prasugrel-hydrochloride and Death--Sudden--Cardiac

The availability of more sensitive biomarkers of myonecrosis and a new classification system from the universal definition of myocardial infarction (MI) have led to evolution of the classification of MI. The prognostic implications of MI defined in the current era have not been well described.. We investigated the association between new or recurrent MI by subtype according to the European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation Task Force for the Redefinition of MI Classification System and the risk of cardiovascular death among 13 608 patients with acute coronary syndrome in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). The adjusted risk of cardiovascular death was evaluated by landmark analysis starting at the time of the MI through 180 days after the event. Patients who experienced an MI during follow-up had a higher risk of cardiovascular death at 6 months than patients without an MI (6.5% versus 1.3%, P<0.001). This higher risk was present across all subtypes of MI, including type 4a (peri-percutaneous coronary intervention, 3.2%; P<0.001) and type 4b (stent thrombosis, 15.4%; P<0.001). After adjustment for important clinical covariates, the occurrence of any MI was associated with a 5-fold higher risk of death at 6 months (95% confidence interval 3.8-7.1), with similarly increased risk across subtypes.. MI is associated with a significantly increased risk of cardiovascular death, with a consistent relationship across all types as defined by the universal classification system. These findings underscore the clinical relevance of these events and the importance of therapies aimed at preventing MI.

Topics: Aged; American Heart Association; Blood Platelets; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Incidence; International Cooperation; Male; Middle Aged; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Severity of Illness Index; Thiophenes; Thrombolytic Therapy; United States

Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI.. We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P<0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P=0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P=0.0013) and consistently across MI size, including MIs with a biomarker peak > or =5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P=0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P=0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P=0.0069).. Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy.

Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Biomarkers; Clopidogrel; Combined Modality Therapy; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Double-Blind Method; Humans; Incidence; Kaplan-Meier Estimate; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recurrence; Thiophenes; Ticlopidine; Time Factors; Troponin T