Prasugrel is novel third-generation thienopyridine which is a more potent blocker of the platelet P2Y₁₂ receptor than clopidogrel.The TRITON-TIMI 38 (Trial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibition with prasugrel – Thrombolysis in Myocardial Infarction 38) study compared clopidogrel with prasugrel in the setting of ST elevation myocardial infarction (STEMI).

3534 patients with STEMI were randomly assigned to either prasugrel (60mg loading, 10mg maintenance [n=1769]) or clopidogrel (300mg loading, 75mg maintenance [n=1765]) in a double-blind fashion. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.

At 30 days, 6.5% of the patients given prasugrel had reached the primary endpoint compared with 9.5% given clopidogrel (p=0.0017) – this effect continued at 15 months (10.0% vs 12.4%, p=0.0221). The secondary endpoint of cardiovascular death, myocardial infarction, stent thrombosis, or urgent target vessel revascularisation was also significantly reduced at 30 days in patients who received prasugrel (hazard ratio 0.75, p=0.0205) – again this advantage continued up to 15 months (hazard ratio 0.79; p=0.0250). Major bleeding rates in patients who did not undergo bypass surgery did not differ between the two treatment groups at 30 days (p=0.3359) and 15 months (p=0.6451), however bleeding after surgery was greater in the prasugrel group (p=0.0033). Minor bleeding rates showed no differences between groups.

A limitation of the trial is that 600mg of clopidogrel was not used as a loading dose (as is used in many centres), and only 27% of patients were preloaded. This is important as the 30-day reduction in major cardiovascular events seen in the prasugrel arm is similar to that seen when clopidogrel was adequately preloaded in other trials (e.g. PCI-CURE). Nonetheless, for showing that more powerful platelet inhibition is capable of improving outcomes in STEMI, without necessarily increasing bleeding rates, TRITON-TIMI 38 is an important study.

• Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-segment elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomized controlled trial. Lancet 2009; 373:723-31.
• Stone GW. Ischemia versus bleeding: The art of clinical decision-making. Lancet 2009; 373:695-696.