Venous Thromboembolism Prophylaxis in Orthopedic Surgery

1
Venous Thromboembolism Prophylaxis in Orthopedic
Surgery

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

2
Outline of This Presentation

• The comparative effectiveness review (CER)
  process
• Overview of venous thromboembolism (VTE) and
  orthopedic surgery
• VTE prophylaxis
• Results from the CER
• Summary of conclusions
• Gaps in knowledge
• What to discuss with your patients

3
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development

• Topics are nominated through a public process,
  which includes submissions from health care
  professionals, professional organizations, the
  private sector, policymakers, the public, and
  others.
• A systematic review of all relevant clinical
  studies is conducted by independent researchers,
  funded by AHRQ, to synthesize the evidence in a
  report summarizing what is known and not known
  about the select clinical issue. The research
  questions and the results of the report are
  subject to expert input, peer review, and public
  comment.
• The results of these reviews are summarized into
  Clinician and Consumer Research Summaries for use
  in decisionmaking and in discussions with
  patients. The research reviews and the full
  report are available at www.effectivehealthcare.ah
  rq.gov/thrombo.cfm.

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
4
Rating the Strength of Evidence From the
Comparative Effectiveness Review

• The strength of evidence was classified into four
  broad categories

High There is high confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.
Moderate Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate.
Low Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of effect and is likely to change the estimate.
Insufficient Evidence either is unavailable or does not permit estimation of an effect.
AHRQ. Methods Guide for Effectiveness and
Comparative Effectiveness Reviews. April 2012.
Available at www.effectivehealthcare.ahrq.gov/ehc/
products/60/318/MethodsGuide_Prepublication-Draft
_20120409.pdf. Sobieraj DM, Coleman CI, Tongbram
V, et al. Comparative Effectiveness Review No.
49. Available at www.effectivehealthcare.ahrq.gov/
thrombo.cfm.
5
Thromboprophylaxis in Major Orthopedic Surgery

• Major orthopedic surgery including total hip
  replacement (THR), total knee replacement (TKR),
  and hip fracture surgery carries a risk for
  venous thromboembolism (VTE).
• Without prophylaxis, historic data suggest deep
  vein thrombosis (DVT) occurs in 4060 percent of
  cases in the 714 days following surgery.
• With routine use of thromboprophylaxis,
  symptomatic VTE in patients within 3 months of
  surgery is approximately 1.310 percent.
• Prophylactic strategies may decrease the risk of
  VTE, DVT, and pulmonary embolism.
• The main limitation of pharmacological VTE
  prophylaxis is the risk of bleeding, which
  historically occurs in 13 percent of THR and TKR
  surgeries.

American Academy of Orthopaedic Surgeons.
Guideline on preventing venous thromboembolic
disease in patients undergoing elective hip and
knee arthroplasty. Available at
www.aaos.org/research/guidelines/VTE/VTE_guideline
.asp.
6
Preventing Venous Thromboembolic Events in Major
Orthopedic Surgery

• A variety of strategies to prevent venous
  thromboembolism are available
• Pharmacological
• Oral antiplatelet agents
• Injectable low-molecular-weight heparins
• Injectable unfractionated heparin
• Injectable or oral factor Xa inhibitors
• Injectable or oral direct thrombin inhibitors
• Oral vitamin K antagonists
• Mechanical modalities
• Graduated compression
• Intermittent pneumatic compression
• Venous foot pump
• Combinations of these

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
7
Establishing the Need for a Systematic Review of
VTE Prophylaxis in Orthopedic Surgery

• The magnitude of benefit and harms in
  contemporary practice and evaluation of
  pharmacological agents or devices available
  within the United States amongst the orthopedic
  surgery population is not well known.
• Additionally, the influence of these factors in
  contemporary practice needs to be systematically
  evaluated
• The impact of duration of prophylaxis on outcomes
• Whether dual prophylactic therapy is superior to
  single-modality therapy
• The comparative effectiveness of different
  pharmacological or mechanical modalities
• The risks of VTE, PE, and DVT and the causal link
  between DVT and PE.

