Risks of recurrent VTE after stopping anticoagulant therapy which justify strong or weak recommendations to either stop anticoagulants at 3 months or to treat indefinitely.
Calculations based on a 5-year period, with one-third of recurrences in the first year and two-thirds in the next 4 years. Consistent with the Grading of Recommendations Assessment, Development, and Evaluation GRADE nomenclature and the ACCP guidelines, a strong recommendation indicates a high degree of confidence that following the recommendation will result in substantial benefits for most patients. A weak recommendation indicates a lower degree of confidence that following the recommendation will result in substantial benefits for patients, usually because the quality of evidence is poorer, the benefits and risks are more closely balanced, or because differences among patients may shift that balance.
Weak recommendations, therefore, are sensitive to differences in patient values and preferences. Whereas the ACCP guidelines divided patients with VTE provoked by a reversible risk factor into 2 categories provoked by surgery or a nonsurgical trigger , while acknowledging there is a higher risk of recurrence in the later subgroup, we will consider this as a single category.
This is because both subgroups have sufficiently low risks of recurrence to recommend stopping anticoagulants at 3 months strongly for VTE provoked by surgery; weakly for VTE provoked by a nonsurgical trigger if there is a low or intermediate risk of bleeding.
We discourage indefinite therapy if there is a convincing reversible risk factor Table 2. However, if patients are still recovering from the VTE, or if the provoking factor is incompletely resolved, it is appropriate to treat for longer than 3 months.
Patients with a first unprovoked proximal DVT or PE who do not have a high risk of bleeding are expected to derive a modest mortality benefit from extended therapy, resulting in a weak recommendation for indefinite anticoagulation.
However, because these finding are preliminary, it appears equally acceptable to either use, or not use, d -dimer levels to help decide about duration of therapy. If the intention is to use d -dimer testing in this way, it should first be established with the patient that d -dimer results will influence treatment decisions Figure 1.
Patients with VTE who should be treated for 3 months and who should be treated indefinitely. Use of d -dimer testing to guide treatment decisions in patients with a first unprovoked proximal DVT or PE is optional. The predictive value of patient sex and posttreatment d -dimer levels has not been evaluated after a second unprovoked VTE. Patients with VTE and cancer have a high risk of recurrence and are expected to derive substantial benefit from extended anticoagulant therapy strong recommendation, reduced to weak if bleeding risk is high.
If there is uncertainty, our practice is to continue treatment until 6 months have passed without recurrent disease.
In addition to considering the usual contraindications, we avoid using the new oral anticoagulants in patients who are receiving chemotherapy. Some patients resent, whereas others are reassured by, anticoagulant therapy. Consequently, patient preferences should influence decision-making, particularly when there is a weak recommendation for indefinite therapy. Some patients may indicate that they do not want to be involved with decision-making, and care should be taken to avoid adding to the burden of their illness.
Costs ie, to patients, health care systems, third-party payers and available treatment options eg, licensing may further influence decisions at a patient or societal level. It is not known whether the time needed to complete active treatment differs with the type of anticoagulant.
For now, it is reasonable to assume that this is not the case. Because the new oral anticoagulants are less burdensome than VKA and cause less bleeding, more patients with unprovoked VTE are expected to opt for indefinite therapy.
After anticoagulation for unprovoked VTE, aspirin reduces the risk of recurrence by about one-third. Patients who are treated indefinitely should be reviewed regularly eg, annually to ensure that: 1 they have not developed contraindications to anticoagulant therapy; 2 their preferences have not changed; 3 they can avail of improved ways to predict risk of recurrence and the possibility of safely stopping therapy; and 4 they are being treated with the most suitable anticoagulant regimen.
Contribution: C. Conflict-of-interest disclosure: C. Sign In or Create an Account. Sign In. Skip Nav Destination Content Menu. Close Abstract. Patients should either stop anticoagulants when the acute episode of VTE has been adequately treated or remain on treatment indefinitely.
Benefits and risks of indefinite anticoagulant therapy. Which patients should stop anticoagulants at 3 months and which should remain on anticoagulants indefinitely? Risk of recurrent VTE that justifies strong and weak recommendation for either 3 months or indefinite anticoagulation. Duration of anticoagulation in patients with VTE and cancer. Influence of patient preferences and cost. Should duration of treatment be influenced by type of anticoagulant? Antiplatelet therapy. Follow-up of patients on extended therapy.
