott reported a 0.1% cumulative incidence of peri-CABG infarctions in prasugrel-treated patients and none in clopidogrel-treated patients.

Patients in TRITON-TIMI 38 were representative of "patients across the spectrum of acute coronary syndrome" and were assigned either a 300-mg loading dose of clopidogrel plus 75 mg daily or a 60-mg loading dose of prasugrel plus 10 mg daily.

Patients were followed for a median 12 months and up to a maximum of 15 months.

Disclosures:

Dr. Wiviott reports receipt of research funding from Daiichi Sankyo and Eli Lilly and Company, sponsors of the TRITON-TIMI 38 trial. Dr. Wiviott has also received honoraria from Daiichi Sankyo and Eli Lilly. 
 

（source：www.tctmd.com）