Document Detail

Endogenous tissue plasminogen activator and risk of recurrent cardiac events after an acute coronary syndrome in the MIRACL study.
MedLine Citation:
PMID:  19394618     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To 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. METHODS: We measured plasma t-PA in 2860 of the 3086 (93%) subjects in the MIRACL study, an international randomized trial of atorvastatin 80mg 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. RESULTS: Higher 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. CONCLUSION: In 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.
Scott Kinlay; Gregory G Schwartz; Anders G Olsson; Nader Rifai; Weihang Bao; Peter Libby; Peter Ganz;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial     Date:  2009-03-26
Journal Detail:
Title:  Atherosclerosis     Volume:  206     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-05     Completed Date:  2009-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  551-5     Citation Subset:  IM    
Cardiovascular Division, Veterans Affairs Boston Healthcare System, West Roxbury, MA, United States.
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MeSH Terms
Acute Coronary Syndrome / drug therapy*
Fibrin Fibrinogen Degradation Products
Heptanoic Acids / therapeutic use*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Middle Aged
Pyrroles / therapeutic use*
Tissue Plasminogen Activator / blood*
Reg. No./Substance:
0/Fibrin Fibrinogen Degradation Products; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 0/fibrin fragment D; 110862-48-1/atorvastatin; EC Plasminogen Activator

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