Prevention and Treatment of
Venous Thromboembolism
National Performance Measures And Recent
Guidelines
Dale W. Bratzler, DO, MPH
Professor and Associate Dean, College of Public Health
Professor of Medicine, College of Medicine
Chief Quality Officer – OU Physicians Group
University of Oklahoma Health Sciences Center
Dale W. Bratzler, DO, MPH
QIOSCAugust
Medical
Director
3, 2012
Outline
• The problem – VTE in US hospitals
• Need for national performance standards
• Update on National Guidelines for Prevention
of VTE
• Strategies for prevention of VTE
2
Venous thromboembolism (VTE) =
Deep vein thrombosis (DVT) and
Pulmonary embolism (PE)
“The best estimates indicate
that 350,000 to 600,000
Americans each year suffer
from DVT and PE, and that at
least 100,000 deaths may be
directly or indirectly related to
these diseases. This is far too
many, since many of these
deaths can be avoided.
Because the disease
disproportionately affects
older Americans, we can
expect more suffering and
more deaths in the future as
our population ages–unless
we do something about it.”
Annual Incidence of VTE in Olmsted County,
MN: 1966-1995
1,200
Men
1,000
800
600
Women
400
200
Age group (yr)
85
0
014
15
-1
20 9
-2
25 4
-2
30 9
-3
35 4
-3
40 9
-4
45 4
-4
50 9
-5
55 4
-5
60 9
-6
65 4
-6
70 9
-7
75 4
-7
80 9
-8
4
Annual incidence/100,000
By Age and Gender
5
Prevention of Venous Thromboembolism
Introduction
• VTE Remains a major health problem
– In addition to the risk of sudden death
• 30% of survivors develop recurrent VTE within
10 years
• 28% of survivors develop venous stasis
syndrome within 20 years
Goldhaber SZ. N Engl J Med. 1998;339:93-104.
Silverstein MD, et al. Arch Intern Med. 1998;158:585-593.
Heit JA, et al. Thromb Haemost. 2001;86:452-463.
Heit JA. Clin Geriatr Med. 2001;17:71-92.
Heit JA, et al. Mayo Clin Proc. 2001;76:1102-1110.
6
Risk of DVT in Hospitalized Patients
No prophylaxis + routine objective screening for DVT
Patient group
DVT incidence
Medical patients
10 - 20 %
Major gyne/urol/gen surgery
15 - 40 %
Neurosurgery
15 - 40 %
Stroke
20 - 50 %
Hip/knee surgery
40 - 60 %
Major trauma
40 - 80 %
Spinal cord injury
60 - 80 %
Critical care patients
15 - 80 %
7
Associated Illnesses that are a
Consequence of VTE events
• Chronic thromboembolic pulmonary
hypertension
– Mean pulmonary artery pressure greater than 25
mm Hg that persists 6 months after PE
– 2-4% of patients after PE
• Post-thrombotic syndrome
– Calf swelling and skin pigmentation; venous
ulceration in severe cases
• Up to 43% of patients within 2 years – most mild
Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.
Prevention of Venous Thromboembolism
• The majority (93%) of estimated VTE-related
deaths in the US were due to sudden, fatal PE
(34%) or followed undiagnosed VTE (59%)
For many patients, the first symptom of VTE is
sudden death!
How many of those patients with sudden death in the
hospital or after discharge attributed to an acute coronary
event actually died of acute pulmonary embolism?
Heit JA, Cohen AT, Anderson FA on behalf of the VTE Impact Assessment Group.
[Abstract] American Society of Hematology Annual Meeting, 2005.
9
National Body Position Statements
• Leapfrog1:
PE is “the most common preventable cause of hospital death in
the United States”
• Agency for Healthcare Research and Quality (AHRQ)2:
Thromboprophylaxis is the number 1 patient safety practice
• American Public Health Association (APHA)3:
“The disconnect between evidence and execution as it relates
to DVT prevention amounts to a public health crisis.”
The Leapfrog Group Hospital Quality and Safety Survey. Available at: www.leapfrog.medstat.com/pdf/Final/doc
Shojania KG, et al. Making Healthcare Safer: A Critical Analysis of Patient Safety Practices. AHRQ, 2001.
