Relationship of Activated Partial Thromboplastin Time to Coronary Events and Bleeding in Patients With Acute Coronary Syndromes Who Receive Heparin

BACKGROUND: Antithrombotic therapy with intravenous heparin in conjunction with aspirin reduces negative cardiovascular (CV) outcomes in patients with acute coronary syndromes. The need for a therapeutic range with the activated partial thromboplastin time (APTT) has not been validated in patients with arterial thrombosis who receive heparin. Therefore, it is unclear whether there is an association between recurrent CV events and low APTT values and between bleeding and high APTT values. METHODS AND RESULTS: We examined the relationship between the APTT and recurrent cardiovascular events and bleeding among 5058 patients with an acute coronary syndrome without ST elevation who received intravenous heparin in the OASIS-2 trial. The increase in relative risk of recurrent CV events was 1.54 (95% CI 1.10 to 2.15; P=0.01) among patients with APTT values <60 seconds compared with patients with APTT values > or =60 seconds. When patients had persistently subtherapeutic APTT values for more than 48 hours, the increase in relative risk of a recurrent CV event was 1.84 (95% CI 1.25 to 2.70). Higher APTT values were associated with bleeding; for every 10-second increase in the APTT, the probability of major bleeding was increased by 7% (95% CI 3% to 11%; P=0.0004). CONCLUSIONS: In patients with acute coronary syndromes without ST elevation who are treated with intravenous heparin, our findings justify regular APTT monitoring to minimize recurrent ischemic events and bleeding.