Cardiovascular Complications After Joint Replacement Surgery:

A Crossroad in Anticoagulation

Vincent D. Pellegrini Jr, MDProfessor and Chair

Department of Orthopedic Surgery Medical University of South Carolina

Charleston, South Carolina

Moderator:Samuel Z. Goldhaber, MD

Professor of MedicineHarvard Medical School

DirectorVenous Thromboembolism Research Group

Staff CardiologistBrigham and Women's Hospital

Boston, Massachusetts

Panelists:Kevin J. Bozic, MD, MBA

William R. Murray ProfessorVice Chair

Department of Orthopaedic Surgery University of California, San Francisco

..

Timing of MI Following THR/TKR Surgery: A Nationwide Cohort Study

Cumulative incidence rates of AMI:A: Patients undergoing THR B: Patients undergoing TKR

66,524 patients with THR, 28,703 patients with TKR, and 286,165 matched controls 99.1% had received thromboprophylaxis; 93%, LMWH. Study done in Denmark.

Risk of AMI is substantially increased in the first 2 weeks after THR (25-fold) and TKR (31-fold) surgery compared with controls.

Lalmohamed A, et al.[1]

IMAGES NO LONGER AVAILABLE

ASA Physical Status Classification System

American Society of Anesthesiologists.[2]

ASA Physical Status

Description

1 A normal healthy patient

2 A patient with mild systemic disease

3 A patient with severe systemic disease

4 A patient with severe systemic disease that is a constant threat to life

5 A moribund patient who is not expected to survive without the operation

6 A patient declared brain-dead whose organs are being removed for donor purposes

Minimizing CV Risk

• Principal advancement in joint replacement surgery has

been improvement in anesthetic techniques, especially

the use of regional anesthesia

• Stratify perioperative risk and ensure all modifiable risk

factors have been optimized

VTE Prevalence After Major Orthopaedic Surgery Without Prophylaxis

Procedure DVT(Total, %)

PE(Total, %)

Fatal PE(%)

Total hip replacement

42-57 0.9-28 0.1-2.0

Total knee replacement

41-85 1.5-10 0.1-1.7

Geerts, WH, et al.[3]

…

Types of VTE Prophylaxis: 2008 Survey

Anderson FA, et al.[5]

Rivaroxaban (FDA-approved)

•RECORD1: Rivaroxaban 10 mg vs enoxaparin 40 mg for 5 weeks, THRa

•RECORD2: Rivaroxaban 10 mg for 5 weeks vs enoxaparin 40 mg for 10-14 days, THRb

•RECORD3: Rivaroxaban 10 mg vs enoxaparin 40 mg for 13-17 days, TKRc

•RECORD4: Rivaroxaban 10 mg vs enoxaparin 30 mg every 12 hours for 17 days, TKRd

a. Eriksson BI, et al.[6]

b. Kakkar AK, et al.[7] c. Lassen MR, et al.[8] d. Turpie AG, et al.[9]

Novel Oral Anticoagulants: Trials in Major Orthopaedic Surgery

Apixaban: Pooled Results of ADVANCE-2 and ADVANCE-3N = 8464 patients undergoing TKR (ADVANCE-2) and THR (ADVANCE-3)Not FDA approved for use in major orthopaedic surgery

Raskob GE, et al.[10]

Apixaban Enoxaparin

Risk Difference(95% CI)

P Value

Efficacy

Major VTE, % 0.7 1.5 -0.8(-1.2 to -0.3) .001

Safety

Major bleeding, % 0.7 0.8 -0.02(-0.4 to 0.4) --

Clinically relevant nonmajor bleeding, % 3.6 4.2 -0.6

(-1.4 to 0.3) --

Dabigatran: RE-MOBILIZE, RE-MODEL, RE-NOVATE: Pooled AnalysisNot FDA approved for use in major orthopaedic surgery

EnoxaparinDabigatran

150 mg Dabigatran

220 mg

EfficacyP Value P Value

Major VTE and VTE-related Mortality, %

3.3 3.8 .91 3.0 .20

Safety

Major bleeding, % 1.4 1.1 0.16 1.4 .61

Major + clinically relevant nonmajor bleeding 5.0 5.6 .58 5.6 .56

Friedman RJ, et al.[11]

N = 12,729 RivaroxabanEnoxapari

n

Hazard Ratio

(95% CI)P

Value

Efficacy

Composite of symptomatic VTE + all-cause mortality, % 0.5 1 0.48

(0.30-0.76) .001

Safety: Bleeding Events

Major bleeding, % 0.3 0.2 1.62(0.77-1.53) .23

Major + clinically relevant nonmajor bleeding, % 2.8 2.5 1.17

(0.93-1.46) .19

Turpie AGG, et al.[12]

RECORD 1-4: Pooled Analysis

Rivaroxaban Enoxaparin

Hazard Ratio

(95% CI) P Value

Bleeding Events*

Major bleeding 0.3% 0.2% 1.62(0.77-1.53)

.23

Major + non-major clinically relevant bleeding 2.8% 2.5% 1.17

(0.93-1.46).19

Any bleeding 6.6% 6.2% 1.07(0.92-1.24)

.38

Turpie AG, et al.[12]

*Day 12 ± 2 active treatment pool.

RECORD 1-4: Pooled Analysis - Safety

Enoxaparin

Rivaroxaban

RECORD Study Design

Mandatorybilateralvenography

R

SURGERY

FOLLOWUP

Evening before surgery

Day 1

Double blind

Last dose, daybefore venography

6-8 hours postsurgery

Turpie AGG, et al.[12]

Summary

• Patients undergoing major orthopaedic surgery are at

high risk for developing VTE/PE.

• Effective prophylaxis reduces this risk considerably.

• As new agents become more widely used, the use of

the older oral anticoagulants, including LMWH and

warfarin, is declining.

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