To the Editor: The SYNERGY trial compared enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes. In their article describing the 6-month and 1-year outcomes, Dr Mahaffey and colleagues1 report a result that was not emphasized. As indicated in Figure 2B in their article, there was a statistically significant reduction in the hazard ratio for death or myocardial infarction in the group that consistently received enoxaparin. This benefit persisted for at least 6 months after initial treatment. However, there were no differences between the groups that received enoxaparin followed by unfractionated heparin, or the reverse.
The key to this difference may be that patients treated with enoxaparin reliably and promptly achieved therapeutic levels of anticoagulation. Hull et al2 found that patients who did not attain a therapeutic activated partial thromboplastin time (aPTT) value within 24 hours after initiation of treatment for venous thromboembolic disease were more likely to have a recurrent event. Subsequent venous thromboembolic events occurred less frequently in patients treated with enoxaparin. The relative proportion of patients having another event continued to diverge over 100 days,3 long after the initial phase of unfractionated or low-molecular-weight heparin therapy. The OASIS-2 trial4 had similar findings, with patients who had aPTT values less than 60 seconds in the first 48 hours of treatment having more subsequent cardiovascular events than those whose aPTT values were greater than 60 seconds.
Something critical may be occurring in the first 24 to 48 hours of treatment that determines the likelihood of short- and long-term recurrent events, including death. Mahaffey et al do not specify how many of the patients treated with unfractionated heparin attained a therapeutic level within 24 hours. If a substantial number of these patients had heparin levels that were subtherapeutic, they would have been more likely to have a recurrence than those whose levels were in the therapeutic range.
Financial Disclosures: Dr Schreiber has reported serving as a paid speaker for and receiving honoraria from Sanofi-Aventis.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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