CHEST 2016-Antithrombotic Therapy for VTE Disease

Question 1

Recommended length of anticoagulant therapy for proximal DVT or pulmonary embolism

Answer 1

Recommend long-term (3 months) anticoagulant therapy over no such therapy (Grade 1B).

Question 2

Reasons (4) for choosing VKA over LMWH for VTE in patients WITHOUT cancer

Answer 2

1. injections are burdensome
2. LMWH is expensive
3. there are low rates of recurrence with VKA in patients with VTE without cancer
4. VKA may be as effective as LMWH in patients without cancer.

Question 3

Reasons (4) for choosing LMWH over VKA for VTE in patients WITH cancer

Answer 3

1. More effective than VKA in cancer
2. Less recurrence of VTE in patients with cancer
3. More reliable dosing than orals for patients with vomiting
4. Easier to hold/adjust dose if interventions or thrombocytopenia develops
5. there is moderate-quality evidence that LMWH was more effective than VKA in patients with cancer
6. there is a substantial rate of recurrent VTE in patients with VTE and cancer who are treated with VKA
7. it is often harder to keep patients with cancer who are on VKA in the therapeutic range
8. LMWH is reliable in patients who have difficulty with oral therapy (eg, vomiting)
9. LMWH is easier to withhold or adjust than VKA if invasive interventions are required or thrombocytopenia develops

Question 4

Recommended anticoagulants for proximal DVT or PE in patients WITHOUT cancer

Answer 4

NOAC > VKA > LMWH

In patients with DVT of the leg or PE and no cancer, as long-term (first 3 months) anticoagulant therapy, we suggest dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonist (VKA) therapy (all Grade 2B).

There is no preference for one NOAC over the others.

For patients with DVT of the leg or PE and no cancer who are not treated with dabigatran, rivaroxaban, apixaban, or edoxaban, we suggest VKA therapy over LMWH (Grade 2C).

Question 5

Recommended anticoagulants for proximal DVT or PE in patients WITH cancer

Answer 5

LMWH > VKA = NOAC

We still suggest LMWH over VKA in patients with cancer. In patients with VTE and cancer who are not treated with LMWH, we do not have a preference for either an NOAC or VKA.

Question 6

Does the anticoagulant agent need to be changed after the first 3 months of therapy (if the patient needs to continue therapy?)

Answer 6

No.

In patients with DVT of the leg or PE who receive extended therapy, we suggest that there is no need to change the choice of anticoagulant after the first 3 months (Grade 2C).

It may be appropriate for the choice of anticoagulant to change in response to changes in the patient’s circumstances or preferences during the long-term or extended phases of treatment.

Question 7

What is the recommended duration of therapy for proximal DVT or PE provoked by surgery?

Answer 7

In patients with a proximal DVT of the leg or PE provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B), (ii) treatment of a longer, time-limited period (eg, 6, 12, or 24 months) (Grade 1B), or (iii) extended therapy (no scheduled stop date) (Grade 1B).

Question 8

What is the recommended duration of therapy for proximal DVT or PE provoked by a nonsurgical transient factor?

Answer 8

3 months

In patients with a proximal DVT of the leg or PE provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B) and (ii) treatment of a longer time-limited period (eg, 6, 12, or 24 months) (Grade 1B).

We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B), and recommend treatment for 3 months over extended therapy if there is a high risk of bleeding (Grade 1B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

Question 9

Duration of therapy for isolated distal DVT of leg provoked by surgery or nonsurgical transient risk factor (if being treated with anticoagulation)?

Answer 9

3 months

In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor, we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Grade 2C); we recommend treatment with anticoagulation for 3 months over treatment of a longer, time-limited period (eg, 6, 12, or 24 months) (Grade 1B); and we recommend treatment with anticoagulation for 3 months over extended therapy (no scheduled stop date) (Grade 1B). Remarks: Duration of treatment of patients with isolated distal DVT refers to patients in whom a decision has been made to treat with anticoagulant therapy; however, it is anticipated that not all patients who are diagnosed with isolated distal DVT will be prescribed anticoagulants.

Question 10

Duration of therapy for UNPROVOKED DVT (either isolated distal or proximal) or UNPROVOKED PE?