Available at: www.ahrq.gov/clinic/ptsafety/
White Paper. Deep-vein thrombosis: Advancing awareness to protect patient lives. 2003. Available at:
www.alpha.org/ppp/DVT_White_Paper.pdf
10
Annual cost to treat VTE
• $11,000 per DVT episode per patient
• $17,000 per PE episode per patient
• Recurrence increases hospitalization costs by
20%
• Complications of anticoagulation
• Time lost from work
– Quality of life: venous stasis and pulmonary HTN
11
Consequences of Surgical Complications
• Dimick and colleagues demonstrated increased costs
of care:
–
–
–
–
infectious complications was $1,398
cardiovascular complications $7,789
respiratory complications $52,466
thromboembolic complications $18,310
Dimick JB, et al. J Am Coll Surg 2004;199:531-7.
12
Do venous and arterial diseases have
shared risk factors?
“…..4 years after surviving
a PE, fewer than half will remain
free of MI, stroke, PAD, recurrent
VTE, cancer or chronic
thromboembolic pulmonary
hypertension.”
VTE and atherothrombosis have
a common pathophysiology that
includes inflammation,
hypercoagulability, and
endothelial injury.
Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.
Inherited risk factors for DVT
Group 1 disorders
Group 2 disorders
• Protein C deficiency (2.5-6%)
• Protein S deficiency (1.3-5%)
• Antithrombin deficiency (0.57.5%)
• Factor V leiden (6%)
• Prothrombin (G20210A) (510%)
• Elevated VIII, IX, XI
• Hyperhomocysteinemia
• Arteriosclerosis
14
Acquired Risk Factors
Risk Factor
Attributable Risk
Hospitalization/Nursing home
61.2
Active malignant neoplasm
19.8
Trauma
12.5
CHF
11.8
CV catheter
10.5
Neurologic disease with paresis
8.2
Superficial vein thrombosis
4.3
Varicose veins/stripping
6
Many others….
Being in the hospital is the greatest risk factor for VTE!
15
Risk Factors for DVT or PE
Nested Case-Control Study (n=625 case-control pairs)
Surgery
Trauma
Inpatient
Malignancy with chemotherapy
Malignancy without chemotherapy
Central venous catheter or pacemaker
Neurologic disease
Superficial vein thrombosis
Varicose veins/age 45 yr
Varicose veins/age 60 yr
Varicose veins/age 70 yr
CHF, VTE incidental on autopsy
CHF, antemortem VTE/causal for death
Liver disease
0
5
10
15
20
25
50
Odds ratio
16
Independent Risk Factors for VTE after
Major Surgery*:
Olmsted County 1988-97 (n=163)
Risk Factor
OR
95% CI
P-value
Age (per 10 years)
1.26
1.07, 1.50
0.007
BMI (kg/m2, per 2-fold increase)
2.95
1.49, 5.82
0.002
ICU Length of Stay > 6 Days
3.97
1.46, 10.80
0.007
Central Venous Catheter
2.46
1.21, 5.03
0.013
Immobility Requiring Physical
Therapy
2.18
1.17, 4.06
0.014
Varicose Veins
1.87
1.08, 3.23
0.025
Any Infection
1.68
1.01, 2.82
0.046
Anticoagulation Prophylaxis
0.27
0.12, 0.59
0.001
*Controlled for Surgery Type, Active Cancer, and Event Year
Heit, et al. J Thromb Haemost 2005
17
Cases per 10,000 person-years
VTE is a Disease of Hospitalized and
Recently Hospitalized Patients
1000
VTE 100X more common in
hospitalized patients!
100
Recently
hospitalized
10
1
Hospitalized patients
Community residents
Heit JA. Mayo Clin Proc. 2001;76:1102
18
Cumulative Incidence of VTE After Primary Hip
or Knee Replacement
3.5
Primary hip
Primary knee
3.0
2.5
VTE
events
(%)
2.0
1.5
1.0
0.5
0.0
0
7
14
21
28
35
42
49
56
63
70
77
84
91
Days
White RH, et al. Arch Intern Med. 1998; 158: 1525-1531
19
Many events occur after hospital
discharge.
• IMPROVE Registry
– 15,156 medical patients admitted to the hospital
• 184 patients had VTE events
– 45% developed VTE after discharge
• Other studies have shown that up to twothirds of VTE events occur in patients after
discharge
Spyropoulos AC, et al. Chest 2011; 140:706-14.
VTE Facts
• Almost half of the
outpatients with VTE had
been recently hospitalized
• About half had a length
of stay (LOS) of < 4 days
0-29
Outpatients With VTE, %
• Less than half of the
recently hospitalized
patients had received VTE
prophylaxis during their
hospitalizations
Days After Discharge
30-59
60-90
70
60
50
40
30
20
10
0
Medical
Hospitalization
Only
Hospitalization
with Surgery
Goldhaber S. Arch Intern Med. 2007;167:1451-2.
