2012 CHEST Guideline Update
VTE prophylaxis, DVT treatment, and Atrial Fibrillation
LT Tabatha Welker, PharmD
Pharmacy Resident, PHS Claremore Indian Hospital
Objectives
• Explain how to treat a patient with diagnosed
DVT of the leg
• Apply knowledge of VTE prophylaxis to a
patient case
• State the recommended anticoagulation
management for patients with Atrial
Fibrillation (AF)
2
Overview
• CHEST Grades of Recommendations
• VTE Prophylaxis
– Nonsurgical Patients
– Nonorthopedic Surgical Patients
• DVT Treatment (of the leg)
• Atrial Fibrillation Management
3
INTERPRETATION OF RECOMMENDATIONS
Grade
Recommendation
Methodological
Quality
Evidence
Benefit vs.
Burdens
Implication
1A
Strong
Consistent evidence
from RCTs without
limitations or very
strong evidence from
observational studies
High
Quality
“clearly
outweighs”
Can apply to most patients
in most circumstances;
further research unlikely
to change confidence
1B
Strong
Evidence from RCT’s
with important
limitations or very
strong evidence from
observation studies
Moderate
Quality
“clearly
outweighs”
Can apply to most patients
in most circumstances;
higher quality research
may well have important
impact on confidence in
estimate of effect
1C
Strong
Evidence for at least 1
critical outcome from
observational studies,
case series or from RCT‘s
with serious flaws or
indirect evidence
Low or very
low Quality
“clearly
outweighs”
Can apply to most patients
in many circumstances;
higher quality research is
likely to have an important
impact on confidence and
may well change estimate
4
INTERPRETATION OF RECOMMENDATIONS
Grade
Recommendation
Methodological
Quality
Evidence
Benefit vs.
Burdens
Implication
2A
Weak
Consistent evidence
from RCTs without
limitations or very
strong evidence from
observational studies
High
Quality
“closely
balanced”
The best action may differ
depending on circumstances
or patient/society values;
further research is unlikely to
change confidence in estimate
of effect
2B
Weak
Evidence from RCT’s
with important
limitations or very
strong evidence from
observation studies
Moderate
Quality
“closely
balanced”
The best action may differ
depending on circumstances
or patient/society values;
higher quality research may
have an important impact on
confidence and may change
estimate
2C
Weak
Evidence for at least 1
critical outcome from
observational studies,
case series or from
RCT’s with serious flaws
or indirect evidence
Low or
very low
Quality
“closely
balanced”
Other alternatives may be
equally reasonable; higher
quality research is likely to
have an important impact on
confidence of effect and may
well change estimate
5
VTE PROPHYLAXIS
PREVENTION OF VTE
IN NONSURGICAL PATIENTS
7
Hospitalized Acutely Ill
Medical Patients
• Increased risk of thrombosis, recommend anticoagulant
thromboprophylaxis with low molecular-weight heparin
(LMWH), low-dose unfractionated heparin (LDUH) bid,
LDUH tid, or fondaparinux (Grade 1B)
• Low risk of thrombosis, we recommend against the use of
pharmacologic prophylaxis or mechanical prophylaxis
(Grade 1B)
• Patients who are bleeding or at high risk of bleeding, we
recommend against anticoagulant thromboprophylaxis
(Grade 1B)
8
Hospitalized Acutely Ill
Medical Patients
• Patients at increased risk of thrombosis who are
bleeding or at high risk for major bleeding
– Optimal use of mechanical thromboprophylaxis with
graduated compression stockings (GCS) (Grade 2C)
– intermittent pneumatic compressions (IPC) (grade 2C)
• When bleeding risk decreases, and if VTE risk
persists
– pharmacologic thromboprophylaxis be substituted for
mechanical thromboprophylaxis (Grade 2B)
9
Hospitalized Acutely Ill
Medical Patients
• In acutely ill hospitalized medical patients who
receive an initial course of
thromboprophylaxis, we suggest against
extending duration of thromboprophylaxis
beyond the period of patient immobilization
or acute hospital stay (Grade 2B)
10
Critically Ill Patients
