Creatine Kinase is Associated with Bleeding after Myocardial Infarction

Background Highly elevated plasma activity of the ADP scavenging enzyme creatine kinase (CK) might reduce ADP and ADP-dependent platelet activation. Therefore, we studied, whether high CK after myocardial infarction (MI) is associated with bleeding. Methods Data of the Thrombolysis In Myocardial Infarction Study Group phase II trial on the efficacy of angioplasty following intravenous recombinant tissue-type plasminogen activator (rt-PA), are used to assess whether peak plasma CK (CKmax) is independently associated with adjudicated fatal or non-fatal bleeding (primary) and combined bleeding/all-cause mortality (secondary) in multivariable binomial logistic regression analysis, adjusting for baseline and treatment allocation covariates. Results The included patients (N=3339, 82% men, 88% white, mean age 57 y, SE 0.2), had a history of angina pectoris (55%), hypertension (38%), and/or diabetes mellitus (13%). CKmax ranged between 16 and 55 890 IU/L (mean 2389 IU/L; SE 41), reached within 8 h in 51% of the patients (93% within 24 h). Adjudicated fatal/non-fatal bleeding occurred in 30% of the patients (respectively 26% in the low vs 34% in the high CK tertile), and bleeding/all-cause mortality in 35% (29% in the low, vs 40% in the high CK tertile). The adjusted odds ratio for fatal/non-fatal bleeding (vs not bleeding and survival) was 2.6 [95% CI, 1.8 to 3.7]/log CKmax increase, and 3.1 [2.2 to 4.4] for bleeding/all-cause mortality). Conclusion Highly elevated plasma CK after MI might be a hitherto overlooked independent indicator of bleeding and hemorrhagic death. This biologically plausible association warrants prospective study of the potential role of CK in hemorrhagic diathesis, and the risk of severe, potentially fatal bleeding with antithrombotic or thrombolytic therapy in the presence of high plasma CK. ClinicalTrials.gov identifier (NCT number) NCT00000505