Spencer FA et al. Arch Intern Med. 2007;167(14):1471-5.
Prevention of Venous Thromboembolism
• Despite the well known risk of VTE and the
publication of evidence-based guidelines for
prevention, multiple medical record audits
have demonstrated underuse of prophylaxis
Anderson FA Jr, et al. Ann Intern Med. 1991;115:591-595.
Anderson FA Jr, et al. J Thromb Thrombolysis. 1998; 5 (1 Suppl):7S-11S.
Bratzler DW, et al. Arch Intern Med. 1998;158:1909-1912.
Stratton MA, et al. Arch Intern Med. 2000;160:334-340.
22
Published Audits of VTE Prophylaxis
General Surgery
Received Prophylaxis
No Prophylaxis
280
97/250 (39%)
240
Cases
200
160
120
30/86 (35%)
33/83 (40%)
Moderate
High
80
40
0
Very High
Use of any form of prophylaxis based on level of risk for venous thromboembolism among 419 Medicare patients from
20 hospitals undergoing major abdominothoracic surgery. Measures were implemented for patients at moderate risk
(35%; 95% CI, 25-46%), at high risk (40%; 95% CI, 29-51%), and at very high risk (39%; 95% CI, 33-45%). Overall
utilization rate for prophylaxis was 38% (95% CI, 33-43%).
Bratzler DW, et al. Arch Intern Med. 1998;158:1909-1912.
Thromboprophylaxis Use in Practice
1992-2002
Patient Group
Studies
Patients
Prophylaxis
Use (any)
Orthopedic surgery
4
20,216
90 % (57-98)
General surgery
7
2,473
73 % (38-98)
Critical care
14
3,654
69 % (33-100)
Gynecology
1
456
Medical patients
5
1,010
66 %
23 % (14-62)
How many patients with COPD, CVA, heart failure, pneumonia, etc
do you have in your hospital that are not on DVT prophylaxis?
24
Prevention of VTE in Medical Patients
Amin A, Stemkowski S, Lin J, Yang G. J Thromb Haemost 2007; 5: 1610–6.
Prevention of VTE in Medical Patients
Amin A, Stemkowski S, Lin J, Yang G. J Thromb Haemost 2007; 5: 1610–6.
Diagnosis of VTE
• D-dimer (rule out
only)
• Compression
ultrasound
• CT angiography
Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.
Diagnosis of VTE
Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379:1835-46.
Prophylaxis and Treatment
Prophylaxis Modalities
• Mechanical
– Graduated compression stockings (GCS) (e.g., “white
hose”)
– Sequential compression devices
• Venous foot pumps (currently recommended only for orthopedic
surgery in patients with bleeding risk)
In most studies, less effective than pharmacologic
prophylaxis and patient compliance rates are
generally low.
Rates of compliance with mechanical forms of prophylaxis in many studies is
less than 50% - has become a new target of malpractice litigation.
30
Pharmacologic Prophylaxis
•
•
•
•
Low-dose unfractionated heparin (LDUH)
Low-molecular weight heparin (LMWH)*
Fondaparinux*
Direct inhibitors of activated factor X
– rivaroxaban
• Direct thrombin inhibitors
– dabigatran
• Warfarin
• Aspirin
*Cleared by the kidneys.
31
Approach to Treatment
How long do you treat?
Duration of Treatment
Evidence
Grade
First VTE event secondary to a
reversible factor (“provoked”)
3 months
1A
First idiopathic (“unprovoked) VTE
At the end of initial 3-month period
In the absence of contraindication
During long-term treatment
At least 3 months
Assess for long-term Rx
Long-term Rx
Assess risk/benefit balance
1A
1C
1A
1C
Recurrent VTE or strong thrombophilia Long-term Rx
1A
VTE secondary to cancer
1A
1C
Long-term Rx, preferentially
with LMWH during the first 36 months, then anticoagulate
as long as the cancer is
considered “active”
Kearon C, et al. Chest 2008; 133 (6 suppl):454S-545S.
Do we have to use warfarin longterm?
Multicenter, double-blind
study, patients with firstever unprovoked venous
thromboembolism who
had completed 6 to 18
months of oral
anticoagulant treatment
were randomly assigned
to aspirin, 100 mg daily,
or placebo for 2 years
Becattini C, et al. N Engl J Med 2012;366:1959-67.