• Suggest against routine ultrasound screening for DVT
(2C)
• Suggest using LMWH or LDUH thromboprophylaxis
over no prophylaxis (2C)
• Bleeding or high risk for major bleeding, suggest
mechanical thromboprophylaxis with GCS (Grade 2C)
or IPC (Grade 2C) until the bleeding risk decreases
• When bleeding risk decreases, suggest that
pharmacologic thromboprophylaxis be substituted
for mechanical thromboprophylaxis (Grade 2C)
11
Cancer in the Outpatient Setting
• No additional risk factors for VTE, we suggest against
routine prophylaxis with LMWH or LDUH (grade 2B) and
recommend against the prophylactic use of VKAs (1B)
• In outpatients with solid tumors who have additional risk
factors for VTE and who are at low risk of bleeding, we
suggest prophylactic-dose LMWH or LDUH over no
prophylaxis (2B)
• In outpatient with cancer and indwelling central venous
catheters, we suggest against routine prophylaxis with
LMWH or LDUH (2B) and suggest against the prophylactic
use of VKAs (2C)
12
Chronically Immobilized Patients
• In chronically immobilized persons residing at
home or at a nursing home, we suggest
against the routine use of thromboprophylaxis
(2C)
13
Persons Traveling Long-Distance
• For long-distance travelers at increased risk of VTE
(including previous VTE, recent surgery or trauma, active
malignancy, pregnancy, estrogen use, advanced age, limited
mobility, severe obesity, or known thrombophilic disorder)
– frequent ambulation, calf muscle exercise, or sitting in an aisle
seat if feasible (2C)
– Suggest the use of properly fitted, below-knee GCS providing 15
to 30 mm Hg of pressure at the ankle during travel (2C).
• For all other long-distance travelers, we suggest against the
use of GCS (2C)
• For long-distance travelers, we suggest against the use of
aspirin or anticoagulants to prevent VTE (2C)
14
PREVENTION OF VTE IN
NONORTHOPEDIC SURGICAL PATIENTS
Patient undergoing General, GI, Urological, Gynecologic,
Bariatric, Vascular, Plastic, or Reconstructive Surgery
15
General and Abdominal-Pelvic Surgery
• Very low risk of VTE (<0.5%; Rogers score, <7; Caprini score, 0)
– No specific pharmacologic (Grade 1B) or mechanical (Grade 2C)
prophylaxis be used other than early ambulation
• Low risk for VTE (~1.5%, Rogers score, 7-10; Caprini score, 1-2)
– Mechanical prophylaxis, preferably with intermittent pneumatic
compression (IPC), over no prophylaxis (Grade 2C)
• Moderate risk for VTE (~3.0%; Rogers score, >10; Caprini score
3-4) who are not at high risk for major bleeding complications
– LMWH (Grade 2B), LDUH (Grade 2B), or mechanical prophylaxis,
preferably with IPC (Grade 2C), over no prophylaxis
16
General and Abdominal-Pelvic Surgery
• Moderate risk for VTE (3.0%; Rogers score, > 10; Caprini score,
3-4) who are at high risk for major bleeding complications or
those in whom the consequences of bleeding are thought to
be particularly severe
– mechanical prophylaxis, preferably with IPC, over no
prophylaxis (Grade 2C)
• High risk for VTE (~6.0%; Caprini score, ≥ 5) who are not at
high risk for major bleeding complications
– pharmacologic prophylaxis with LMWH (Grade 1B) or
LDUH (Grade 1B) over no prophylaxis
– Mechanical prophylaxis with elastic stockings or IPC should
be added to pharmacologic prophylaxis (Grade 2C)
17
General and Abdominal-Pelvic Surgery
• High-VTE-risk patients undergoing abdominal or pelvic
surgery for cancer who are not otherwise at high risk for
major bleeding complication, we recommend extendedduration pharmacologic prophylaxis (4 weeks) with LMWH
over limited-duration prophylaxis (Grade 1B)
• High-VTE-risk patients who are at high risk for major bleeding
complications or those in whom the consequences or those in
whom the consequences of bleeding are thought to be
particularly severe, we suggest use of mechanical prophylaxis,
preferably with IPC, over no prophylaxis until the risk of
bleeding diminishes and pharmacologic prophylaxis may be
initiated (Grade 2C).
