To the Editor: The guidelines for managing acute coronary syndromes, published in a supplement to the Journal in 2006, provide a readily accessible tool for clinicians to enhance patient care.1 However, unfortunately the recommendations concerning adjunctive anticoagulation in patients with acute coronary syndromes (ACS) are suboptimal.

The 2006 guidelines recommend that high-risk patients with non-ST-segment-elevation ACS should be treated with aggressive medical management, including unfractionated heparin or the low molecular weight heparin (LMWH) enoxaparin, based on evidence from randomised trials showing that these agents reduce the risk of non-fatal myocardial infarction (MI).1 However, neither unfractionated heparin nor enoxaparin have been shown to reduce mortality in patients with non-ST-segment-elevation ACS, even when compared against placebo, and enoxaparin increases the risk of bleeding when compared with unfractionated heparin.2-4 By contrast, the OASIS-5 study, presented at the European Society of Cardiology Meeting in September 2005 and published in early 2006, showed that fondaparinux (a pentasaccharide inhibitor of factor Xa) compared with enoxaparin reduced death and stroke rates, and reduced the risk of bleeding by one half.5 Updating the recommendation so that enoxaparin was replaced with fondaparinux for patients with non-ST-segment-elevation ACS would save six Australian lives at 30 days for every 1000 patients treated, and would cause 19 fewer bleeds.

The recommendations of the 2006 ACS guidelines concerning the management of patients with ST-segment-elevation MI are similarly suboptimal. There are now convincing data from randomised trials that enoxaparin is more effective than unfractionated heparin for preventing recurrent MI in patients with ST-segment-elevation MI who have been treated with fibrinolytic therapy.4,6 However, as in the case with non-ST-segment-elevation ACS, enoxaparin has never been shown to reduce mortality in ST-segment-elevation MI. By contrast, both the LMWH reviparin, and fondaparinux, reduce mortality,7,8 and fondaparinux does so without increasing the risk of bleeding.8

We appreciate that rapid advances in the management of ACS make it increasingly difficult for evidence-based guidelines to reflect the best evidence from clinical trials. However, when new evidence becomes available that is clinically relevant at the individual and population level, we believe the guidelines working group and the Journal have a responsibility to update the readers.

In reply: We thank Eikelboom et al for presenting new data on acute coronary syndrome (ACS) management. In this field of rapid advances, another recent study, ACUITY, has also been published, which examined bivalirudin in ACS.1 The Australian guidelines2 are based on peer reviewed published reports, and neither OASIS-53 nor ACUITY1 were released at the conclusion of the formulation of the guidelines. Also, fondaparinux is only available on the Pharmaceutical Benefits Scheme (PBS) in Australia for thromboembolic prophylaxis, and bivalirudin is currently only approved by the PBS for therapy during percutaneous coronary interventions.

The Australian guidelines are consistent with international guidelines for both unfractionated heparin and low molecular weight heparin considered as Grade A recommendations for treating non-ST-segment-elevation ACS, based on Level 1 evidence (American College of Cardiology/American Heart Association guidelines). For example, the FRISC trial showed a significant reduction in mortality and myocardial infarction with dalteparin (compared with placebo; 1.8% v 4.8%; P = 0.001) at 6 days, which persisted at 40 days.4

The Australian ACS guidelines are a living document, and new evidence, such as the OASIS-5 (fondaparinux)3 and ACUITY (bivalirudin)1 findings, will be considered on their relative merits in future updates of the guidelines (available on the National Heart Foundation Australia website at http://www.heartfoundation.com.au).