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Christina Christersson, Jonas Oldgren, Anders Bylock, Agneta Siegbahn, Lars Wallentin, Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemic events: observations from the ESTEEM: reply, European Heart Journal, Volume 28, Issue 14, July 2007, Page 1783, https://doi.org/10.1093/eurheartj/ehm140
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The ESTEEM trial was a phase II study evaluating the efficacy and safety of treatment with the first available oral direct thrombin inhibitor ximelagatran together with aspirin, when compared with aspirin only, after a recent myocardial infarction.1 In a subgroup of 518 (out of 1883) patients, we measured markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer, in serial samples obtained during and after study treatment. Ximelagatran persistently decreased these markers of thrombin generation and fibrin turnover. At follow-up after cessation of study treatment, the levels of coagulation activity in the ximelagatran group had increased and were no longer different from the aspirin only group, although the levels of D-dimer in the ximelagatran group were slightly but significantly lower than those at randomization.2
As pointed out in the letter by Testa and co-workers, the aim of the recently published results from the ESTEEM substudy was to evaluate whether the coagulation activity was related to clinical outcome.3 We found that early reduction of initially high coagulation activity, as measured by the D-dimer levels, identified patients with decreased risk of the composite of death, myocardial re-infarction, severe recurrent ischaemia, or stroke (9 vs. 16%, P = 0.03), regardless of whether the reduction occurred spontaneously or was induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.