18
General and Abdominal-Pelvic Surgery
• High risk for VTE (6%; Caprini score, ≥ 5) in whom both
LMWH and unfractionated heparin are contraindicated or
unavailable and who are not at high risk for major bleeding
complications
– low-dose aspirin (Grade 2C), fondaparinux (grade 2C), or
mechanical prophylaxis, preferably with IPC (Grade 2C), over no
prophylaxis.
• Inferior vena cava (IVC) filter should not be used for
primary VTE prevention (Grade 2C)
• Periodic surveillance with venous compression ultrasound
should not be performed (Grade 2C)
19
VTE TREATMENT
Deep Vein Thrombosis
• DVT of the leg
• Acute DVT
– Isolated distal
– Isolated proximal
– Provoked
– Non-provoked
• Recurrent DVT
21
Acute Isolated Distal DVT
• Without severe symptoms or risk factors for
extension, suggest serial imaging of the deep
veins for 2 weeks over initial anticoagulation (2C)
• With severe symptoms or risk factors for
extension, suggest initial anticoagulation over
serial imaging of the deep veins (2C)
• Patients that are managed with anticoagulation
should be managed the same as for patients with
acute proximal DVT (1B)
22
Acute Isolated Distal DVT
• Patients managed with serial imaging
– No anticoagulation if the thrombus does not
extend (1B)
– Anticoagulation if the thrombus extends but
remains confined to the distal veins (2C)
– Anticoagulation if the thrombus extends into the
proximal veins (1B)
23
Deep Vein Thrombosis
• In patients with acute DVT of the leg treated with
vitamin K antagonist (VKA), suggest initial treatment
with parental anticoagulation (1B)
• Intermediate to high clinical suspicion of acute VTE,
treat with parental anticoagulants if the results of
diagnostic test are expected to be delayed for more
than 4 hours (2C)
• Low clinical suspicion of an acute VTE, do not treat
with parental anticoagulants while awaiting results,
provided tests results are expected within 24 hours
(2C)
24
Parental Anticoagulation
• In patients with acute DVT of the leg, suggest
LMWH or fondaparinux over IV UFH (2C) and
over SC UFH (2B for LMWH; 2C for fondaparinux)
• In patients with acute DVT of the leg treated with
LMWH, suggest once- over twice-daily
administration (2C)
– Only when the approved once daily regimen uses the
same daily dose as the twice-daily regimen (i.e.
contains double the dose of the twice-daily injection)
25
When to initiate VKA?
• Same day as parental therapy
• Continue parental anticoagulation for a
minimum of 5 days AND until the INR is 2.0 or
greater for at least 24 hours (1B)
26
INR Range
• DVT of the leg treated with VKA, therapeutic
INR range of 2.0 to 3.0 (1B) is recommended
for all treatment durations
27
Phases of anticoagulation
Initial
Long-term
Extended
(0 to ~7 days)
(~7 days to ~3 months)
(~3 months to indefinite)
Parenteral*
Vitamin K antagonist or other agent
(LMWH, dabigatran, rivaroxaban)
*heparin, LMWH, fondaparinux
28
DURATION OF THERAPY
29
Proximal DVT of the leg
• Provoked by surgery = 3 months (1B)
• Provoked by nonsurgical transient factor = 3
months (1B)
• First unprovoked
– Low to moderate bleeding risk = extended therapy
over 3 months (2B)
– High bleeding risk = 3 months (1B)
30
Isolated Distal DVT of the leg
• Provoked by surgery = 3 months
• Provoked by nonsurgical transient risk factor =
3 months
• First unprovoked = 3 months regardless of
bleeding risk (2B low or moderate, 1B high)
31
Second Unprovoked DVT
• Low bleeding risk = Extended anticoagulation
therapy over 3 months (1B)
• Moderate bleeding risk = Extended
anticoagulation therapy over 3 months (2B)
• High bleeding risk = 3 months (2B)
32
Active Cancer
• DVT of the leg and active cancer
– Extended anticoagulation therapy over 3 months
(1B,2B)
• First line: LMWH (2B)
• Second line: VKA therapy (2B)
33
Inpatient or Outpatient?