Development of National Performance
Measures to Prevent and Treat VTE
35
Why the need for performance measures?
• Despite widespread publication and
dissemination of guidelines, practices have
not changed at an acceptable pace
– There are still far too many needless deaths from
VTE in the US
• Reasonably good evidence that using
performance measures for accountability can
accelerate the rate of change
36
37
Venous Thromboembolism
Statement of Organization Policy
“Every healthcare facility shall have a written policy
appropriate for its scope, that is evidence-based and
that drives continuous quality improvement related to
VTE risk assessment, prophylaxis, diagnosis, and
treatment.”
38
Venous Thromboembolism
Characteristics of Preferred Practices
General
• Protocol selection by multidisciplinary teams
• System for ongoing QI
• Provision for RA/stratification, prophylaxis,
diagnosis, treatment
• QI activity for all phases of care
• Provider education
39
Venous Thromboembolism
Characteristics of Preferred Practices
(cont.)
Risk Assessment/Stratification
• RA on all patients using evidence-based policy
• Documentation in patient record that done
Prophylaxis
• Based on assessment & risk/benefit, efficacy/safety
• Based on formal RA, consistent with accepted,
evidence-based guidelines
40
Venous Thromboembolism
Characteristics of Preferred Practices
(cont.)
Diagnosis
• Objective testing to justify continued initial therapy
Treatment and Monitoring
•
•
•
•
•
Ensure safe anticoagulation, consider setting
Incorporate Safe Practice 29
Patient education; consider setting and reading levels
Guideline-directed therapy
Address care setting transitions in therapy
41
Surgical Care Improvement Project
First Two VTE Measures Endorsed by NQF
• Prevention of venous thromboembolism
• Proportion who have recommended VTE
prophylaxis ordered
• Proportion who receive appropriate form of VTE
prophylaxis (based on ACCP Consensus
Recommendations) within 24 hours before or
after surgery
42
Venous Thromboembolism
Technical Advisory Panel (TAP) charge
• Vet the 19 potential measures, agreed upon by the
Steering Committee, through TAP and The Joint
Commission survey processes
• Identify a subset of measures that help address the
identified gaps within the endorsed VTE domains
• Oversee final development and testing of measures for
Steering Committee and NQF endorsement
consideration
43
6 Refined Measures That Were Endorsed
 Risk Assessment/Prophylaxis domain
 Prophylaxis w/in 24 hours of admission or surgery,
OR a documented risk assessment showing that the
patient does not need prophylaxis
 Prophylaxis/documentation w/in 24 hours after ICU
admission or surgery
44
6 Refined Measures That Were Endorsed
 Patients w/overlap of anticoagulation therapy
 At least five calendar days of overlap and discharge with INR
> 2.0, or discharge on overlap therapy
 Patient receiving UFH with dosage/platelet count
monitoring by protocol/nomogram
 Nomogram/protocol incorporates routine platelet count
monitoring
45
6 Refined Measures Endorsed (cont.)
 Treatment/Monitoring Domain (cont.)
– Discharge instructions consistent with Joint Commission safety
goals (Follow-up Monitoring, Compliance Issues, Dietary
Restrictions, Potential for Adverse Drug Reactions/Interactions)
 Outcome
 Incidence of potentially-preventable VTE – proportion of
patients with hospital-acquired VTE who had NOT received VTE
prophylaxis prior to the event
46
New Guidelines and Controversies
New Guidelines
http://www.chestnet.org/accp/guidelines/accp-antithrombotic-guidelines-9th-ed-now-available
ACCP Disclaimer
The ACCP recommends that performance measures for quality
improvement, performance-based reimbursement, and public
reporting purposes should be based on rigorously developed
guideline recommendations. However, not all recommendations
graded highly according to the ACCP grading system (1A, 1B)
are necessarily appropriate for development into such
performance measures, and each one should be analyzed
individually for importance, feasibility, usability, and scientific
acceptability (National Quality Forum criteria). Performance
measures developers should exercise caution in basing
measures on recommendations that are graded 1C, 2A, 2B, and
2C, according to the ACCP Grading System1 as these should
generally not be used in performance measures for quality
improvement, performance-based reimbursement, and public
reporting purposes.
