The grades of recommendation (1A, 1B, 1C, 2A, 2B, 2C) are defined at the end of the "Major Recommendations" field.
Initial Anticoagulation of Acute Deep Vein Thrombosis (DVT) of the Leg
- For patients with objectively confirmed DVT, the guideline developers recommend short-term treatment with subcutaneous (SC) low-molecular-weight heparin (LMWH) (Grade 1A), intravenous (IV) unfractionated heparin (UFH) (Grade 1A), monitored SC UFH (Grade 1A), fixed-dose SC UFH (Grade 1A), or SC fondaparinux (Grade 1A) rather than no such short-term treatment.
- For patients with a high clinical suspicion of DVT, the guideline developers recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C).
- In patients with acute DVT, the guideline developers recommend initial treatment with LMWH, UFH, or fondaparinux for at least 5 days and until the international normalized ration (INR) is > 2.0 for 24 hours (Grade 1C).
- In patients with acute DVT, the guideline developers recommend initiation of vitamin K antagonists (VKA) together with LMWH, UFH, or fondaparinux on the first treatment day rather than delayed initiation of VKA (Grade 1A).
IV UFH for the Initial Treatment of DVT
In patients with acute DVT, if IV UFH is chosen, the guideline developers recommend that, after an initial IV bolus (80 U/kg or 5,000 U) it be administered by continuous infusion (initially at a dose of 18 U/kg/h or 1,300 U/h) with dose adjustment to achieve and maintain an activated partial thromboplastin time (APTT) prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity by the amidolytic assay rather than administration as IV boluses throughout treatment, or administration without coagulation monitoring (Grade 1C).
SC UFH Compared with IV Heparin for the Initial Treatment of DVT
- In patients with acute DVT, if monitored SC UFH is chosen, the guideline developers recommend an initial dose of 17,500 U, or a weight-adjusted dose of about 250 U/kg, twice a day (bid), with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity when measured 6 hours after injection rather than starting with a smaller initial dose (Grade 1C) (See also Section 1.5 in the original guideline document).
- In patients with acute DVT, if fixed-dose, unmonitored SC UFH is chosen, the guideline developers recommend an initial dose of 333 U/kg followed by 250 U/kg bid rather than non-weight-based dosing (Grade 1C) (See also Section 1.5 in the original guideline document).
LMWH for the Initial Treatment of DVT
- In patients with acute DVT, the guideline developers recommend initial treatment with LMWH SC once or twice daily, as an outpatient if possible (Grade 1C) or as an inpatient if necessary (Grade1A), rather than treatment with IV UFH.
- In patients with acute DVT treated with LMWH, the guideline developers recommend against routine monitoring with anti-factor Xa level measurements (Grade 1A).
- In patients with acute DVT and severe renal failure, the guideline developers suggest UFH over LMWH (Grade 2C).
Catheter-Directed Thrombolysis for Acute DVT
- In selected patients with extensive acute proximal DVT (e.g., iliofemoral DVT, symptoms for < 14 days, good functional status, life expectancy of >1 year) who have a low risk of bleeding, the guideline developers suggest that catheter-directed thrombolysis (CDT) may be used to reduce acute symptoms and post-thrombotic morbidity if appropriate expertise and resources are available (Grade 2B).
- After successful CDT in patients with acute DVT, the guideline developers suggest correction of underlying venous lesions using balloon angioplasty and stents (Grade 2C).
- The guideline developers suggest pharmacomechanical thrombolysis (e.g., with inclusion of thrombus fragmentation and/or aspiration) in preference to CDT alone to shorten treatment time if appropriate expertise and resources are available (Grade 2C).
- After successful CDT in patients with acute DVT, the guideline developers recommend the same intensity and duration of anticoagulant therapy as for comparable patients who do not undergo CDT (Grade 1C).
Systemic Thrombolytic Therapy for Acute DVT
In selected patients with extensive proximal DVT (e.g., symptoms for < 14 days, good functional status, life expectancy of >1 year) who have a low risk of bleeding, the guideline developers suggest that systemic thrombolytic therapy may be used to reduce acute symptoms and postthrombotic morbidity if CDT is not available (Grade 2C).