• In patients with acute DVT of the leg and
whose home circumstances are adequate,
recommend initial treatment at home over
treatment in the hospital (1B)
34
Early Ambulation
• In patients with acute DVT of the leg, suggest
early ambulation over initial bed rest (2C)
35
Compression Stockings
• Use in patients with acute symptomatic DVT
of the leg (2B)
– Should be worn for at least 2 years
– Wear beyond if patient develops PTS and finds
stockings helpful
• In patients with PTS of the leg, suggest a trial
of compression stockings (2C)
36
Atrial Fibrillation
Atrial Fibrillation:
Estimating Risk of Ischemic Stroke
CHADS2 Scoring System
Congestive Heart Failure
Hypertension
Age ≥ 75
Diabetes
Stroke or TIA
1 point
1 point
1 point
1 point
2 points
(total of 6 points)
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
38
Dabigatran
• Oral anticoagulation
• Suggest dabigatran 150 mg bid rather than
adjusted-dose vitamin K antagonist therapy
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
39
Dabigatran (Pradaxa®)
• Approved in October 2010
• Indication (U.S.)
• Prevention of stroke and
systemic embolism in patients
diagnosed with Atrial Fibrillation
• Oral capsule, dosed BID and
requires no monitoring
– 75mg & 150mg capsules
PRADAXA® product insert. 2011.
40
Dabigatran (Pradaxa®)
• Dosing
CrCl >30ml/min:
150mg PO BID (+/- food)
CrCl <15-30ml/min:
75mg PO BID (+/- food)
CrCl <15ml/min:
Do not use, no data
• Renal Function*
– Assess prior to initiation
– While treated, re-assess when renal decline is suspected
– When CrCl <50ml/min or age >75, re-assess annually
PRADAXA® product insert. 2011 update.
41
CHADS2 Score of 0
• Low risk of stroke
• Suggest no therapy rather than
antithrombotic therapy
• Patients that choose antithrombotic therapy
– Aspirin rather than oral anticoagulation or
combination therapy with aspirin and clopidogrel
(2B)
• Aspirin 75 mg to 325 mg daily
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
42
CHADS2 Score of 1
• Intermediate risk of stroke
• Oral anticoagulation rather than no therapy
(1B)
• Oral anticoagulation (dabigatran) rather than
aspirin or combination therapy
• Patients unsuitable for or choose not to take
an oral anticoagulant , suggest combination
therapy with aspirin and clopidogrel rather
than aspirin alone
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
43
CHADS2 Score of ≥ 2
• High risk of stroke
• Oral anticoagulation rather than no therapy
(1B)
• Oral anticoagulation (dabigatran) rather than
aspirin or combination therapy
• Patients unsuitable for or choose not to take
an oral anticoagulant , suggest combination
therapy with aspirin and clopidogrel rather
than aspirin alone
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
44
AF and Mitral Stenosis
• Recommend adjusted-dose VKA therapy
(target INR range 2.0-3.0)
• Second line: Combination therapy with aspirin
and clopidogrel (1B)
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
45
AF and Stable Coronary Artery Disease
• Ex: No acute coronary syndrome within the
previous year
• Adjusted-dose VKA therapy alone
– Target INR 2.0-3.0
• Grade 2C
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
46
Post-Stent Placement and CHADS2 ≥ 2
• Triple Therapy (VKA, ASA, and clopidogrel)
– During the first month after placement of a bare-metal
stent (2C)
– First 3 to 6 months after placement of a drug-eluting stent
(2C)
• After initial period of triple therapy, suggest a VKA (INR
2.0-3.0) plus a single antiplatelet drug rather than VKA
alone (2C)
• At 12 months after intracoronary stent placement,
antithrombotic therapy is suggested as for patients
with AF and stable coronary artery disease .
