Unfractionated Heparin in Cardiology: Redefining the Standard of Practice

Acute coronary syndromes (ACS) consist of unstable angina (UA), non-ST-segment myocardial infarction (NSTEMI) and ST-segment myocardial infarction (STEMI). Timely intervention with effective, predictable antithrombin therapy is critically important in the early management of these conditions. Platelet aggregation is also an important component of thrombus formation in arterial thrombosis. Historically, unfractionated heparin (UFH) has been combined with aspirin to suppress thrombin propagation and fibrin formation; however, its effectiveness has been questioned in this setting. Unlike newer anticoagulant alternatives, UFH paradoxically stimulates platelet aggregation, which may further promote clot formation. In addition, obtaining a valid therapeutic activated partial thromboplastin time (aPTT) in cardiology patients is a major challenge, and dosing is complex. Due to substantial variation in reagents and instruments, target aPTT ranges for UFH in ACS clinical trials cannot be extrapolated to individual institutions. Further, the risk of ischemic events is greater shortly after abrupt discontinuation of UFH compared with alternative agents with longer half-lives and less stimulation of platelet aggregation. Key UA-NSTEMI clinical trials have demonstrated that UFH is inferior to newer agents, such as the low-molecular-weight heparins (LMWHs). Consistent with this evidence, the most recent practice guidelines of the American College of Cardiology and the American Heart Association in UA-NSTEMI identify the LMWH enoxaparin as the agent of choice. In patients with STEMI receiving the fibrinolytic tenecteplase as reperfusion therapy, enoxaparin has also been superior to UFH in combination. In percutaneous procedures, newer indirect (enoxaparin) and direct (bivalirudin) antithrombins have demonstrated safety and efficacy. There is little doubt that as we move forward in optimizing adjunctive anticoagulation in the cardiology setting, UFH will largely be replaced by better antithrombin agents.