Percutaneous Venous Thrombectomy
In patients with acute DVT, the guideline developers suggest that they should not be treated with percutaneous mechanical thrombectomy alone (Grade 2C).
Operative Venous Thrombectomy for Acute DVT
- In selected patients with acute iliofemoral DVT (e.g., symptoms for < 7 days, good functional status, and life expectancy of >1 year), the guideline developers suggest that operative venous thrombectomy may
be used to reduce acute symptoms and postthrombotic morbidity if appropriate expertise and resources are available (Grade 2B). If such patients do not have a high risk of bleeding, the guideline developers suggest that catheter-directed thrombolysis is usually preferable to operative venous thrombectomy (Grade 2C).
- In patients who undergo operative venous thrombectomy, the guideline developers recommend the same intensity and duration of anticoagulant therapy afterwards as for comparable patients who do not undergo venous thrombectomy (Grade 1C).
Vena Caval Filters for the Initial Treatment of DVT
- For patients with DVT, the guideline developers recommend against the routine use of a vena cava filter in addition to anticoagulants (Grade 1A).
- For patients with acute proximal DVT, if anticoagulant therapy is not possible because of the risk of bleeding, the guideline developers recommend placement of an inferior vena cava filter (Grade 1C).
- For patients with acute DVT who have an inferior vena cava (IVC) filter inserted as an alternative to anticoagulation, the guideline developers recommend that they should subsequently receive a conventional course of anticoagulant therapy if their risk of bleeding resolves (Grade 1C).
Immobilization for the Treatment of Acute DVT
In patients with acute DVT, the guideline developers recommend early ambulation in preference to initial bed rest when this is feasible (Grade 1A).
Duration of Anticoagulant Therapy
- For patients with DVT secondary to a transient (reversible) risk factor, the guideline developer recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A).
- For patients with unprovoked DVT, the guideline developers recommend treatment with a VKA for at least 3 months (Grade 1A). They recommend that after 3 months of anticoagulant therapy, all patients with unprovoked DVT should be evaluated for the risk-benefit ratio of long-term therapy (Grade 1C). For patients with a first unprovoked VTE that is a proximal DVT, and in whom risk factors for bleeding are absent and for whom good anticoagulant monitoring is achievable, the guideline developers recommend long-term treatment (Grade 1A).
Underlying values and preferences: This recommendation attaches a relatively high value to prevention of recurrent VTE and a lower value to the burden of long-term anticoagulant therapy.
For patients with a second episode of unprovoked VTE, the guideline developers recommend long-term treatment (Grade 1A). For patients with a first isolated distal DVT that is unprovoked, the guideline developers suggest that 3 months of anticoagulant therapy is sufficient rather than indefinite therapy (Grade 2B).
- For patients with DVT and cancer, the guideline developers recommend LMWH for the first 3 to 6 months of long-term anticoagulant therapy (Grade 1A). For these patients, the guideline developers recommend subsequent anticoagulant therapy with VKA or LMWH indefinitely or until the cancer is resolved (See Section 2.4 in the original guideline document). (Grade 1C).
- In patients who receive long-term anticoagulant treatment, the risk-benefit ratio of continuing such treatment should be reassessed in the individual patient at periodic intervals (Grade 1C).
Intensity of Anticoagulant Effect
- In patients with DVT, the guideline developers recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (range, 2.0 to 3.0) for all treatment durations (Grade 1A). For patients with unprovoked DVT who have a strong preference for less frequent INR testing to monitor their therapy, after the first 3 months of conventional-intensity anticoagulation (INR range, 2.0 to 3.0), the guideline developers recommend low-intensity therapy (range, 1.5 to 1.9) with less frequent INR monitoring over stopping treatment (Grade 1A). The guideline developers recommend against high-intensity VKA therapy (INR range, 3.1 to 4.0) compared to an INR range of 2.0 to 3.0 (Grade 1A).
Treatment of Asymptomatic DVT of the Leg
- In patients who are unexpectedly found to have asymptomatic DVT, the guideline developers recommend the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT (Grade 1C).