Article Navigation. Clive Kearon , Clive Kearon. This Site. Google Scholar. Elie A. Akl Elie A. Unprovoked PE means there was no clear risk factor such as recent travel, surgery, or trauma to cause the clot. Having unprovoked PE means there is a higher risk of having another blood clot in the future compared with clots caused by a reversible, temporary risk factor such as a long airplane ride. The study compared the effects of giving blood-thinning medication for 6 months compared with 2 years.
The study looked at how often people in each group had 1 another blood clot and 2 major bleeding as a side effect. The results showed a significantly lower risk of having another blood clot in the group that received the treatment for longer 2 years , without a major increase in bleeding risk.
If you have had a first-time PE without a clear cause, you may benefit from longer treatment with blood thinners than the usual 3 to 6 months. Talk to your doctor about your individual risks and benefits for taking blood thinners vs having another blood clot. Centers for Disease Control and Prevention www. Many are available in English and Spanish. A Patient Page describing how blood thinners work was published in the December 18, , issue; one on DVT was published in the May 26, , issue; and one on PE was published in the February 6, , issue.
Jin J. Treatment Duration for Pulmonary Embolism. Coronavirus Resource Center. However, major or clinically relevant non-major bleeding was increased in patients treated with apixaban 2. After an additional months of therapy, treatment with an extended course of rivaroxaban reduced the incidence of DVT or PE 1. Major or clinically relevant non-major bleeding was significantly higher in the patients treated with rivaroxaban as compared to placebo 6.
In the RE-SONATE trial, patients who had already completed and tolerated months of therapy with an anticoagulant were randomized to either dabigatran mg twice daily or placebo. Major or clinically relevant non-major bleeding was significantly higher in the patients treated with dabigatran as compared to placebo 5. Secondary prevention strategies have also evaluated therapies other than anticoagulants. Taken as a whole, these data support personalizing the treatment strategies for patients with VTE.
In those patients in whom the risk of recurrent VTE is low e. VTE occurred in the setting of indwelling vascular access or patients in whom the risk of bleeding is significant, shorter duration of anticoagulation three months is appropriate.
Dose adjustment may be required for these medications. Direct-acting anticoagulants have shorter half-lives than warfarin, and missed doses or premature discontinuation increases the risk of thrombotic events. Also, because elimination of direct-acting anticoagulants is more dependent on renal function than with warfarin, dose adjustment may be required for patients with chronic kidney disease. Only dabigatran has a commercially available reversal agent, although other reversal agents are in development.
In , the U. Food and Drug Administration approved idarucizumab Praxbind , a monoclonal antibody that binds dabigatran in the serum. For patients experiencing a devastating bleed, such as intracranial hemorrhage, treatment includes stopping the direct-acting anticoagulant; initiating supportive therapy; and administering activated charcoal, antifibrinolytic agents, and prothrombin complex concentrate.
The ACCP recommends the use of direct-acting anticoagulants over warfarin for VTE treatment in patients without cancer weak recommendation based on moderate quality evidence, per the ACCP grading system.
For patients transitioning from one anticoagulant to another, specific recommendations for conversion are available in eTable A and from the U. Apixaban Eliquis : 10 mg twice per day for 7 days, then 5 mg twice per day. Discontinue apixaban and begin both a parenteral anticoagulant and warfarin when the next dose of apixaban is due; discontinue parenteral anticoagulant when INR reaches the target range. From oral or parenteral anticoagulants to apixaban:. Dabigatran Pradaxa : mg twice per day after 5 to 10 days of parenteral anticoagulation.
CrCl 30 to 50 mL per minute per 1. CrCl 15 to 30 mL per minute per 1. From a parenteral anticoagulant to dabigatran:. Edoxaban Savaysa : 60 mg every 24 hours after 5 to 10 days of initial therapy with a parenteral anticoagulant. INR must be measured at least weekly and just before the daily dose of edoxaban to minimize the influence of edoxaban on INR measurements. From continuous infusion of unfractionated heparin to edoxaban:. Discontinue current oral anticoagulant and initiate edoxaban when the next dose of the initial oral anticoagulant is due.
