What are the goals of treatment of VTE?  The first goal is to treat the acute event – ie, reduce pain and alleviate the swelling – to make the patient comfortable.  Beyond this, physicians should try to prevent complications such as pulmonary embolism (or fatal PE) and long term sequelae, such as chronic pulmonary hypertension (which may also include the post thrombotic syndrome); ultimately we want to prevent recurrent VTE in the long term.  

In her presentation for this American Journal of Medicine multimedia publication, Dr Hylek views the overall approaches to management of VTE and how the data from the randomized clinical trials apply at the bedside and in the clinic.  In this review I present 

• the data on low molecular weight heparin (LMWH) for initial treatment;

• the data on warfarin; 

• the most recent data on the new, novel oral anticoagulant agents (NOACs). 

The evidence for the efficacy of unfractionated heparin (UFH) comes from small, very old studies that convincingly showed that giving heparin compared with no heparin not only reduced recurrence, but also reduced mortality, of VTE, and thus for many years UFH was the “standard of care.”

In the mid-1980s, LMWH was introduced. LMWH has the same advantages as UFH in that it does not require intravenous administration, it is given in fixed weight-adjusted doses without routine monitoring, and meta-analysis data have demonstrated that LMWH is at least as effective and as safe as UFH.  The most recent meta-analysis, published in 2010[3] even found an advantage for LMWH over UFH, with a reduction in recurrent events, major bleeding, and in overall mortality (Figure 5).  As a result, LMWH has largely replaced UFH .

UFH has not lost its role entirely, however, because it retains the advantage of non-renal clearance, and thus in a hospital setting (eg, the emergency room and the intensive care unit), intravenous UFH remains the treatment of choice for the initial treatment of DVT or PE in many patients.  

Although not shown in Figure 5, there has been an advance over LMWH and UFH with the introduction of an additional parenteral agent, fondaparinux, which is also effective and safe and one of the first designer drugs to be introduced.  However, fondaparinux still has to be given by injection and it is still dependent on renal function for clearance.  Its particular advantage is its possible use in the small niche of patients who are at risk for heparin-induced thrombocytopenia (HIT), because fondaparinux by and large does not induce the formation of antibodies that cause immune HIT.  Eikelboom J. Am J Med 2013; published on-line at http://education.amjmed.com/00000.