Answer 10

At least 3 months

In patients with an unprovoked DVT of the leg (isolated distal or proximal) or PE, we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B), and we recommend treatment with anticoagulation for 3 months over treatment of a longer, time-limited period (eg, 6, 12, or 24 months) (Grade 1B). Remarks: After 3 months of treatment, patients with unprovoked DVT of the leg or PE should be evaluated for the risk-benefit ratio of extended therapy. Duration of treatment of patients with isolated distal DVT refers to patients in whom a decision has been made to treat with anticoagulant therapy; however, it is anticipated that not all patients who are diagnosed with isolated distal DVT will be prescribed anticoagulants.

Question 11

Duration of therapy for FIRST UNPROVOKED PROXIMAL DVT OR PE and low/moderate bleed risk? What about if high bleed risk?

Answer 11

Extended duration (no stop date) if low/mod bleed risk,
3 months if high bleed risk

In patients with a first VTE that is an unprovoked proximal DVT of the leg or PE and who have a (i) low or moderate bleeding risk (see text), we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B), and a (ii) high bleeding risk (see text), we recommend 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 1B). Remarks: Patient sex and D-dimer level measured a month after stopping anticoagulant therapy may influence the decision to stop or extend anticoagulant therapy (see text). In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

Question 12

Duration of therapy for SECOND UNPROVOKED VTE and low/moderate bleed risk? Duration for high bleed risk?

Answer 12

Extended duration (no stop date) for low/mod bleed risk, 3 months for high bleed risk

In patients with a second unprovoked VTE and who have a (i) low bleeding risk (see text), we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months (Grade 1B); (ii) moderate bleeding risk (see text), we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B); or (iii) high bleeding risk (see text), we suggest 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 2B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

Question 13

Duration of therapy for DVT of leg or PE and active cancer (aka cancer-associated thrombosis) and low/mod bleed risk? Duration for high bleed risk?

Answer 13

Extended duration (no stop date) for low/mod bleed risk is recommended. 
Extended duration (no stop date) for high bleed risk is SUGGESTED.

In patients with DVT of the leg or PE and active cancer (“cancer-associated thrombosis”) and who (i) do not have a high bleeding risk, we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 1B), and (ii) have a high bleeding risk, we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B). Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

Question 14

If a patient with an UNPROVOKED PROXIMAL DVT OR PE and is stopping anticoagulation therapy, is aspirin a reasonable alternative to prevent recurrent VTE?

Answer 14

No. It is not recommended as an alternative to anticoagulants, BUT IT IS SUGGESTED OVER NO ASPIRIN.

In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE (Grade 2B). Remarks: Because aspirin is expected to be much less effective at preventing recurrent VTE than anticoagulants, we do not consider aspirin a reasonable alternative to anticoagulant therapy in patients who want extended therapy. However, if a patient has decided to stop anticoagulants, prevention of recurrent VTE is one of the benefits of aspirin that needs to be balanced against aspirin’s risk of bleeding and inconvenience. Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped when anticoagulants were started.

Question 15

When is serial imaging suggested over anticoagulation for acute isolated distal DVT of the leg? How long should serial imaging occur?

Answer 15

If pt is without severe symptoms or risk factors for extension, conduct serial imaging of deep veins for 2 weeks

In patients with acute isolated distal DVT of the leg and (i) without severe symptoms or risk factors for extension (see text), we suggest serial imaging of the deep veins for 2 weeks over anticoagulation (Grade 2C), and (ii) with severe symptoms or risk factors for extension (see text), we suggest anticoagulation over serial imaging of the deep veins (Grade 2C). Remarks: Patients at high risk for bleeding are more likely to benefit from serial imaging. Patients who place a high value on avoiding the inconvenience of repeat imaging and a low value on the inconvenience of treatment and on the potential for bleeding are likely to choose initial anticoagulation over serial imaging.

Question 16

Does treatment differ for acute isolated DVT vs. acute proximal DVT?

Answer 16

NO

In patients with acute, isolated, distal DVT of the leg who are managed with anticoagulation, we recommend using the same anticoagulation as for patients with acute proximal DVT (Grade 1B).

Question 17

If conducting serial imaging, how do you know when to anticoagulate an acute isolated distal DVT of the leg?