American Academy of Orthopaedic Surgeons.
Guideline on preventing venous thromboembolic
disease in patients undergoing elective hip and
knee arthroplasty. Available at
www.aaos.org/research/guidelines/VTE/VTE_guideline
.asp.
8
Baseline Postoperative Risk of Venous
Thromboembolism and Bleeding Outcomes in
Contemporary Practice
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
9
Baseline Postoperative Risks of VTE Outcomes in
the Absence of Pharmacological Prophylaxis

• Most of the literature evaluated total hip and
  total knee replacement surgeries with very little
  evaluation of hip fracture surgery. The baseline
  risk of venous thromboembolism and bleeding
  outcomes in the absence of pharmacological
  prophylaxis are as follows

Outcome Total Hip Replacement Strength of Evidence(THR) Total Knee Replacement Strength of Evidence(TKR)
Pulmonary embolism 6 Low 1 Low
Deep vein thrombosis 39 Low 46 Low
Major bleeding 1 Moderate 3 Low
Minor bleeding 5 Low 5 Moderate
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
10
Comparative Effectiveness of Pharmacological or
Mechanical Thromboprophylaxis Versus No
Thromboprophylaxis

• Pharmacological versus no pharmacological
  prophylaxis
• Mechanical versus no thromboprophylaxis

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
11
Comparative Effectiveness of Pharmacological
Prophylaxis Versus No Pharmacological Prophylaxis
Outcome Magnitude of Effect RR/OR (95 CI), NNT/NNH Strength of Evidence
DVT Decreases risk by 44 RR 0.56 (0.47 to 0.68), NNT 3 to 33 Moderate
Proximal DVT Decreased risk by 47 RR 0.53 (0.39 to 0.74), NNT 4 to 213 High
Distal DVT Decreased risk by 41 RR 0.59 (0.42 to 0.82),NNT 8 to 35 High
Asymptomatic DVT Decreased risk by 48 RR 0.52 (0.40 to 0.69),NNT 4 to 6 Moderate
Symptomatic VTE NR
Major VTE Decreased risk by 79 RR 0.21 (0.05 to 0.95),NNT 19 to 22 Low
PE No difference OR 0.38 (0.13 to 1.07) Low
Abbreviations 95 CI 95-percent confidence
interval NNH number needed to harm (the
calculated range) NNT number needed to treat
(the calculated range NR not reported or
insufficient evidence to permit conclusions OR
odds ratio RR relative risk
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
12
Comparative Effectiveness of Pharmacological
Prophylaxis Versus No Pharmacological
Prophylaxis Adverse Effects
Outcome Magnitude of Effect RR/OR (95 CI), NNT/NNH Strength of Evidence
Major Bleeding No difference RR 0.74 (0.36 to 1.51) Moderate
Minor Bleeding Relative risk is higher for pharmacological prophylaxis by 67 RR 1.67 (1.18 to 2.38),NNH 30 to 75 High
Abbreviations 95 CI 95-percent confidence
interval NNH number needed to harm NNT
number needed to treat OR odds ratio RR
relative risk
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
13
Comparative Effectiveness of Mechanical
Prophylaxis Versus No Thromboprophylaxis

• Mechanical prophylaxis significantly decreased
  deep vein thrombosis (DVT results from one
  randomized controlled trial strength of evidence
  not rated).
• The risk for proximal or distal DVT was not
  significantly different (results from one
  randomized controlled trial strength of evidence
  not rated).
• Data are not available to evaluate the
  comparative effect of mechanical prophylaxis
  versus no prophylaxis on other outcomes.

