American College of Chest Physicians Guideline on Antithrombotic Therapy for VTE Disease

SUMMARY:

The decision whether to prescribe anticoagulation (AC) for deep vein thrombosis (DVT) or pulmonary embolism (PE), and for what duration, is a highly individualized one that must take into account several clinical variables as well as patient preferences. Recommendations for AC are tailored based on a patient’s bleeding risk profile, characteristics of DVT (proximal vs. distal) and the clinical context in which VTE has occurred (provoked by a major transient risk factor present within 3 months of VTE, provoked by minor transient risk factor within 2 months of diagnosis, provoked by a persistent risk factor, or unprovoked). The American College of Chest Physicians offers a comprehensive evidence-based guideline on how and when to treat VTE with anticoagulation. The new guideline statement also provides guidance based on phase of management

Phase of Management

  • Initiation Phase (~5-21 days): Initial choice of anticoagulants
  • Treatment Phase (3 months): Treatment duration after the initiation phase
  • Extended Phase: (3 months – no planned stop date): Secondary prevention period without a planned stop date where anticoagulants are used at reduced or full doses

General Treatment Principles for VTE

  • Treatment phase should last 3 months
  • Patients with transient risk factors (both major and minor): Extended-phase anticoagulation is not recommended
  • Patients with unprovoked VTE or persistent risk factors
    • Offer extended-phase anticoagulation with Direct-Acting Oral Anticoagulants (DOACs)
    • DOACs (include apixaban, dabigatran, edoxaban, and rivaroxaban)
  • Offer vitamin K antagonists (VKAs), if cannot receive DOAC
  • Offer aspirin after completion of anti-coagulation therapy
    • Aspirin is not a reasonable alternative to therapy however is reasonable for prevention of recurrent VTE
  • Patients selected to receive extended phase therapy should be offered a reduced dose over full dose of apixaban or rivaroxaban | This is preferred over aspirin or no therapy
  • Compression stockings to prevent post-thrombotic syndrome (PTS) not recommended

Management of Pulmonary Embolism

Low-risk PE, Outpatient Treatment is Adequate for Initiation Phase Over Hospitalization

  • Must satisfy the following criteria
    • Clinically stable with cardiopulmonary reserve
    • No contra-indications, such as severe thrombocytopenia <50,000, severe renal or liver disease, and no recent bleeding
    • Patient can adhere to the proposed treatment regimen
    • Patient preference and comfort with initiation of therapy at home
  • First line treatment for VTE (either DVT of the leg or PE) first line includes apixaban, dabigatran, edoxaban, or rivaroxaban over VKAs
    • Apixaban 10mg oral twice daily for 7 days followed by 5mg twice daily
    • Rivaroxaban 15mg twice daily for 21 days followed by 20mg daily

Isolated subsegmental PE

  • Subsegmental PE without involvement of proximal pulmonary arteries without evidence of proximal DVT, can be managed with surveillance or anticoagulation based on risk for recurrence of VTE
    • Necessary to rule out DVT due to association of Isolated subsegmental PE with proximal DVTs (or another location if suspected)
    • Those at high risk for recurrent VTE should prompt management with anticoagulation over clinical surveillance

Asymptomatic Acute PE

  • Incidentally found asymptomatic pulmonary embolisms should be managed the same, both in the initiation phase and treatment phase as patients with symptomatic PEs
    • Similar outcomes as symptomatic PEs
    • For asymptomatic patients undergoing chest CTs, identified in 1% of outpatient and 4% of inpatient scans

Acute PE with symptoms

  • Acute PE with hypotension, defined as systolic BP <90mm Hg, thrombolytic therapy is recommended however due to lack of data between approaches, there is not one agent or dosing strategy recommended
  • Evaluate bleeding risk when considering thrombolytic therapy
  • Evidence of clinical deterioration after initiation of therapy, even without hypotension, should warrant thrombolytic therapy

Alternative Interventions in Acute PE

  • Catheter-assisted thrombus removal in patient with Acute PE
    • Systemic thrombolytic therapy is best administered via peripheral vein rather than catheter-directed thrombolysis
    • Consider catheter-assisted thrombus removal over no interventions if patients have an acute PE with hypotension and either (a) high bleeding risk (b) failed systemic thrombolysis or (c) shock with likely impending death before systemic thrombolysis can take affect
  • IVF Filter plus anticoagulation
    • Patients with acute DVT of the leg, routine placement of IVC filter is not recommended
    • Consider IVF filter if patients have a contra-indication to anticoagulation
    • Absolute contraindications include active major bleeding, severe thrombocytopenia, or CNS lesion with a high bleeding risk

