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DVT Prophylaxis in Orthopedic Patients Rogers Kyle 11/27/12

DVT Prophylaxis in Orthopedic Patients

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DVT Prophylaxis in Orthopedic Patients. Rogers Kyle 11/27/12. Key Messages. The new ACCP guidelines for prevention of VTE in orthopedic surgery patients were published in 2012 and contain many new options - PowerPoint PPT Presentation

Text of DVT Prophylaxis in Orthopedic Patients

DVT Prohylaxis in Orthopedic Patients

DVT Prophylaxis in Orthopedic PatientsRogers Kyle11/27/12Key MessagesThe new ACCP guidelines for prevention of VTE in orthopedic surgery patients were published in 2012 and contain many new optionsASA is now included as one of the acceptable pharmacologic agents for initial prophylaxis (1B) as are SCDs (1C)LMWH is still the preferred alternative (2C/2B)SCDs should be used in combination with all pharmacologic therapies (2C)Prophylaxis should be extended to 35 days (2B)With increased bleeding risk used SCDs or no prophylaxis (2C)If patient refuses injection use apixaban or dabigatran

Key Messages

Key Messages

Key Messages

ACCP 9 (2012)Symptomatic DVT/PE vs. increased major bleedingthe trade-offPatient Values and PreferencesHistorical PointsTrials before 2000 used asymptomatic DVT on screening as primary end point.No general agreement on bleedingmajor and minor in older studiesclinically relevant non-major in recent studies NOT included in current update

Major BleedingDefinitionsany fatal bleedingbleeding into a critical organ (eg, retroperitoneal, intracranial, intraocular, or intraspinal)clinically overt (eg, GI) bleeding associated with a 2 g/dL drop in hemoglobin level or requiring 2 units of blood transfusedbleeding leading to reoperationBleeding Risk

Baseline Risk of DVT/PEChanges over timeLOS for HFS in 60s 35 days. Now 3.2 days.Pre-1980 15 to 30% without prophylaxisMany changes in the interimSurgical techniqueEarly ambulationEarlier dischargePost prophylaxis dropped to 1-2% by 2001

Baseline Risk of DVT/PEA Randomized Controlled Trial of a Low-Molecular-Weight Heparin (Enoxaparin) to Prevent Deep-Vein Thrombosis in Patients Undergoing Elective Hip Surgery (NEJM 1986)LMWH vs. placebo100 pts., elective THAVenography (impedance pleth/fibrinogen) in 7610.8% in LMWH vs. 51.3% in placeboasymptomatic

Baseline Risk of DVT/PESince 2003 rate of symptomatic DVT/PE on LMWH prophylaxis is 1.15% (0.8% DVT, 0.35% for PE)Symptomatic VTE rate off prophylaxis 1.8% DVT, 1% PE.Assume that the risk reduction for DVT and PE on LMWH for symptomatic and asymptomatic50-60% DVT, 2/3s PECumulative 7, 14, 35 daysIncludes TKA, THA, HFS

Baseline Risk of DVT/PE

Baseline Risk of DVT/PE

Baseline Risk of Bleedingdifficult to estimateBetter op techniquesMostly from placebo (or GCS) arm of LMWH trials and the PEP trial

PEP TrialPrevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial (Lancet 2000)Not in US17,000+ pts THA or HFS160 mg ASA + any other thromboprophylaxis thought necessary vs. placeboreductions in pulmonary embolism of 43% (95% CI 1860; p=0002) and in symptomatic deep-vein thrombosis of 29% (348; p=003) - including patients receiving subcutaneous heparin

Baseline Risk of Bleedingdifficult to estimateBetter op techniquesMostly from placebo (or GCS) arm of LMWH trials and the PEP trialMedian rate 1.5%Can we estimate the bleeding risk pre-op?