Answer 17

No extension–don’t anticoagulate

Extension but remains in distal veins–anticoag is SUGGESTED

Extension into proximal veins–anticoag is RECOMMENDED

In patients with acute, isolated, distal DVT of the leg who are managed with serial imaging, we (i) recommend no anticoagulation if the thrombus does not extend (Grade 1B), (ii) suggest anticoagulation if the thrombus extends but remains confined to the distal veins (Grade 2C), and (iii) recommend anticoagulation if the thrombus extends into the proximal veins (Grade 1B).

Question 18

Who would tend to choose catheter-directed thrombolysis (CDT) over anticoagulation for an acute proximal DVT?

Answer 18

Those who prefer prevention of PTS over the cost, complexity, or risk of bleed with CDT

In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C). Remarks: Patients who are most likely to benefit from CDT (see text), who attach a high value to prevention of PTS, and a lower value to the initial complexity, cost, and risk of bleeding with CDT, are likely to choose CDT over anticoagulation alone.

Question 19

Is an IVC filter recommended for acute DVT/PE already treated with anticoagulants?

Answer 19

No

In patients with acute DVT or PE who are treated with anticoagulants, we recommend against the use of an IVC filter (Grade 1B).

Question 20

Should you use compression stockings to prevent PTS?

Answer 20

Routine use is not suggested to prevent PTS, but it is justified to use to manage acute or chronic symptoms.

Basically: symptoms–use stockings, no symptoms–don’t use stockings

In patients with acute DVT of the leg, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). Remarks: This recommendation focuses on prevention of the chronic complication of PTS and not on the treatment of symptoms. For patients with acute or chronic symptoms, a trial of graduated compression stockings is often justified.

Question 21

When should you anticoagulate a subsegmental PE (no involvement of proximal pulmonary arteries) if there is no proximal DVT in the legs?

Answer 21

Anticoagulate if high-risk for recurrent VTE. Otherwise, use clinical surveillance.

In patients with subsegmental PE (no involvement of more proximal pulmonary arteries) and no proximal DVT in the legs who have a (i) low risk for recurrent VTE (see text), we suggest clinical surveillance over anticoagulation (Grade 2C), and (ii) high risk for recurrent VTE (see text), we suggest anticoagulation over clinical surveillance (Grade 2C). Remarks: US imaging of the deep veins of both legs should be done to exclude proximal DVT. Clinical surveillance can be supplemented by serial US imaging of the proximal deep veins of both legs to detect evolving DVT (see text). Patients and physicians are more likely to opt for clinical surveillance over anticoagulation if there is good cardiopulmonary reserve or a high risk of bleeding.

Question 22

When is it ok to discharge a patient home early (before 5 days of hospital treatment)?

Answer 22

If patient has low-risk PE and adequate home circumstances (ie ED Treat and Street)

In patients with low-risk PE and whose home circumstances are adequate, we suggest treatment at home or early discharge over standard discharge (eg, after the first 5 days of treatment) (Grade 2B).

Question 23

When is it recommended to use systemic thrombolytic therapy for PE?

Answer 23

For acute PE with hypotension and low bleed risk

In patients with acute PE associated with hypotension (eg, systolic BP < 90 mm Hg) who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2B).

In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (Grade 1B).

Question 24

When is it suggested to use systemic thrombolytic therapy if the patient has already started anticoagulant therapy?

Answer 24

In a patient with acute PE who develops cardiopulmonary deterioration or hypotension after starting anticoag but has low bleed risk

In selected patients with acute PE who deteriorate after starting anticoagulant therapy but have yet to develop hypotension and who have a low bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2C).

Remarks: Patients with PE and without hypotension who have severe symptoms or marked cardiopulmonary impairment should be monitored closely for deterioration. Development of hypotension suggests that thrombolytic therapy has become indicated. Cardiopulmonary deterioration (eg, symptoms, vital signs, tissue perfusion, gas exchange, cardiac biomarkers) that has not progressed to hypotension may also alter the risk-benefit assessment in favor of thrombolytic therapy in patients initially treated with anticoagulation alone.

Question 25

Which type of thrombolytic therapy is suggested for acute PE: systemic therapy using peripheral vein, or CDT?

Answer 25

Systemic thrombolytic via peripheral vein over CDT.