Acute PE without symptoms

  • Acute PE without hypotension does not require thrombolytic therapy

Isolated Distal DVT – Updated Guidance

  • Acute isolated distal DVT of the leg should be managed based on symptoms and risk factors for extension
    • Those without severe symptoms or risk factors, serial imaging for two weeks can be chosen over anticoagulation
      • No anticoagulation if thrombus does not extend with serial imaging
      • If extends into proximal veins start anticoagulation
    • Severe symptoms or risk factors should be preferentially started with anticoagulation
    • Dosing for distal and proximal DVTs are the same for three months
    • Risk factors for extension include
      • Positive D-dimer | Extensive (>5 cm) thrombus | Thrombus close to proximal veins | No reversible provoking factor | Active cancer | Prior VTE | Inpatient status

Acute DVT

  • Acute DVT of the leg can be managed with anticoagulation therapy alone without additional interventions, such as thrombolytic, mechanical, or pharmaco-mechanical therapy
    • Severe, limb-threatening DVTs (phlegmasia or threatened venous gangrene) consider more rapid thrombus resolution
    • Treatment phase should last 3 months
    • Patients with transient risk factors (both major and minor), extended-phase anticoagulation is not recommended
    • Patients with unprovoked VTE or persistent risk factors should be offered extended-phase anticoagulation with DOAC | Offer VKA if cannot receive DOAC

Cancer-Associated Thrombosis

  • Patient with cancer-associated thrombosis (CAT)
    • Oral Xa inhibitors are recommended over low-molecular weight heparin for both initiation and treatment phase of therapy
  • Other organizations
    • 2016 AC Forum suggests LMWH for a minimum of six months
    • 2018 NCCN guidelines suggest LMWH preferred for the first six month
    • 2020 NICE guidelines suggest DOAC first line with transition to LMWH or warfarin in patients ineligible for DOAC

Note: In patients with CAT and luminal GI malignancy, there is a higher risk of major bleeding with edoxaban and rivaroxaban compared to LMWH and apixaban | Consider apixaban or LMWH for these patients!

Cerebral Vein Thrombosis (CVT)

  • Anticoagulation therapy recommended at minimum during the treatment phase
  • Applicable to both patients with and without intracranial hemorrhage as a complication of CVT

Special Considerations

Patients with acute VTE in the setting of Antiphospholipid Syndrome (APS)

  • Treatment phase recommendations include adjusted-dose VKA with a target INR of 2.5 over DOAC therapy
    • This is particularly important in patients positive for all three (lupus anti-coagulant, anti-cardiolipin, and anti-beta-2-glycoprotein antibodies) as well as those with arterial thrombosis
  • Initiation phase should include an overlapping period of parenteral anticoagulation prior to initiating VKA therapy

Superficial vein thrombosis

  • Some cases of superficial venous thrombosis (SVT) are at increased risk of clot progression to DVT or PE and warrant use of anti-coagulation for 45 days over no therapy
  • Risk factors include
    • Extensive SVT
    • Involvement above the knee or close to the saphenofemoral junction
    • Severe symptoms
    • Involvement of the greater saphenous vein
    • History of VTE or SVT
    • Active cancer
    • Recent surgery

KEY POINTS:

  • Treatment phase for acute VTE should last 3 months
  • Extended-phase anticoagulation treatment is not needed if risk factors are transient
  • Aspirin is not a reasonable alternative to therapy however is reasonable for prevention of recurrent VTE after completion of therapy
  • Patients selected to receive extended phase therapy should be offered a reduced dose over full dose of apixaban or rivaroxaban over aspirin or no therapy
  • Consider thrombolytic therapy in patients with a PE that are hemodynamically unstable
  • Previous scenarios where anticoagulation was not recommended, such as superficial DVTs, may warrant a shorter duration of anticoagulation therapy for 45 days based on risk factors for progression of thrombus

Learn More – Primary Sources

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report – Executive Summary – CHEST (chestnet.org)