Low-molecular-weight heparins : mechanisms, trials, and role in contemporary interventional medicine

The clinical spectrum of acute coronary syndromes (ACS) encompasses unstable angina, non-ST-elevation, and ST-elevation myocardial infarction (STEMI). Within an atherosclerotic plaque, disruption of the endothelium can lead to exposure of tissue factor, with platelet adhesion, activation and aggregation, along with activation of the coagulation cascade, culminating in thrombin formation and the development of a cross-linked fibrin clot at the site of injury. Therapy aimed at blocking thrombin formation is now an integral part of the current cardiovascular guidelines in the treatment of ACS. Although unfractionated heparin (UFH) has been the mainstay of antithrombin therapy in the past, it has numerous clinical and biochemical limitations, including substantial protein binding (leading to inconsistent bioavailability), a need for frequent monitoring and adjustment, unreliable and variable degrees of anticoagulation, significant platelet activation, risk of heparin-induced thrombocytopenia, and the inability to block clot bound thrombin. With all of these limitations of UFH, low-molecular-weight heparins (LMWHs) have emerged as attractive alternatives. This review discusses the mechanism of action of LMWHs, and summarizes available literature concerning the use of LMWHs in a variety of clinical settings. Included in this review is an analysis of both current and prior data showing LMWH is as effective as UFH in the conservative and invasive management of patients with ACS. As well, very recent data are evaluated showing the safety and efficacy of LMWHs used in patients transitioning to the cardiac catheterization laboratory, and in those patients undergoing elective or urgent percutaneous coronary intervention (PCI). We also appraise the literature, along with the very recent studies investigating the use of LMWHs as adjunctive therapy to fibrinolytics in patients with STEMI. Finally, we set forth real-world conclusions concerning the use of LMWHs in contemporary interventional practice, including elective PCI and the treatment of ischemic coronary artery disease in the context of rapid invasive management of ACS.