Elastic Stockings and Compression Bandages To Prevent Postthrombotic Syndrome (PTS)
For a patient who has had a symptomatic proximal DVT, the guideline developers recommend the use of an elastic compression stocking with an ankle pressure gradient of 30 to 40 mm Hg if feasible (Grade 1A). Compression therapy, which may include use of bandages acutely, should be started as soon as feasible after starting anticoagulant therapy and should be continued for a minimum of 2 years, and longer if patients have symptoms of the postthrombotic syndrome (PTS). (Note: feasibility, both short and long term, refers to ability of patients and their caregivers to apply and remove stockings.)
Underlying values and preferences: This recommendation attaches a relatively high value to long-term prevention of the postthrombotic syndrome (PTS) and a low value to the burden (e.g., inconvenience or discomfort) associated with wearing stockings.
Physical Treatment of PTS without Venous Leg Ulcers
- For patients with severe edema of the leg due to PTS, the guideline developers suggest a course of intermittent pneumatic compression (IPC) (Grade 2B).
- For patients with mild edema of the leg due to PTS, the guideline developers suggest the use of elastic compression stockings (Grade 2C).
Physical Treatment of Venous Leg Ulcers
In patients with venous ulcers resistant to healing with wound care and compression, the guideline developers suggest the addition of intermittent pneumatic compression (IPC) (Grade 2B).
Hyperbaric Oxygen and the Management of Patients with Venous Ulcers
For patients with venous ulcers, the guideline developers suggest that hyperbaric oxygen not be used (Grade
2B).
Pentoxifylline
In patients with venous leg ulcers, the guideline developers suggest pentoxifylline, 400 mg orally three times a day, in addition to local care and compression and/or IPC (Grade 2B).
Micronized Purified Flavonoid Fraction or Sulodexide for the Treatment of Venous Leg Ulcers
In patients with persistent venous ulcers, the guideline developers suggest that rutosides, in the form of micronized purified flavonoid fraction administered orally, or sulodexide administered intramuscularly and then orally, be added to local care and compression (Grade 2B).
IV or SC UFH, SC LMWH, SC Fondaparinux, and VKA for the Initial Treatment of Pulmonary Embolism (PE)
- For patients with objectively confirmed pulmonary embolism (PE), the guideline developers recommend short-term treatment with SC LMWH (Grade 1A), IV UFH (Grade 1A), monitored SC UFH (Grade 1A), fixed-dose SC UFH (Grade 1A), or SC fondaparinux (Grade
1A) rather than no such acute treatment. Patients with acute PE should also be routinely assessed for treatment with thrombolytic therapy (see the "Systemically and Locally Administered Thrombolytic Therapy for PE" section below for related discussion and recommendations).
- For patients in whom there is a high clinical suspicion of PE, the guideline developers recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C).
- In patients with acute PE, the guideline developers recommend initial treatment with LMWH, UFH, or fondaparinux for at least 5 days and until the INR is >2.0 for at least 24 hours (Grade 1C).
- In patients with acute PE, the guideline developers recommend initiation of VKA together with LMWH, UFH, or fondaparinux on the first treatment day rather than delayed initiation of VKA (Grade 1A).
- In patients with acute PE, if IV UFH is chosen, the guideline developers recommend that after an initial IV bolus (80 U/kg or 5,000 U), it is administered by continuous infusion (initially at dose of 18 U/kg/h or 1,300 U/h) with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity by the amidolytic assay rather than administration as IV boluses throughout treatment, or administration without coagulation monitoring (Grade 1C).
- In patients with acute PE, if monitored SC UFH is chosen, the guideline developers recommend an initial dose of 17,500 U, or a weight-adjusted dose of about 250 U/kg, bid, with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity when measured 6 hours after injection rather than starting with a smaller initial dose (Grade 1C).
- In patients with acute PE, if fixed-dose, unmonitored SC UFH is chosen, the guideline developers recommend an initial dose of 333 U/Kg followed by a twice-daily dose of 250 U/kg rather than non–weight-based dosing (Grade 1C).