In patients with acute PE who are treated with a thrombolytic agent, we suggest systemic thrombolytic therapy using a peripheral vein over CDT (Grade 2C). Remarks: Patients who have a higher risk of bleeding with systemic thrombolytic therapy, and who have access to the expertise and resources required to do CDT, are likely to choose CDT over systemic thrombolytic therapy.

Question 26

When should you use catheter-assisted thrombus REMOVAL?

Answer 26

For acute PE with hypotension and: high bleed risk, failed systemic thrombolysis, or shock than can potentially cause death within hours (before systemic thrombolytic can take effect)

In patients with acute PE associated with hypotension and who have (i) a high bleeding risk, (ii) failed systemic thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention (Grade 2C).

Remarks: Catheter-assisted thrombus removal refers to mechanical interventions, with or without catheter directed thrombolysis.

Question 27

When is pulmonary thromboendarterectomy a suggested treatment option?

Answer 27

For patients with chronic thromboembolic pulmonary hypertension (CTEPH) and evaluated as candidates for this by an experienced thromboendarterectomy team

In selected patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are identified by an experienced thromboendarterectomy team, we suggest pulmonary thromboendarterectomy over no pulmonary thromboendarterectomy (Grade 2C). Remarks: Patients with CTEPH should be evaluated by a team with expertise in treatment of pulmonary hypertension. Pulmonary thromboendarterectomy is often lifesaving and life-transforming. Patients with CTEPH who are not candidates for pulmonary thromboendarterectomy may benefit from other mechanical and pharmacological interventions designed to lower pulmonary arterial pressure.

Question 28

Suggested treatment for acute upper extremity DVT of axillary or more proximal veins?

Answer 28

Anticoagulant therapy suggested over thrombolysis.

In patients with acute upper extremity DVT (UEDVT) that involves the axillary or more proximal veins, we suggest anticoagulant therapy alone over thrombolysis (Grade 2C). Remarks: Patients who (i) are most likely to benefit from thrombolysis (see text); (ii) have access to CDT; (iii) attach a high value to prevention of PTS; and (iv) attach a lower value to the initial complexity, cost, and risk of bleeding with thrombolytic therapy are likely to choose thrombolytic therapy over anticoagulation alone.

Question 29

After thrombolysis of AUEDVT, is the anticoagulant therapy the same as for those who don’t undergo thrombolysis?

Answer 29

Yes, use the same intensity and duration of anticoag therapy

In patients with UEDVT who undergo thrombolysis, we recommend the same intensity and duration of anticoagulant therapy as in patients with UEDVT who do not undergo thrombolysis (Grade 1B).

Question 30

What should you do with the anticoag therapy if a patient has a recurrent VTE while on therapeutic VKA or were compliant with a NOAC?

Answer 30

Suggest switching to LMWH temporarily (about 1 month) and consider the following:
If it was truly recurrent, or if it was a piece of the original VTE
If patient was truly compliant
Possibility of underlying malignancy

In patients who have recurrent VTE on VKA therapy (in the therapeutic range) or on dabigatran, rivaroxaban, apixaban, or edoxaban (and are believed to be compliant), we suggest switching to treatment with LMWH at least temporarily (Grade 2C). Remarks: Recurrent VTE while on therapeutic-dose anticoagulant therapy is unusual and should prompt the following assessments: (1) reevaluation of whether there truly was a recurrent VTE; (2) evaluation of compliance with anticoagulant therapy; and (3) consideration of an underlying malignancy. A temporary switch to LMWH will usually be for at least 1 month.

Question 31

What should you do if patient has a recurrent VTE while compliant on long-term LMWH?

Answer 31

Increase the dose of LMWH by 25-33%. Also reassess the following:
If VTE was truly recurrent,
If pt was truly compliant,
Possibility of underlying malignancy

In patients who have recurrent VTE on long-term LMWH (and are believed to be compliant), we suggest increasing the dose of LMWH by about one-quarter to one-third (Grade 2C). Remarks: Recurrent VTE while on therapeutic-dose anticoagulant therapy is unusual and should prompt the following assessments: (1) reevaluation of whether there truly was a recurrent VTE; (2) evaluation of compliance with anticoagulant therapy; and (3) consideration of an underlying malignancy.