Baseline Risk of Bleedingdifficult to estimateBetter op techniquesMostly from placebo (or GCS) arm of LMWH trials and the PEP trialMedian rate 1.5%Can we estimate the bleeding risk pre-op?did not find any bleeding risk assessments that have been sufficiently validated in the orthopedic surgery population

RecommendationsTHA, TKA, HFS10-14 days Low molecular weight heparin (LMWH) FondaparinuxApixabanDabigatranRivaroxabanLow dose heparin (LDUH)Adjusted dose coumadinASA (One panel member believed strongly that aspirin alone should not be included as an option)Intermittent pneumatic compression devices (IPCD)LovenoxTHA30 mg SQ Q12H starting 12-24 hrs post-op OR40 mg SQ QD starting 12 3 hrs post-op7-14 days; up to 35 days (40 mg QD)TKA30 mg SQ BID7-14 days

LovenoxBenefit13 fewer VTE/1000 with 7-14 daysNo increased major bleedingSymptomatic DVT reduced by with extended treatment (9 fewer VTE/1000)No mortality benefit

FondaparinuxFondaparinux vs. enoxaparin; THA (Lancet 2002)10 days 2.5 mg fondaparinux vs. 30 mg BID enoxaparinNon-inferiorFondaparinux 6-8 days followed by placebo vs. fondaparinux for total 19-23 days; HFS (Arch Int Med 2003)12 fewer VTE/100012 more major bleeds/1000CoumadinFew trials (8 RCTs/700 pts); few events55% reduction DVT; 80% reduction PEINR 2-3Begin post-op day of surgery18 fewer VTE/10007 more major bleeds/1000

Low Dose Unfractionated Heparin5,000 Units SQ BID vs. TIDChest 2011 no difference in medical pts (vs. Chest 2007)AHRQ Guidelines Not recommended13 fewer VTE/10004 more major bleeds/1000ASAPulmonary Embolism Prevention (PEP) trial160 mg, 35 daysHFS (13,000+ pts), THA (4,000+ pts)7 fewer VTE/10003 more major bleeds/10002 more non-fatal MIs

Intermittent Pneumatic Compression Devices (IPCD)Not GCS (CLOTS trial Lancet 2009)Number of IPCD studies , one venous foot pump study (TKA; 60 pts, less extensive clot; 1992)16 fewer VTE/1000Compliance is problematic; newer battery powered might be betterApixabanApproved in Europe, CanadaADVANCE 1, 2, and 3 trialsADVANCE 1 (NEJM 2009)TKA2.5 mg BID apixaban vs. 30 mg BID enoxaparin x 10-14 daysSymptomatic and asymptomatic DVT, PE, death Total venous thromboembolism and all-cause mortalityNo difference but did not meet prespecified criteria for non-inferiority; less clinically relevant bleeding but not majorApixabanADVANCE 2 (Lancet 2010)TKA2.5 mg BID apixaban vs. 40 mg QD enoxaparin x 10-14 daysAlso a non-inferiority trial but demonstrated superiority in preventing DVT (mostly asymptomatic); not PE, mortalitySame bleeding?? difference in enoxaparin (30 mg BID vs. 40 md QD)

ApixabanADVANCE 3 (NEJM 2010)THAApixaban 2.5 mg BID vs. enoxaparin 40 mg QD x 35 daysAlso a non-inferiority trial but demonstrated superiority in preventing DVT (mostly asymptomatic); not PE, mortalitySame bleeding

DabigatranIn Europe and CanadaRENOVATE (Lancet 2007)THADabigatran 220 mg or 150 mg QD vs. enoxaparin 40 mg QD30 daysTotal venous thromboembolism and all-cause mortalityNon-inferior

DabigatranRE-NOVATE II (Thrombosis Haemostasis 2010)THADabigatran 220 mg QD vs. enoxaparin 40 mg QD28-35 daysPrimary endpoint - DVT (sym and asym)/PE, mortality Total venous thromboembolism and all-cause mortalityNon-inferiorityNon-inferior for primary endpoint (mostly asym)Superior for major VTE/VTE related death but only because of asym proximal DVT

RivaroxabanFDA approved for DVT prophylaxis in THA, TKARECORD 1 (NEJM 2008), and 2 (THA); 3 and 4 (TKA)10 mg rivaroxaban QD vs 40 mg enoxaparin QD extended prophylaxis - 35 daysTHAPrimary endpoint - any DVT, nonfatal pulmonary embolism, or death from any cause.Non-inferiority/superiorityRivaroxaban superior efficacy; similar bleeding risk