- In patients with acute nonmassive PE, the guideline developers recommend initial treatment with LMWH over IV UFH (Grade 1A). In patients with massive PE, in other situations where there is concern about SC absorption, or in patients for whom thrombolytic therapy is being considered or planned, the guideline developers suggest IV UFH over SC LMWH, SC fondaparinux, or SC UFH (Grade 2C).
- In patients with acute PE treated with LMWH, the guideline developers recommend against routine monitoring with anti-factor Xa level measurements (Grade 1A).
- In patients with acute PE and severe renal failure, the guideline developers suggest UFH over LMWH (Grade
2C).
Systemically and Locally Administered Thrombolytic Therapy for PE
- All PE patients should undergo rapid risk stratification (Grade 1C). For patients with evidence of hemodynamic compromise, the guideline developers recommend use of thrombolytic therapy unless there are major contraindications owing to bleeding risk (Grade 1B). Thrombolysis in these patients should not be delayed, because irreversible cardiogenic shock may ensue. In selected high-risk patients without hypotension who are judged to have a low risk of bleeding, the guideline developers suggest administration of thrombolytic therapy (Grade 2B). The decision to use thrombolytic therapy depends on the clinician's assessment of PE severity, prognosis, and risk of bleeding. For the majority of patients with PE, the guideline developers recommend against using thrombolytic therapy (Grade 1B).
- In patients with acute PE, when a thrombolytic agent is used, the guideline developers recommend that treatment be administered via a peripheral vein rather than placing a pulmonary artery catheter to administer treatment (Grade 1B).
- In patients with acute PE, with administration of thrombolytic therapy, the guideline developers recommend use of regimens with short infusion times (e.g., a 2-hour infusion) over those with prolonged infusion times (e.g., a 24-hour infusion) (Grade 1B).
Catheter Extraction or Fragmentation for the Initial Treatment of PE
For most patients with PE, the guideline developers recommend against use of interventional catheterization techniques (Grade 1C). In selected highly compromised patients who are unable to receive thrombolytic therapy because of bleeding risk, or whose critical status does not allow sufficient time for systemic thrombolytic therapy to be effective, the guideline developers suggest use of interventional catheterization techniques if appropriate expertise is available (Grade 2C).
Pulmonary Embolectomy for the Initial Treatment of PE
In selected highly compromised patients who are unable to receive thrombolytic therapy because of bleeding risk, or whose critical status does not allow sufficient time for systemic thrombolytic therapy to be effective, the guideline developers suggest that pulmonary embolectomy may be used if appropriate expertise is available (Grade 2C).
Vena Caval Filters for the Initial Treatment of PE
- For most patients with PE, the guideline developers recommend against the routine use of a vena caval filter in addition to anticoagulants (Grade 1A).
- In patients with acute PE, if anticoagulant therapy is not possible because of risk of bleeding, the guideline developers recommend placement of an IVC filter (Grade 1C).
- For patients with acute PE who have an IVC filter inserted as an alternative to anticoagulation, the guideline developers recommend that they should subsequently receive a conventional course of anticoagulant therapy if their risk of bleeding resolves (Grade 1C).
Long-term Treatment of Acute PE
- For patients with PE secondary to a transient (reversible) risk factor, the guideline developers recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A).
- For patients with unprovoked PE, the guideline developers recommend treatment with a VKA for at least 3 months (Grade 1A). The guideline developers recommend that after 3 months of anticoagulant therapy, all patients with unprovoked PE should be evaluated for the risk-benefit ratio of long-term therapy (Grade 1C). For patients with a first unprovoked episode of VTE that is a PE, and in whom risk factors for bleeding are absent and for whom good anticoagulant monitoring is achievable, the guideline developers recommend long-term treatment (Grade 1A).
Underlying values and preferences: This recommendation attaches a relatively high value to prevention of recurrent VTE and a lower value to the burden of long-term anticoagulant therapy.
For patients with a second episode of unprovoked VTE, the guideline developers recommend long-term treatment (Grade 1A).
- For patients with PE and cancer, the guideline developers recommend LMWH for the first 3 to 6 months of long-term anticoagulant therapy (Grade 1A). For these patients, the guideline developers recommend subsequent anticoagulant therapy with VKA or LMWH indefinitely or until the cancer is resolved (Grade 1C).