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
47
Post-Stent Placement and CHADS2 0-1
• Dual antiplatelet therapy rather than triple
therapy (2C)
• At 12 months after intracoronary stent
placement, antithrombotic therapy is
suggested as for patients with AF and stable
coronary artery disease
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
48
AF and Acute Coronary Syndrome
• CHADS2 ≥ 1 (intermediate to high risk)
• Do not undergo intracoronary stent placement
• First 12 months
– Adjusted-dose VKA therapy (INR 2.0-3.0) plus
single antiplatelet therapy (eg, aspirin or
clopidogrel) (2C)
• After the first 12 months, see stable coronary
artery disease
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
49
AF and Acute Coronary Syndrome
• CHADS2 = 0 (low risk of stroke)
• Dual antiplatelet therapy (ex., aspirin and
clopidogrel)
• After the first 12 months, antithrombotic
therapy is suggested as for patients with AF
and stable coronary artery disease
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
50
AF being managed with a rhythm
control strategy
• Antithrombotic therapy decisions follow the
general risk-based recommendations for
patients with AF, regardless of the apparent
persistence of normal sinus rhythm (2C)
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
51
Cardioversion
• AF of greater than 48 hours or unknown duration
• Therapeutic anticoagulation for at least 3 weeks
before cardioversion or a transesophageal
echocardiography (TEE) (1B)
– VKA therapy (target 2.0-3.-0)
– LMWH at treatment doses
– Dabigatran
• Therapeutic anticoagulation for at least 4 weeks
after successful cardioversion (1B)
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
52
Cardioversion
• AF of documented duration of 48 hours or less
• Start anticoagulation at presentation and
proceeding to cardioversion (2C)
• After successful cardioversion to sinus rhythm,
therapeutic anticoagulation for at least 4
weeks
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
53
2012 ACCP Guidelines Summary
- ATRIAL FIBRILLATION CHADS2 Score
Treatment Recommendation
Grade
0 (No Risk Factors)
Recommend no therapy, but if choose therapy
suggest aspirin 75-325mg daily alone
2B
1
Preferred: Oral anticoagulation
(1st:Dabigatran 150mg bid, 2nd Warfarin; INR 2-3)
Alternative: aspirin 75-325mg daily plus clopidogrel
1B
>2 or
History of ischemic
stroke or TIA
Preferred: Oral anticoagulation
(1st:Dabigatran 150mg bid, 2nd Warfarin; INR 2-3)
Alternative: aspirin 75-325mg daily plus clopidogrel
1A
Mitral stenosis
Preferred: Warfarin; INR 2-3
Alternative: aspirin 75-325mg daily plus clopidogrel
1B
1B
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
2B
1B
54
2012 ACCP Guidelines Summary
- ATRIAL FIBRILLATION & SPECIAL SITUATIONS CHADS2/Risk factor
Treatment Recommendation
Grade
stable CAD
Warfarin alone (INR 2-3) is preferred over warfarin
plus aspirin
2C
>2 plus bare metal
stent
One month of triple therapy (VKA, ASA,
clopidogrel), then warfarin; INR 2-3 plus single
antiplatelet therapy for 12 months
Thereafter refer to stable CAD recommendations
2C
>2 plus drug-eluting
stent
3 to 6 months of triple therapy (VKA, ASA,
clopidogrel), then warfarin; INR 2-3 plus therapy
antiplatelet for 12 months
Thereafter refer to stable CAD recommendations
2C
0-1 plus any coronary
stent
First 12 months: dual antiplatelet therapy (ASA and
clopidogrel)
Thereafter refer to stable CAD recommendations
2C
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
55
2012 ACCP Guidelines Summary
- ATRIAL FIBRILLATION & SPECIAL SITUATIONS CHADS2/Risk factor
Treatment Recommendation
Grade
0 plus ACS with no
stent placement
First 12 months: dual antiplatelet therapy (ASA and
clopidogrel)
Thereafter refer to stable CAD recommendations
2C
> 1 plus ACS with no
stent placement
First 12 months: warfarin; INR 2-3 plus single
antiplatelet therapy
Thereafter refer to stable CAD recommendations
2C
You, JJ et al. Antithrombotic Therapy in Atrial Fibrillation. Chest. 2012; 141 (suppl 2):e531S-e575S
56
2012 CHEST Guideline Update
VTE prophylaxis, DVT treatment, and Atrial Fibrillation
LT Tabatha Welker, PharmD
Pharmacy Resident, PHS Claremore Indian Hospital