LMWH vs. LDUHACCP9 20% relative risk reduction of primarily asymptomatic DVT in favor of LMWH (RR, 0.80; 95% CI, 0.73-0.88), with similar effects seen in the subgroups of THA, TKA, and HFSLMWH may reduce symptomatic VTE from 16 per 1,000 with LDUH to 13 per 1,000 without an increase in major bleedingQ8H vs Q12H LDUH?LMWH vs. Coumadin initial vs. extended prophylaxisACCP9Initial - LMWH less asymptomatic DVT, no diff PE; increased bleeding (initial prophylaxis)Extended Coumadin less PE, same DVT, more more bleedsLMWH vs. ASA - initial vs. extended prophylaxisACCP 92 small trials (one is an abstract). One trial was SCDs + LMWH vs. SCDs + ASAInitial and extended ASA more asymptomatic DVT, few PEs, no bleeding differenceevidence from a head-to head comparison of LMWH compared with aspirin is sparse and of low quality

LMWH vs. Fondaparinux - initial vs. extended prophylaxisACCP 9pooled results failed to demonstrate or exclude a beneficial or detrimental effect of fondaparinux on symptomatic DVT and PE despite a substantial reduction in asymptomatic DVTmay increase major bleeding events by nine per 1,000 (fondaparinux)LMWH vs. Rivaroxaban - initial vs. extended prophylaxisACCP 9Rivaroxaban reduced symptomatic DVT by > 50%There may be more bleedsTherefore LMWH more appealing than rivaroxaban for initial prophylaxis; extended unknownLMWH vs. Dabigatran - initial vs. extended prophylaxisACCP 9Dabigatran similar to enoxaparin (note many of the studies used a 150 mg dose of dabigatran)

LMWH vs Apixaban - initial vs. extended prophylaxis ACCP 9Apixaban reduced symptomatic DVT 60% vs. LMWH (very small numbers)No major differences in bleedingStill favor LMWH (longer experience)IPCD + ASA vs LMWHACCP 9There are 2 articles that are interesting and make the choice of prophylaxis in THA/TKA difficultThese articles are both reviewed in ACCP 9. They are considered low-quality evidence with significant methodologic limitationsHowever, these studies either demonstrated a similar or reduced rate of DVT/PE along with a reduced risk of bleeding (remember definition of bleeding)IPCD + ASA vs LMWHDeep Vein Thrombosis Prevention in Joint Arthroplasties (Journal of Arthroplasty 2006)136 patients (no fractures)SCDs (mobile) + 100 mg ASA vs. enoxaparin 40 mgVenograms 5-8 days and clinical evaluation at 30 daysPrimary DVT; secondary bleedingResultsDVT 28.3% LMWH, 6.6% SCDs/ASA; more prox DVT and contralateral DVT in LMWHVery few bleeds in either group (no difference)Cost - $2600+/pt less with SCD/ASA Total savings/1000 pts - $2,628,557

IPCD + ASA vs LMWHThrombosis Prevention After Total Hip Arthroplasty (J Bone Joint Surg 2010)400+ ptsSCDs (mobile) +/- ASA 81 mg vs enoxaparin 30 mg BID 40 mg QD at dischargeU/SPrimary bleeding; secondary DVT/PEResults Less bleeding (esp major) 0% vs 6%No difference in DVT/PE

SummaryTKA, THA, HFSLMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH, adjusted-dose VKA, aspirin or an IPCD - all are recommended vs no prophylaxisLMWH recommended over all alternativesLMWH 12 hr before or after surgery (not 4 hrs post op)Extended duration up to 35 days recommendedDual prophylaxis recommended IPCD + antithrombotic agent

SummaryIf not LMWH (HIT)Apixaban, dabigatran, rivaroxaban, VKA, fondaparinux, IPCD, IPCD + ASAMore bleeding with fondaparinux, rivaroxaban, VKACompliance mechanicals, VKA, injection as outptApixaban 2.5 mg BID, Dabigatran 220 mg QD

SummaryIncreased bleeding riskTKA, THA, HFS IPCD or no prophylaxisRemember that ACCP 9 defines bleeding risk as major. Surgeons do not.SummaryIncreased bleeding riskTKA, THA, HFS IPCD or no prophylaxisIf the risk factor is an antiplatelet agent consider pharmacologic prophylaxisDont use IVC filter as primary preventionDont use IVC filter even if increased bleeding risk/contraindication to pharmacologic and mechanical prophylaxis