Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), continues to be a major cause of morbidity and mortality among hospitalized patients. Although it is well-known that anticoagulation therapy is effective in the prevention and treatment of VTE events, these agents are some of the highest-risk medications a hospitalist will prescribe given the danger of major bleeding. With the recent approval of several newer anticoagulants, it is important for the practicing hospitalist to be comfortable initiating, maintaining, and stopping these agents in a wide variety of patient populations.
In February 2016, an update to the ninth edition of the antithrombotic guideline from the American College of Chest Physician (ACCP) was published and included updated recommendations on 12 topics in addition to three new topics. This 10th-edition guideline update is referred to as AT10.1
One of the most notable changes in the updated guideline is the recommended choice of anticoagulant in patients with acute DVT or PE without cancer. Now, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, or edoxaban are recommended over warfarin. Although this is a weak recommendation based on moderate-quality evidence (grade 2B), this is the first time that warfarin is not considered first-line therapy. It should be emphasized that none of the four FDA-approved DOACs are preferred over another, and they should be avoided in patients who are pregnant or have severe renal disease. In patients with DVT or PE and cancer, low-molecular-weight heparin (LMWH) is still the preferred medication. If LMWH is not prescribed, AT10 does not have a preference for either a DOAC or warfarin for patients with cancer.
When it comes to duration of anticoagulation following a VTE event, the updated guideline continues to recommend three months for a provoked VTE event, with consideration for lifelong anticoagulation for an unprovoked event for patients at low or moderate bleeding risk. However, it now suggests that the recurrence risk factors of male sex and a positive D-dimer measured one month after stopping anticoagulant therapy should be taken into consideration when deciding whether extended anticoagulation is indicated.
AT10 also includes new recommendations concerning the role of aspirin for extended VTE treatment. Interestingly, the 2008 ACCP guideline gave a strong recommendation against the use of aspirin for VTE management in any patient population. In the 2012 guideline, the role of aspirin was not addressed for VTE treatment. Now, AT10 states that low-dose aspirin can be used in patients who stop anticoagulant therapy for treatment of an unprovoked proximal DVT or PE as an extended therapy (grade 2B). The significant change in this recommendation stems from two recent randomized trials that compared aspirin with placebo for the prevention of VTE recurrence in patients who have completed a course of anticoagulation for a first unprovoked proximal DVT or PE.2,3 Although the guideline doesn’t consider aspirin to be a reasonable alternative to anticoagulation for patients who require extended therapy and are agreeable to continue, for patients who have decided to stop anticoagulation, aspirin appears to reduce recurrent VTE by approximately one-third, with no significant increased risk of bleeding.
Another significant change in AT10 is the recommendation against the routine use of compression stockings to prevent postthrombotic syndrome (PTS). This change was influenced by a recent multicenter randomized trial showing that elastic compression stockings did not prevent PTS after an acute proximal DVT.4 The guideline authors remark that this recommendation focuses on the prevention of the chronic complications of PTS rather than treatment of the symptoms. Thus, for patients with acute or chronic leg pain or swelling from DVT, compression stockings may be justified.
A topic that was not addressed in the previous guideline was whether patients with a subsegmental PE should be treated. The guideline now suggests that patients with only subsegmental PE and no ultrasound-proven proximal DVT of the legs should undergo “clinical surveillance” rather than anticoagulation (grade 2C). Exceptions include patients at high risk for recurrent VTE (e.g., hospitalization, reduced mobility, active cancer, or irreversible VTE risk factors) and those with a low cardiopulmonary reserve or marked symptoms thought to be from PE. AT10 also states that patient preferences regarding anticoagulation treatment as well as the patient’s risk of bleeding should be taken into consideration. If the decision is made to not prescribe anticoagulation for subsegmental PE, patients should be advised to seek reevaluation if their symptoms persist or worsen.
The 2012 guideline included a new recommendation that patients with low-risk PE (typically defined by a low Pulmonary Embolism Severity Index [PESI] score) could be discharged “early” from the hospital. This recommendation has now been modified to state that patients with low-risk PE may be treated entirely at home. It is worth noting that outpatient management of low-risk PE has become much less complicated if using a DOAC, particularly rivaroxaban and apixaban as neither require initial treatment with parenteral anticoagulation.
AT10 has not changed the recommendation for which patients should receive thrombolytic therapy for treatment of PE. It recommends systemic thrombolytic therapy for patients with acute PE associated with hypotension (defined as systolic blood pressure less than 90 mmHg for 15 minutes) who are not at high risk for bleeding (grade 2B). Likewise, for patients with acute PE not associated with hypotension, the guideline recommends against systemic thrombolytics (grade 1B). If thrombolytics are implemented, AT10 favors systemic administration over catheter-directed thrombolysis (CDT) due to the higher-quality evidence available. However, the authors state that CDT may be preferred for patients at higher risk of bleeding and when local expertise is available. Lastly, catheter-assisted thrombus removal should be considered in patients with acute PE and hypotension who have a high bleeding risk, who have failed systemic thrombolytics, or who are in shock and likely to die before systemic thrombolytics become therapeutic.
Although no prospective trials have evaluated the management of patients with recurrent VTE events while on anticoagulation therapy, AT10 offers some guidance. After ensuring the patient truly had a recurrent VTE event while on therapeutic warfarin or compliant with a DOAC, the authors suggest switching to LMWH for at least one month (grade 2C). Furthermore, for patients who have a recurrent VTE event while compliant on long-term LMWH, the guideline suggests increasing the dose of LMWH by about one-quarter to one-third (grade 2C).
It is important to note that of the 54 recommendations included in the complete guideline update, only 20 were strong recommendations (grade 1), and none were based on high-quality evidence (level A). It is obvious that more research is needed in this field. Regardless, the ACCP antithrombotic guideline remains the authoritative source in VTE management and has a strong influence on practice behavior. With the recent addition of several newer anticoagulants, AT10 is particularly useful in helping providers understand when and when not to use them. The authors indicate that future iterations will be continually updated, describing them as “living guidelines.” The format of AT10 was designed to facilitate this method with the goal of having discrete topics discussed as new evidence becomes available.
Hospital Medicine Takeaways
Despite the lack of randomized and prospective clinical trials, the updated recommendations from AT10 provide important information on challenging VTE issues that the hospitalist can apply to most patients most of the time. Important updates include:
- Prescribe DOACs as first-line agents for the treatment of acute VTE in patients without cancer.
- Use aspirin for the prevention of recurrent VTE in patients who stop anticoagulation for treatment of an unprovoked DVT or PE.
- Avoid compression stockings for the sole purpose of preventing postthrombotic syndrome.
- Do not admit patients with low-risk PE (as determined by the PESI score) to the hospital but rather treat them entirely at home.
Lastly, it is important to remember that VTE treatment decisions need to be individualized based on the clinical, imaging, and biochemical features of your patient.
Paul J. Grant, MD, SFHM, is assistant professor of medicine and director of perioperative and consultative medicine within the Department of Internal Medicine at the University of Michigan Health System in Ann Arbor.
- Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.
- Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979-1987.
- Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366(21):1959-1967.
- Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo controlled trial. Lancet. 2014;383(9920):880-888.