ACCP 9th Edition
General Overview
• For acutely ill hospitalized medical patients at
increased risk of thrombosis, we recommend
anticoagulant thromboprophylaxis with
LMWH, LDUH, or fondaparinux (Grade 1B)
– Mechanical prophylaxis (GCS or IPC) if bleeding or
high risk for bleeding
• Similar recommendation for critically ill
patients
ACCP 9th Edition
General Overview
• For patients undergoing non-orthopedic
surgery
– Generally recommend the use of a risk
assessment tool (Rogers score or Caprini score) to
determine need for prophylaxis
• Low risk of VTE (Rogers score < 7.0, Caprini score 0) no
prophylaxis recommended other than early ambulation
Bahl V, et al. Ann Surg. 2010; 251:344-50.
Bahl V, et al. Ann Surg. 2010; 251:344-50.
Rogers SO, et al. J Am Coll Surg 2007;204:1211–1221.
Rogers SO, et al. J Am Coll Surg 2007;204:1211–1221.
ACCP 9th Edition
General Overview
• Patients undergoing major orthopedic surgery
(THA, TKA, or HFS) recommend LMWH,
fondaparinux, apixaban, dabigatran,
rivaroxaban, LDUH, adjusted-dose warfarin,
aspirin (all Grade 1B), or an IPC device (Grade
1C).
– Subsequently recommend in THA, TKA, or HFS
LMWH the preferred agent (Grade 2B)
ACCP Guidelines
• The technical expert panel is evaluating new
guidelines to consider revisions
– No revisions likely before January 2014
– Many of the recommendations in guidelines do
not have 1A and 1B grades and remain very
controversial
– Most hospitalized patients have additional risk
factors for VTE
Strategies for Improvement
59
Strategies to Improve VTE Prophylaxis
• Hospital policy of risk assessment or routine
prophylaxis for all admitted patients
– Most will have risk factors for VTE and should
receive prophylaxis
– Preprinted protocols for surgical patients
60
Electronic Alerts to Prevent VTE among
Hospitalized Patients
• Hospital computer system identified patient VTE risk factors
• RCT: no physician alert vs physician alert
No.
Any prophylaxis
VTE at 90 days
Major bleeding
Control
group
1,251
15 %
8.2 % *
1.5 %
Alert
group
P
1,255
34 % <0.001
4.9 %
0.001
1.5 %
NS
Kucher – N Engl J Med 2005;352:969
61
Electronic Alerts to Prevent VTE among
Hospitalized Patients
• Among hospitalized patients with risk
factors for VTE and not receiving
prophylaxis, use of a physician VTE risk
alert:
– Improved use of prophylaxis by 130%
– Reduced symptomatic VTE by 41%
– Did not increase bleeding
Kucher – N Engl J Med 2005;352:969
62
Improving Compliance with
Treatment Protocols
• Use of standardized protocols, nomograms,
algorithms, or preprinted orders
– Address overlap (either 5 days in hospital or
discharge on overlap)
– When used, UFH should be managed by
nomogram/protocol, and the protocol should
ensure routine platelet count monitoring
Essential Elements for Improvement
• Institutional support
• A multidisciplinary team or steering committee
• Reliable data collection and performance tracking
• Specific goals or aims
• A proven QI framework
• Protocols
SHM Resource Room. http://www.hospitalmedicine.org. Accessed September 2009.
Risk
Assessment
Prophylaxis
Low
Ambulatory patient without VTE risk
factors; observation patient with expected
LOS 2 days; same day surgery or minor
surgery
Early ambulation
Moderate
All other patients (not in low-risk or highrisk category); most medical/surgical
patients; respiratory insufficiency, heart
failure, acute infectious, or inflammatory
disease
UFH 5000 units SC q 8
hours; OR LMWH q day; OR
UFH 5000 units SC q 12
hours (if weight < 50 kg or
age > 75 years); AND
suggest adding IPC
High
Lower extremity arthroplasty; hip, pelvic,
or severe lower extremity fractures; acute
SCI with paresis; multiple major trauma;
abdominal or pelvic surgery for cancer
LMWH (UFH if ESRD); OR
fondaparinux 2.5 mg SC
daily; OR warfarin, INR 2-3;
AND IPC (unless not
feasible)
Maynard GA, et al. J Hosp Med 2009 Sep 14. [Epub ahead of print]
Maynard GA, et al. J Hosp Med 2009 Sep 14. [Epub ahead of print]
Conclusions
• VTE remains a substantial health problem in
the US
• VTE prophylaxis remains underutilized
• National performance measures may address
both prophylaxis and treatment of VTE across
broad hospital populations
67
dale-bratzler@ouhsc.edu