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
14
Comparative Effectiveness of Pharmacological and
Mechanical Prophylaxis Agents
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
15
Comparative Effectiveness of Pharmacological
Prophylaxis Agents LMWH Versus UFH
Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE)
Comparators DVT Proximal DVT Symptomatic VTE PE Major Bleeding Minor Bleeding Heparin-induced Thrombo-cytopenia
LMWH vs. UFH Decreased risk by 20 RR 0.80 (0.65 to 0.99), NNT 12 to 100 (SOE Moderate) Decreased risk by 40 RR 0.60 (0.38 to 0.93), NNT 14 to 50 (SOE High) NR Decreased odds by 52 OR 0.48 (0.24 to 0.95), NNT 8(SOE Moderate) Decreased odds by 35 OR 0.57 (0.37 to 0.88), NNT 41(SOE High) No differenceRR 0.90 (0.63 to 1.28) (SOE Moderate) Decreased odds by 88 OR 0.12 (0.03 to 0.43), NNT 34 to 202(SOE Moderate)
Abbreviations 95 CI 95-percent confidence
interval DVT deep vein thrombosis LMWH
low-molecular-weight heparin major bleeding
for example, bleeding leading to greater
transfusion requirements and/or reoperation
minor bleeding for example, surgical site
bleeding, bleeding leading to infection, or
bleeding leading to transfusion but not
reoperation NNH number needed to harm (the
calculated range) NNT number needed to treat
(the calculated range) NR not reported or
insufficient evidence to permit conclusions OR
odds ratio PE pulmonary embolism RR
relative risk SOE strength of evidence rating
UFH unfractionated heparin VTE venous
thromboembolism
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
16
Comparative Effectiveness of Pharmacological
Prophylaxis Agents Enoxaparin Versus Fondaparinux
Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE)
Comparators DVT Proximal DVT Symptomatic VTE PE Major Bleeding Minor Bleeding
Enoxaparinvs. fondaparinux Relative risk is higher for enoxaparinby 99RR 1.99 (1.57 to 2.51), NNH 13 to 26(SOE Moderate) Odds are higher for enoxaparin by 219OR 2.19(1.52 to 3.16), NNH 44 to 122 (SOE Low) No difference OR 0.70(0.48 to 1.02) (SOE Low) No difference OR 3.34 (0.58 to 19.32) (Not rated) Decreased odds by 35OR 0.65 (0.48 to 0.89),NNT 74 to 145 (SOE Moderate) Decreased odds by 43 OR 0.57 (0.35 to 0.94), NNT 31 to 60 (SOE Low)
Abbreviations 95 CI 95-percent confidence
interval DVT deep vein thrombosis major
bleeding for example, bleeding leading to
greater transfusion requirements and/or
reoperation minor bleeding for example,
surgical site bleeding, bleeding leading to
infection, or bleeding leading to transfusion but
not reoperation NNH number needed to harm (the
calculated range) NNT number needed to treat
(the calculated range) OR odds ratio PE
pulmonary embolism RR relative risk SOE
strength of evidence rating VTE venous
thromboembolism
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
17
Comparative Effectiveness of Pharmacological
Prophylaxis Agents LMWH Versus Warfarin
Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE)
Comparators DVT Proximal DVT SymptomaticVTE PE Major Bleeding Minor Bleeding
LMWH vs. warfarin Decreased risk by 34 RR 0.66(0.55 to 0.79), NNT 6 to 13 (SOE Low) No difference RR 0.63(0.39 to 1.00)(SOE Low) No difference OR 1.00 (0.69 to 1.46) (SOE Low) No differenceOR 1.11 (0.57 to 2.19) (SOE Moderate) Odds are higher for LMWH by 92OR 1.92(1.27 to 2.91), NNH 57 to 220(SOE High) Relative risk is higher for LMWHby 23 RR 1.23(1.06 to 1.43), NNH 18 to 218 (SOE Moderate)
Abbreviations 95 CI 95-percent confidence
interval DVT deep vein thrombosis LMWH
low-molecular-weight heparin major bleeding
for example, bleeding leading to greater
transfusion requirements and/or reoperation
minor bleeding for example, surgical site
bleeding, bleeding leading to infection, or
bleeding leading to transfusion but not
reoperation NNH number needed to harm (the
calculated range) NNT number needed to treat
(the calculated range) OR odds ratio PE
pulmonary embolism RR relative risk SOE
strength of evidence rating VTE venous
thromboembolism
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
18
Comparative Effectiveness of Pharmacological
Prophylaxis Agents UFH Versus Desirudin
Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE) Magnitude of Effect Risk/Odds (95 CI), NNT/NNH (SOE)
Comparators DVT Proximal DVT SymptomaticVTE PE Major Bleeding Minor Bleeding
UFH vs. desirudin Relative risk is higher for UFH by 231RR 2.31 (1.34 to 4.00), NNH 5 to 11 (SOE Moderate) Odds are higher for UFH by 477 OR 4.74 (2.99 to 7.49), NNH 11 (SOE Moderate) NR No difference OR 3.23 (0.56 to 18.98)(SOE Low) NR NR
Abbreviations 95 CI 95-percent confidence
interval DVT deep vein thrombosis major
bleeding for example, bleeding leading to
greater transfusion requirements and/or
reoperation minor bleeding for example,
surgical site bleeding, bleeding leading to
infection, or bleeding leading to transfusion but
not reoperation NNH number needed to harm (the
calculated range) NR not reported or
insufficient evidence to permit conclusions OR
odds ratio PE pulmonary embolism RR
relative risk SOE strength of evidence rating
UFH unfractionated heparin VTE venous
thromboembolism
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
19
Comparative Effectiveness of Pharmacological and
Mechanical Prophylaxis

