Endogenous tissue plasminogen activator and risk of recurrent cardiac events after an acute coronary syndrome in the MIRACL study

ObjectiveTo examine the relationship of baseline tissue plasminogen activator (t-PA) to early cardiovascular risk after an acute coronary syndrome, and the effect of intensive statin therapy.MethodsWe measured plasma t-PA in 2860 of the 3086 (93%) subjects in the MIRACL study, an international randomized trial of atorvastatin 80 mg daily versus placebo in patients with acute coronary syndromes. The relationship of t-PA to death, non-fatal acute myocardial infarction, cardiac arrest, or worsening angina over 16 weeks was assessed by Cox Proportional Hazards. D-dimer was measured in a random sample of 395 subjects.ResultsHigher baseline t-PA was significantly related to the risk of recurrent events (HR = 1.25, p = 0.0014). This relationship was unaffected by adjustment for age, sex, troponin, hsCRP, and lipids (HR = 1.17, p = 0.029), but was attenuated by adjustment including body mass index and smoking (HR = 1.14, p=0.08). D-dimer and t-PA concentrations were not related. Atorvastatin reduced the risk of recurrent events, but did not affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes.ConclusionIn patients with acute coronary syndromes, increasing t-PA concentration was related to a higher early risk of recurrent events, paradoxically reflecting impaired endogenous fibrinolysis. This relationship is due in part to the association of t-PA with age, body mass index and smoking. Although statins lower the risk of recurrent events after acute coronary syndromes, it is unlikely that this benefit is achieved through thrombolytic and fibrinolytic pathways.