- In patients who receive long-term anticoagulant treatment, the risk-benefit ratio of continuing such treatment should be reassessed in the individual patient at periodic intervals (Grade 1C).
- In patients with PE, the guideline developers recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). For patients with unprovoked PE who have a strong preference for less frequent INR testing to monitor their therapy, after the first 3 months of conventional-intensity anticoagulation (INR range, 2.0 to 3.0), the guideline developers recommend low-intensity therapy (INR range, 1.5 to 1.9) with less frequent INR monitoring over stopping treatment (Grade
1A). The guideline developers recommend against high-intensity VKA therapy (INR range, 3.1 to 4.0) compared with an INR range of 2.0 to 3.0 (Grade 1A).
- In patients who are unexpectedly found to have asymptomatic PE, the guideline developers recommend the same initial and long-term anticoagulation as for comparable patients with symptomatic PE (Grade 1C).
Pulmonary Thromboendarterectomy, VKA, and Vena Caval Filter for the Treatment of Chronic Thromboembolic Pulmonary Hypertension (CTPH)
- In selected patients with chronic CTPH, such as those with central disease under the care of an experienced surgical/medical team, the guideline developers recommend pulmonary thromboendarterectomy (Grade 1C).
- For all patients with CTPH, the guideline developers recommend life-long treatment with a VKA targeted to an INR of 2.0 to 3.0 (Grade 1C).
- For patients with CTPH undergoing pulmonary thromboendarterectomy, the guideline developers suggest the placement of a permanent vena caval filter before or at the time of the procedure (Grade 2C).
- For patients with inoperable CTPH, the guideline developers suggest referral to a center with expertise in pulmonary hypertension so that patients can be evaluated for alternative treatments, such as vasodilator therapy or balloon pulmonary angioplasty (Grade 2C).
Treatment of Infusion Thrombophlebitis
For patients with symptomatic infusion thrombophlebitis as a complication of IV infusion, the guideline developers suggest oral diclofenac or another nonsteroidal anti-inflammatory drug (Grade 2B), topical diclofenac gel (Grade 2B), or heparin gel (Grade 2B) until resolution of symptoms or for up to 2 weeks. The guideline developers recommend against the use of systemic anticoagulation (Grade 1C).
Treatment of Superficial Vein Thrombosis (SVT)
For patients with spontaneous superficial vein thrombosis, the guideline developers suggest prophylactic or intermediate doses of LMWH (Grade 2B) or intermediate doses of UFH (Grade 2B) for at least 4 weeks. The guideline developers suggest that as an alternative to 4 weeks of LMWH or UFH, VKA (target INR, 2.5; range, 2.0 to 3.0) can be overlapped with 5 days of UFH and LMWH and continued for 4 weeks (Grade
2C). The guideline developers suggest that oral nonsteroidal anti-inflammatory drugs should not be used in addition to anticoagulation (Grade 2B). The guideline developers recommend medical treatment with anticoagulants over surgical treatment (Grade 1B).
Remark: It is likely that less extensive superficial vein thrombosis (i.e., where the affected venous segment is short in length or further from the saphenofemoral junction) does not require treatment with anticoagulants. It is reasonable to use oral or topical nonsteroidal anti-inflammatory drugs for symptom control in such cases.
IV UFH or LMWH for the Initial Treatment of Upper-Extremity DVT
For patients with acute upper-extremity DVT (UEDVT), the guideline developers recommend initial treatment with therapeutic doses of LMWH, UFH, or fondaparinux as described for leg DVT (see the "Initial Anticoagulation of Acute DVT of the Leg" section above) (Grade 1C).
Thrombolytic Therapy for the Initial Treatment of UEDVT
- For most patients with acute UEDVT, the guideline developers recommend against the routine use of systemic or catheter-directed thrombolytic therapy (Grade 1C).
- In selected patients with acute UEDVT (e.g., in those with a low risk of bleeding and severe symptoms of recent onset) the guideline developers suggest that catheter-directed thrombolysis (CDT) may be used for initial treatment if appropriate expertise and resources are available (Grade 2C).