• Warfarin decreased the risk of proximal deep vein
  thrombosis (DVT) by 63 percent when compared with
  mechanical prophylaxis.
• Strength of Evidence Moderate
• Patients on aspirin had higher rates of DVT when
  compared with those using only mechanical
  prophylaxis.
• Strength of Evidence Moderate
• Pharmacological plus mechanical prophylaxis
  reduced the risk of DVT by 52 percent when
  compared with pharmacological prophylaxis alone.
• Strength of Evidence Moderate

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
20
Comparative Effectiveness of Prolonged (28 Days)
Versus Standard (710 Days) Pharmacological
Prophylaxis
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
21
Prolonged (28 Days) Versus Standard (710 Days)
Pharmacological Prophylaxis Clinical Outcomes
Prolonged Versus Standard-Duration Prophylaxis Magnitude of Effect Risk/Odds (95 CI) NNT/NNH Strength of Evidence
Symptomatic VTE Decreased risk by 62 RR 0.38 (0.19 to 0.77) NNT 8 to 54 Moderate
PE Decreased odds by 87 OR 0.13 (0.04 to 0.47) NNT 24 to 232 High
Nonfatal PE Decreased odds by 87 OR 0.13 (0.03 to 0.54) NNT 58 Moderate
DVT Decreased risk by 63 RR 0.37 (0.21 to 0.64) NNT 5 to 32 Moderate
Asymptomatic DVT Decreased risk by 52 RR 0.48 (0.31 to 0.75) NNT 8 to 65 High
Symptomatic DVT Decreased odds by 64 OR 0.36 (0.16 to 0.81) NNT 27 to 79 High
Proximal DVT Decreased risk by 71 RR 0.29 (0.16 to 0.52) NNT 9 to 71 High
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
22
Prolonged (28 Days) Versus Standard (710 Days)
Pharmacological Prophylaxis Adverse Effects
Prolonged Versus Standard-Duration Prophylaxis Magnitude of Effect Risk/Odds (95 CI) NNT/NNH Strength of Evidence
Major Bleeding No difference OR 2.18 (0.73 to 6.51) Low
Minor Bleeding Odds are higher for prolonged prophylaxis by 244 OR 2.44 (1.41 to 4.20) NNH 11 to 118 High
Abbreviations 95 CI 95-percent confidence
interval major bleeding for example, bleeding
leading to greater transfusion requirements
and/or reoperation minor bleeding for example,
surgical site bleeding, bleeding leading to
infection, or bleeding leading to transfusion but
not reoperation NNH number needed to harm (the
calculated range) NNT number needed to treat
(the calculated range) OR odds ratio
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
23
Patient or Surgical Characteristics That May
Affect the Risk ofVenous Thromboembolism
Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
24
Characteristics That May Affect Risk of Venous
Thromboembolism Results

• Patients who receive general anesthesia may have
  a higher risk of deep vein thrombosis (DVT) than
  those who receive regional anesthesia however,
  there were no differences in proximal or
  symptomatic DVT.
• Strength of Evidence Low
• No difference in risk of DVT or proximal DVT was
  found among patients receiving cemented versus
  noncemented arthroplasty.
• Strength of Evidence Low
• Observational data suggest that patients with
  congestive heart failure were at an increased
  risk for symptomatic, objectively confirmed
  venous thromboembolism when compared with those
  without it.
• Strength of Evidence Moderate

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
25
Summary of the RECORD Trials

• The oral direct factor Xa inhibitor, rivaroxaban,
  was approved by the FDA for preventing DVT, which
  may be associated with PE, in patients undergoing
  THR or TKR surgery.
• This decision was based, in part, on the findings
  of four phase III trials known as the Regulation
  of Coagulation in Orthopedic Surgery to Prevent
  Deep Venous Thrombosis and Pulmonary Embolism
  (RECORD) trials RECORD 1, RECORD 2, RECORD 3,
  and RECORD 4.
• They compared various regimens of rivaroxaban and
  enoxaparin in THR or TKR surgery.
• The primary efficacy outcome was composite DVT,
  nonfatal PE, or all-cause mortality.
• The primary safety outcome was major bleeding.

