Pulmonary embolism discharge care and long term treatment

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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]

Overview

While hospital admission is necessary for patients who have a massive or submassive pulmonary embolism (PE), patients with low risk PE who have no evidence of hypotension, right ventricular dysfunction, or myocardial necrosis can be discharged early on and put on an outpatient treatment regimen. The long term management of PE depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient. Among non cancer patients, the first line therapy for long term outpatient anticoagulation therapy is vitamin K antagonists (VKA); whereas the first line treatment among cancer patients is low molecular weight heparin (LMWH).

Discharge Care

Discharge Criteria

• The mortality of low risk PE, submassive (intermediate risk) PE, and massive (high risk) PE increases from <3%, to 3-15%, to >15% respectively. Given the elevated rate of mortality in cases of submassive and massive PE, hospital admission is necessary for patients who are stratified within these categories. Hemodynamic stability is not the criteria for discharge. Patients who are hemodynamically stable but have right ventricular dysfunction (stratified as submassive PE), should be admitted.

• Patients with low risk PE who have no evidence of hypotension, right ventricular dysfunction, or myocardial necrosis can be discharged early on and put on an outpatient treatment regimen.

Discharge Medications

Initial Anticoagulation Therapy

• Low risk PE patients can have an early discharge and outpatient treatment. For more details about the choices of treatment, click here.

Long Term Anticoagulation Therapy

• The long term management of PE depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient. Among non cancer patients, the first line therapy for long term management of PE is vitamin K antagonists (VKA); whereas the first line treatment among cancer patients is low molecular weight heparin. If long term treatment with VKA is decided, VKA should be started at the same day with heparin allowing for at least 5 days of overlap until the INR is ≥2 for at least 24 hours. Among patients on extended anticoagulation therapy, the risk vs benefits of the anticoagulation therapy should be assessed regularly (for example annually).

Shown below is an algorithm depicting the long term outpatient anticoagulation therapy for patients with PE.

Is this the first episode of PE?

YES

NO

Is PE provoked?

What is the risk of bleeding?

Yes, transient reversible risk factor

Yes, cancer

No (unprovoked)

Low or moderate

High

Therapy for 3 months ❑ VKA (first line) OR ❑ LMWH OR ❑ Dabigatran OR ❑ Rivaroxaban

Extended therapy or until cancer is cured ❑ LMWH (first line) OR ❑ VKA OR ❑ Dabigatran OR ❑ Rivaroxaban

Therapy for ≥ 3 months ❑ VKA (first line) OR ❑ LMWH OR ❑ Dabigatran OR ❑ Rivaroxaban

Extended therapy ❑ VKA (first line) OR ❑ LMWH OR ❑ Dabigatran OR ❑ Rivaroxaban

Therapy for 3 months ❑ VKA (first line) OR ❑ LMWH OR ❑ Dabigatran OR ❑ Rivaroxaban

Re-assess the risk of bleeding

Low or moderate

High

Extended therapy

Do not extend the therapy beyond the initial 3 months

Note that edoxaban has been evaluated for the treatment of VTE and is currently seeking approval for this indication.

• After treatment in the hospital, the patient should continue anticoagulation therapy for 3 months if the PE is provoked by surgery or a nonsurgical transient risk factor.
• An abnormal D-dimer level at the end of the treatment course might signal the need for continued treatment with anticoagulation for a first time unprovoked pulmonary embolus.
• Long-term treatment is usually recommended with vitamin K antagonists like warfarin, unless warfarin is contraindicated or in cases of cancer or pregnancy..
• The recommended therapeutic INR range for patients with PE is 2.0-3.0.
• Continued warfarin administration needs close monitoring. The patient should have an appointment with the "anticoagulation clinic" before leaving the hospital.

Extended Anticoagulation

Extended treatment means extending the anticoagulation therapy beyond the first 3 months. It is recommended in the following scenarios:

• Unprovoked PE: The patient's risk for recurrent PE should be re-evaluated at 3 months to consider whether or not extended therapy is warranted.
• Active cancer
• Recurrent venous thromboembolism
• Chronic thrombembolic pulmonary hypertension
• For extended therapy, the continued need for anticoagulation and the risk-benefit ratio should be re-evaluated at periodic intervals (eg, annually).
• Patients with recurrent thromboembolic disease, with or without anticoagulation, should be evaluated for possible thrombophilias.

Specific Circumstances

• Malignancy: Low molecular weight heparin is favored over warfarin based on the results of the CLOT trial.
• Pregnancy: Low molecular weight heparin is preferred to avoid the known teratogenic effects of warfarin.
• Asymptomatic patients who are diagnosed with an incidental PE should be managed with the same criteria as those with symptomatic PE.

Newer Anticoagulants

• Dabigatran (direct thrombin inhibitor), Rivaroxaban (Factor Xa inhibitor), and other drugs in the same classes, provide an alternate option to warfarin/LMWH for treatment of PE.
• Advantages include the availability of an oral formulation, no frequent monitoring requirement, a predictable effect profile, and few (known) drug interactions.
• Disadvantages include the currently limited prospective trial data, the theoretical interaction with statins (as they are metabolized by the same CYP3A4 enzyme), and the risk of bleeding.