Catheter Extraction, Surgical Thrombectomy, Transluminal Angioplasty, Stent Placement, Staged Approach of Lysis Followed by Interventional or Surgical Procedure, and Superior Vena Cava Filter Insertion, for the Initial Treatment of UEDVT
- For most patients with acute UEDVT, the guideline developers recommend against the routine use of catheter extraction, surgical thrombectomy, transluminal angioplasty, stent placement, staged approach of lysis followed by interventional or surgical procedure, or superior vena cava filter placement (Grade 1C).
- In selected patients with acute UEDVT (e.g., those with primary UEDVT and failure of anticoagulant or thrombolytic treatment who have severe persistent symptoms), the guideline developers suggest that catheter extraction, surgical thrombectomy, transluminal angioplasty, or a staged approach of lysis followed by a vascular interventional or surgical procedure may be used, if appropriate expertise and resources are available (all Grade 2C).
- In selected patients with acute UEDVT (e.g., those in whom anticoagulant treatment is contraindicated and there is clear evidence of DVT progression or clinically significant PE), the guideline developers suggest placement of a superior vena cava (SVC) filter (Grade 2C).
Anticoagulants for the Long-term Treatment of UEDVT
- For patients with acute UEDVT, the guideline developers recommend treatment with a VKA for >3 months (Grade 1C).
Remark: A similar process as for lower-extremity DVT (see the "Duration of Anticoagulant Therapy" section above) should be used to determine the optimal duration of anticoagulation.
- For most patients with UEDVT in association with an indwelling central venous catheter, the guideline developers suggest that the catheter not be removed if it is functional and there is an ongoing need for the catheter (Grade 2C).
- For patients who have UEDVT in association with an indwelling central venous catheter that is removed, the guideline developers do not recommend that the duration of long-term anticoagulant treatment be shortened to < 3 months (Grade 2C).
Prevention of Post-thrombotic Syndrome (PTS) of the Arm
For patients at risk for PTS after UEDVT, the guideline developers do not suggest routine use of elastic compression or venoactive medications (Grade 2C).
Treatment of PTS of the Arm
In patients with UEDVT who have persistent edema and pain, the guideline developers suggest elastic bandages or elastic compression sleeves to reduce symptoms of PTS of the upper extremity (Grade 2C).
Definitions:
| Grading Recommendation |
| Grade of Recommendation* |
Benefit vs. Risk and Burdens |
Methodologic Quality of Supporting Evidence |
Implications |
| Strong recommendation, high-quality evidence, Grade 1A |
Desirable effects clearly outweigh undesirable effects, or vice versa |
Consistent evidence from RCTs without important limitations or exceptionally strong evidence from observational studies |
Recommendation can apply to most patients in most circumstances; further research is very unlikely to change our confidence in the estimate of effect |
| Strong recommendation, moderate-quality evidence, Grade 1B |
Desirable effects clearly outweigh undesirable effects, or vice versa |
Evidence from RCTs with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence from observational studies |
Recommendation can apply to most patients in most circumstances; higher quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate |
| Strong recommendation, low or very low-quality evidence, Grade 1C |
Desirable effects clearly outweigh undesirable effects, or vice versa |
Evidence for at least one critical outcome from observational studies, case series, or from RCTs with serious flaws or indirect evidence |
Recommendation can apply to most patients in many circumstances; higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate |
| Weak recommendation, high-quality evidence, Grade 2A |
Desirable effects closely balanced with undesirable effects |
Consistent evidence from RCTs without important limitations or exceptionally strong evidence from observational studies |
The best action may differ depending on circumstances or patient or society values; further research is very unlikely to change our confidence in the estimate of effect |
| Weak recommendation, moderate-quality evidence, Grade 2B |
Desirable effects closely balanced with undesirable effects |
Evidence from RCTs with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence from observational studies |
Best action may differ depending on circumstances or patient or society values; higher-quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate |
| Weak recommendation, low or very low-quality evidence, Grade 2C |
Desirable effects closely balanced with undesirable effects |
Evidence for at least one critical outcome from observational studies, case series, or from RCTs with serious flaws or indirect evidence |
Other alternatives may be equally reasonable; higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate |
*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.