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
26
Summary of Outcomes From the RECORD Trials

• RECORD 1 and 2 trials (THR)
• There was reduced risk of the primary efficacy
  outcome with prolonged rivaroxaban (started 68
  hours postoperatively, for 35 4 days) when
  compared with enoxaparin given as either
  prolonged (started evening before surgery, for 36
  4 days) or standard-duration (started evening
  before surgery, for 13 2 days) prophylaxis.
• RECORD 1 The primary efficacy outcome occurred
  in 1.1 percent of patients given rivaroxaban and
  3.7 percent of patients given enoxaparin (ARR
  2.6 95 CI, 1.5 to 3.7 P lt 0.001).
• RECORD 2 The primary efficacy outcome occurred
  in 2.0 percent of patients given rivaroxaban and
  9.3 percent of patients given enoxaparin (ARR
  7.3 95 CI, 5.2 to 9.4 P lt 0.0001).
• RECORD 3 and 4 trials (TKR)
• Rivaroxaban decreased the risk of the primary
  efficacy outcome when compared with enoxaparin.
• RECORD 3 The primary efficacy outcome occurred
  in 9.6 percent of patients given rivaroxaban and
  18.9 percent of patients given enoxaparin (ARR
  9.2 95 CI, 5.9 to 12.4 P lt 0.001).
• RECORD 4 The primary efficacy outcome occurred
  in 6.9 percent of patients given rivaroxaban and
  in 10.1 percent of patients given enoxaparin (ARR
  3.19, 95 CI, 0.71 to 5.67 P 0.0118).
• In all four trials, there were no significant
  differences in the risk for the primary safety
  outcome of major bleeding or for the risks of
  mortality or minor bleeding outcomes.

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
27
Summary of Conclusions

• Estimated native (i.e., without pharmacological
  prophylaxis) incidence of DVT after THR and TKR
  surgery was 39 percent and 46 percent,
  respectively.
• Pharmacological prophylaxis decreases the risk of
  DVT with some increased risk of minor bleeding
  when compared with no pharmacological
  prophylaxis.
• LMWH may decrease the risk for DVT when compared
  with warfarin at the expense of increases in
  major and minor bleeding.
• LMWH provides greater protection against DVT and
  PE when compared with unfractionated heparin
  while reducing the risk of bleeding and
  heparin-induced thrombocytopenia.
• LMWH was not as effective in protecting against
  the risk of DVT when compared with an injectable
  factor Xa inhibitor, although the odds of
  bleeding were reduced.
• Prolonged prophylaxis decreased the risk of
  thromboembolism at the risk of increased minor
  bleeding when compared with standard-duration
  prophylaxis.

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
28
Gaps in Knowledge

• Inadequate data did not permit conclusions about
  the comparative benefits and adverse effects
  associated with VTE prophylaxis in
  nonjointreplacement surgery.
• More information is needed on the following
  aspects of VTE prophylaxis in the setting of
  major orthopedic surgery
• Clinically important outcomes including
  symptomatic venous thromboembolism,
  post-thrombotic syndrome, clinically relevant
  bleeding, prosthetic infection, reoperation, and
  mortality and whether intermediate outcomes
  predict health outcomes
• Surgical, postsurgical, or patient factors that
  predict outcomes
• The optimal followup period needed to determine
  longer term outcomes
• Optimal duration of thromboprophylaxis
• The role of combined pharmacological and
  mechanical prophylaxis

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
29
What To Discuss With Your Patients

• General background information on the risk of
  thromboembolic disease
• That thromboembolic disease is a major risk after
  jointreplacement surgery and why some form of
  prophylactic treatment is indicated
• Options for prophylaxis
• Bleeding as the major risk of pharmacological
  prophylaxis

Sobieraj DM, Coleman CI, Tongbram V, et al.
Comparative Effectiveness Review No. 49.
Available at www.effectivehealthcare.ahrq.gov/thro
mbo.cfm.
30
Resource for Patients

• Preventing Blood Clots After Hip or Knee
  Replacement Surgery or Surgery for a Broken Hip,
  A Review of the Research for Adults is a free
  resource for patients. It can help patients talk
  with their health care professionals about the
  many options for treatment. It provides
  information about
• Pharmacological options for preventing venous
  thromboembolism (VTE)
• Nonpharmacological options for preventing VTE
• Current evidence of effectiveness and harms
  associated with VTE-prevention methods
• Questions for patients to ask their doctor