Discontinue edoxaban and start the other oral anti-coagulant when the next dose of edoxaban is due. Rivaroxaban Xarelto : 15 mg twice per day for 21 days, 20 mg once per day should be taken with food. Discontinue rivaroxaban and initiate warfarin and a parenteral anticoagulant when the next dose of rivaroxaban is due. From continuous infusion of unfractionated heparin to rivaroxaban:. Eliquis apixaban —drug summary.
Accessed January 18, Pradaxa dabigatran etexilate mesylate —drug summary. Savaysa edoxaban —drug summary. Xarelto rivaroxaban —drug summary. Because of the high risk of bleeding, thrombolysis is restricted to specific circumstances.
Expert consensus guidelines support thrombolytic therapy in patients with persistent hypotension or shock secondary to acute PE. Thrombolysis is not indicated in hemodynamically stable patients with intermediate-risk PE. Massive proximal lower extremity thrombosis or ilio-femoral thrombosis associated with severe symptoms or limb-threatening ischemia for less than 14 days is the only widely accepted indication for thrombolytic therapy in patients with DVT.
The most appropriate therapy depends on the treatment center's expertise. An inferior vena cava filter is rarely indicated, and evidence for safety and effectiveness is lacking. Its use for other reasons is controversial. The risk of VTE recurrence is greatest in the first year after the event and remains elevated indefinitely compared with the general population.
Long-term anticoagulation reduces the risk of recurrent VTE but results in more bleeding events. Considering this trade-off, it is critical that the duration of anticoagulation therapy be individualized based on the patient's risk of recurrence vs. Risk factors for bleeding are summarized in Table 2. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published correction appears in Chest.
The d -dimer test has been used to stratify risk of recurrent VTE. The d -dimer value is checked one month after anticoagulation ends, with an increased level indicating increased risk. Some conditions, such as pregnancy and cancer, require special consideration when treating VTE.
These special considerations are described in Table 3. For patients with low-risk subsegmental PE without proximal DVT, clinical surveillance is preferred over anticoagulation. Aspirin is generally not considered a reasonable alternative to anticoagulant therapy. If a patient has decided to stop anticoagulants, aspirin can be considered for prevention of recurrent VTE.
Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped when anticoagulants were started.
An evaluation for possible thromboendarterectomy by an experienced team should be considered. In patients with inoperable chronic thromboembolic pulmonary hypertension or persistent pulmonary hypertension after thromboendarterectomy, referral to a team with expertise in the evaluation and management of pulmonary hypertension is generally warranted.
If the patient does not have severe symptoms or risk factors for extension, perform serial imaging of the deep veins for 2 weeks over initial anticoagulation. No anticoagulation is needed if no extension of thrombus is detected.
Anticoagulation should be initiated if DVT extends into the proximal veins. In patients with acute VTE, surgery should be delayed until 3 months of treatment have elapsed, if possible.
Ambulation should be encouraged. Evidence does not support the use of compression stockings for prevention of postthrombotic syndrome. Catheter-directed thrombolysis increases the patency of veins and reduces the incidence of postthrombotic syndrome by one-third. Isolated subsegmental pulmonary embolism may be overdiagnosed because of breathing motion and beam-hardening artifacts.
There is limited evidence to determine the effectiveness and safety of anticoagulation therapy in patients with subsegmental pulmonary embolism. The American College of Chest Physicians guideline states that anticoagulation should not be used in patients with subsegmental pulmonary embolism if they do not have proximal DVT and are at low risk of recurrence.
Patients with superficial venous thrombosis are at higher risk of developing DVT. Consider anticoagulation in extensive cases and in those associated with involvement above the knee, particularly if close to the saphenofemoral junction or the greater saphenous vein; severe symptoms; history of VTE or superficial venous thrombosis; active cancer; or recent surgery.
This is most often associated with a central venous catheter and is treated similarly to lower extremity DVT. Morbidly obese patients are usually excluded from clinical trials of anticoagulants. Data are lacking regarding direct-acting oral anticoagulants.
Heparin can be used in the initial treatment of VTE. Refer to the manufacturer's directions for individual medications because some may recommend a maximum dose despite patient weight.
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