Louis Kuritzky, MD Clinical Assistant Professor, Family Medicine Residency Program, University of Florida, Gainesville, FL
José G. Díez, MD, FACC, FSCAI Clinical Associate Professor of Medicine, Cardiology/Baylor Heart Clinic, Baylor College of Medicine, Senior Research Scientist, Interventional Cardiology, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, TX
References
Findings from TRITON TIMI 38 show that, compared with clopidogrel, prasugrel was associated with significantly reduced rates of ischemic events, including nonfatal MI and stent thrombosis. The benefit with prasugrel was primarily due to a significant reduction in the rate of MI compared with clopidogrel. However, patients treated with prasugrel experienced a higher rate of major bleeding, including fatal and life-threatening bleeding. Prasugrel was found to be more effective than clopidogrel in preventing ischemic events without excess bleeding in patients with STEMI undergoing secondary PCI (treated between 12 hours and 14 days after symptom onset). In patients with ACS undergoing PCI without stent implantation, ischemic events occurred at similar rates in patients treated with prasugrel or clopidogrel; however, bleeding was more common with prasugrel.
Not all patients benefited from prasugrel therapy. Compared with clopidogrel, patients with previous stroke/transient ischemic attack (TIA) had net harm from prasugrel. In addition, no net benefit from prasugrel compared with clopidogrel was observed in patients age ≥75 years or body weight <60 kg. The results of TRITON TIMI 38 contributed to the boxed warnings regarding bleeding risk recommending that prasugrel not be used in patients age ≥75 years, in patients with active pathological bleeding or a history of TIA or stroke, or patients likely to undergo coronary artery bypass graft (CABG) surgery. In addition, patients with body weight < 60 kg are also at increased risk for bleeding.6
Primary end point (CV death, nonfatal MI, or nonfatal stroke): Cl 17.1% vs Pr 14.2% (P = .27) Urgent target-vessel revascularization: Cl 8.2% vs Pr 3.6% (P = .04)
Safety Outcomes
Non-CABG TIMI major bleeding: Cl 1.8% vs Pr 2.4% (P = .03) Fatal bleeding: Cl 0.1% vs Pr 0.4% (P = .002) Life-threatening bleeding: Cl 0.9% vs Pr 1.4% (P = .01) Non-fatal bleeding: Cl 0.9% vs Pr 1.1% (P = .23)
TIMI major bleedinga unrelated to CABG:
30 days: Cl 1.3% vs Pr 1.0% (P = .3359)
15 mos: Cl 2.1% vs. Pr 2.4% (P = .6451)
TIMI major bleedinga unrelated to CABG: Cl 0% vs Pr 2.1% (P = .03)
Key Findings
Prasugrel was associated with significantly reduced rates of ischemic events, including nonfatal MI and stent thrombosis, but with an increased risk of major bleeding, including fatal and life-threatening bleeding. Compared to clopidogrel, patients with previous stroke/TIA had net harm from prasugrel; patients with age ≥ 75 y had no net benefit from prasugrel; patients with BW < 60 kg had no net benefit from prasugrel.
Net clinical outcome All-cause death, MI, stroke, TIMI major bleeding unrelated to CABG:
30 days: Cl 10.7% vs Pr 7.4% (P = .0009)
15 mos: Cl 14.6% vs Pr 12.2% (P = .0218)
In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel in preventing ischemic events without excess bleeding.
In patients with ACS undergoing PCI without stent implantation, ischemic events occurred at similar rates in patients treated with prasugrel or clopidogrel; however, bleeding was more common with prasugrel.
ACS, acute coronary syndrome; BW, body weight; CABG, coronary artery bypass graft; Cl, clopidogrel; CV, cardiovascular; LD, loading dose; MI, myocardial infarction; PCI, percutaneous coronary intervention; Pr, prasugrel; QD, once daily; STEMI, ST-segment elevation in myocardial infarction; TIA, transient ischemic attack; TIMI, thrombolysis in myocardial infarction. aTIMI major bleed (intracranial bleed or intrapericardial bleed with cardiac tamponade or a decline of 5.0 g/dL or more in hemoglobin after adjusting for red blood cell transfusions).
