Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE. Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited. For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.
Pulmonary embolism (PE) is a serious and costly disease for patients and healthcare systems. Guidelines emphasise the importance of differentiating between patients who are at high risk of mortality (those with shock and/or hypotension), who may be candidates for thrombolytic therapy or surgery, and those with less severe presentations. Recent clinical studies and guidelines have focused particularly on risk stratification of intermediate-risk patients. Although the use of thrombolysis has been investigated in these patients, anticoagulation remains the standard treatment approach. Individual risk stratification directs initial treatment. Rates of recurrence differ between subgroups of patients with PE; therefore, a reviewof provoking factors, along with the risks of morbidity and bleeding, guides the duration of ongoing anticoagulation. The direct oral anticoagulants have shown similar efficacy and, in some cases, reduced major bleeding compared with standard approaches for acute treatment. They also offer the potential to reduce the burden on patients and outpatient services in the post-hospital phase. Rivaroxaban, dabigatran and apixaban have been shown to reduce the risk of recurrent venous thromboembolism versus placebo, when given for >12 months. Patients receiving direct oral anticoagulants do not require regular coagulation monitoring, but follow-up, ideally in a specialist PE clinic in consultation with primary care providers, is recommended.