Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

Title: Prevention of venous thromboembolism (VTE) in orthopedic surgery.

Set of related questions for consideration

PICO-Question #1: In patients undergoing major orthopedic surgery (total hip and knee replacement, hip fracture surgery), what is the relative impact of thromboprophylaxis (any agent, any external mechanical intervention) compared to no thromboprophylaxis on VTE (ie, asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; and total mortality?

PICO-Question #2: In patients undergoing major orthopedic surgery (total hip and knee replacement, hip fracture surgery), what is the relative impact of aspirin compared to injectable antithrombotic agents (low molecular weight heparins (LMWH) vs. unfractionated heparin vs. fondaparinux) compared to oral vitamin K antagonists (VKAs) compared to external mechanical interventions on VTE (ie, asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; and total mortality?

PICO-Question #3: In patients undergoing major orthopedic surgery (total hip and knee replacement, hip fracture surgery) who have known contraindications to antithrombotic agents, what is the relative impact of prophylactic vena cava filter placement compared to any external mechanical intervention on VTE (ie, asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; placement risks and long-term risks associated with vena cava filters; and total mortality?

PICO-Question #4: In patients undergoing major orthopedic surgery (total hip and knee replacement, hip fracture surgery), what is the relative impact of pre-discharge ultrasound DVT screening (plus DVT treatment, if positive) compared to no pre-discharge DVT screening on VTE (ie, asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; and total mortality?

Elaboration on population for PICO question 1-4:

• What is the overall baseline risk of VTE outcomes in patients undergoing hip surgery, hip fracture surgery, and knee replacement surgery? Does this risk vary over time?
• What is the overall baseline risk of bleeding outcomes in patients undergoing hip surgery, hip fracture surgery, and knee replacement surgery? Does this risk vary over time?
• What patient characteristics, if any, can differentiate patients according to risk of VTE outcomes in patients undergoing hip surgery, hip fracture surgery, and knee replacement surgery? Do these factors vary across the three surgeries?
• What patient characteristics, if any, can differentiate patients according to risk of bleeding outcomes in patients undergoing hip surgery, hip fracture surgery, and knee replacement surgery? Do these factors vary across the three surgeries?

Elaboration on interventions for PCIO question 1-4:

• What are the desirable and undesirable effect estimates when comparing within different class agents (eg, injectable antithrombotic agents: low molecular weight heparins (LMWH) vs. unfractionated heparin vs. fondaparinux)?
• What are the desirable and undesirable effect estimates of combination antithrombotic treatment vs. single modality/agent (eg, mechanical intervention plus ASA)?
• What are the desirable and undesirable effects of different timings of starting thromboprophylaxis (eg, 10 hours or 2 hours before surgery or at different time points post op)?
• What are the desirable and undesirable effects of prolonging thromboprophylaxis (any method) for 30 days or longer compared to no thromboprophylaxis after 7 days?

Elaboration on outcomes for PCIO question 1-4:

• In the absence of patient important outcomes, can the relative risk for such outcomes (eg, less symptomatic VTE) reliably be estimated by measuring surrogate outcomes, such as proximal or distal deep vein thrombosis (DVT) as detected by venography or ultrasound diagnosis?

PICO-Question #5: In patients with other orthopedic conditions (eg, distal to knee injuries; conditions requiring knee arthroscopy; elective spine surgery), what is the relative impact of thromboprophylaxis (any agent, any mechanical intervention) compared to no thromboprophylaxis intervention on VTE (ie, asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; and total mortality?

PICO-Question #6: In patients with other orthopedic conditions (eg, distal to knee injuries; conditions requiring knee arthroscopy; elective spine surgery), what is the relative impact of injectable antithrombotic agents (LMWH vs. unfractionated heparin vs. fondaparinux) compared to mechanical interventions on VTE (ie asymptomatic DVT [surrogate for symptomatic VTE]; symptomatic DVT; non-fatal pulmonary embolism; fatal pulmonary embolism); bleeding (operative site vs. non-operative site); discomfort; re-admission; re-operation; and total mortality?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

Yes. Please see: PICO question #2, #3 and #6 and sub-questions regarding interventions.

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

All patients having specific orthopedic surgeries as mentioned above. Also, see above: Sub-questions regarding population.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

See above: Sub-questions regarding population.

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Prevention of symptomatic venous thromboembolism, death. See also: PICO questions above.

Describe any health-related risks, side effects, or harms that you are concerned about.

Operative site bleeding; non-operative site bleeding; discomfort; re-admission; re-operation; death from bleeding complications; other treatment risks as mentioned in the PICOs above.

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Arthritis and nontraumatic joint disorders
• Cardiovascular disease, including stroke and hypertension
• Pulmonary disease/asthma

AHRQ Priority Populations

• Elderly

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

Among > 7 million patients discharged from American acute care hospitals, postoperative VTE is the second most common medical complication, the second most common cause of excess length of stay, and the third most common cause of excess mortality and excess charges.

Orthopedic surgical procedures carry a particularly high risk of VTE (eg, untreated, 40-60% of patients with hip or knee arthroplasty will develop DVT).

Quality improvement programs, such as the national “Surgical Care Improvement Project” (SCIP) partnership are relying on evidence based clinical practice guidelines to define best practices. Although the ACCP antithrombotic guidelines have been widely used for such purposes, the American Academy of Orthopedic Surgeons (AAOS) published in May of 2007 a new guideline for the “Prevention of Pulmonary Embolism in Patients Undergoing Total Hip or Knee Arthroplasty”. The AAOS guideline recommendations differ substantially from those of the ACCP which has led to a recent comparative analysis of both guidelines(1). The presence of two guidelines that differ in recommendations for the target conditions has the potential to cause major confusion as guideline consumers, such as physicians, patients and policy makers lack clear guidance. The ACCP has invited the AAOS to participate in the development of guidelines based on the review of the orthopedic evidence. AAOS has accepted and appointed a member to our panel.

Furthermore, the Centers for Medicare and Medicaid Services (CMS) will no longer pay for up-charges due to VTE associated with total hip or knee arthroplasties because these were deemed to be “reasonably preventable” if evidence-based guidelines are employed. Hospitals sense a greater urgency and stress the importance of a well-respected and non-biased evidence review to be conducted on this high-impact topic.

Reference: (1) Eikelboom JW, Karthikeyan G, Fagel N, Hirsh J. American association of orthopedic surgeons and American college of chest physicians guidelines for venous thromboembolism prevention in hip and knee arthroplasty differ: what are the implications for clinicians and patients? Chest. 2009 Feb;135(2):513-20.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

The immediate motivation is that the ACCP is preparing to develop the Antithrombotic and Thrombolytic Therapy: ACCP Evidence-Based Clinical Practice Guidelines (9th Edition). However, the underlying motivation is the controversy and resulting variation in the practice of VTE prevention in orthopedic patients.

An evidence review performed by an AHRQ-designated evidence-based practice center would have high credibility and objectivity.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

Yes. Although both the ACCP and AAOS guidelines agree on the goal of preventing symptomatic VTE, such as pulmonary embolism and death, there appears to be uncertainty

• How to select the best available evidence (in terms of study design, outcome measured etc.)
• How to interpret the available evidence (use of surrogate endpoints, such as DVT, and to what extent the surrogate endpoint is associated with patient important outcomes)
• Whether recommendations are formulated for typical patients or should be presented to include special populations with different baseline risks (for VTE or treatment associated undesirable events, such as bleeding)
• Whether, depending on the intervention used, the balance of desirable outcomes (reduction in symptomatic VTE, mortality) clearly outweigh the undesirable events (such as of operative site bleeding, risk for re-hospitalization and re-operation, and bleed related mortality). In a letter to the AAOS, the ACCP has voiced their concern that patients undergoing elective hip or knee surgery could either receive no prophylaxis or aspirin alone should practitioners apply the AAOS guideline. This situation presents a potential for harms from inaction if those differences are not adequately addressed in a timely manner.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

A systematic review addressing these questions will correct weaknesses in the evidence selection and interpretation and facilitate improved guideline development from stakeholder organizations. Utilizing a systematic review from an independent organization, such as the AHRQ, would facilitate development of a jointly developed guideline by the ACCP and the AAOS. In addition, other organizations, such as performance measure developers and endorsers, would be able to better define best care practices without the need to resort to conflicting guidelines.

Describe the timeframe in which an answer to your question is needed.

No later than August 2010.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Increasingly, the elderly population is undergoing arthroplasty procedure of the lower extremity. However, large variation exists of adherence to antithrombotic guidelines (2,3). Since age itself is identified as an independent risk factor for thromboembolism and multiple risk factors are frequently present, this population group is at particular risk for VTE. In addition, a recent observational study, among surgical patients who developed DVT, some form of prophylaxis had been used in only 44% of patients; but once diagnosed with DVT, surgical patients receive permanent IVC filters more often than medical patients (20% vs. 14%)(4). The long term risks of IVC filters are, however, less well understood.

References: (2) Yu HT, Dylan ML, Lin J, Dubois RW. Hospitals' compliance with prophylaxis guidelines for venous thromboembolism. Am J Health Syst Pharm. 2007 Jan 1;64(1):69-76.

(3) Tapson VF, Hyers TM, Waldo AL, Ballard DJ, Becker RC, Caprini JA, Khetan R, Wittkowsky AK, Colgan KJ, Shillington AC; NABOR (National Anticoagulation Benchmark and Outcomes Report) Steering Committee. Antithrombotic therapy practices in US hospitals in an era of practice guidelines. Arch Intern Med. 2005 Jul 11;165(13):1458-64.

(4) Seddighzadeh A, Zurawska U, Shetty R, Goldhaber SZ. Venous thromboembolism in patients undergoing surgery: low rates of prophylaxis and high rates of filter insertion. Thromb Haemost. 2007 Dec;98(6):1220-5.

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A systematic review addressing these questions will correct weaknesses in the evidence selection and interpretation and facilitate improved guideline development from stakeholder organizations. Utilizing a systematic review from an independent organization, such as the AHRQ, would facilitate development of a jointly developed guideline by the ACCP and the AAOS. In addition, other organizations, such as performance measure developers and endorsers, would be able to better define best care practices without the need to resort to conflicting guidelines.

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