Peri-Operative Management of Patients with Proximal Femoral Fractures on Clopidogrel

Current Practice in UK Orthopaedic Departments

Inman D, Michla Y, Partington P

Kreibich Memorial Research Prize March 2007

Proximal Femoral Fractures

Common in the elderly Most common fractures alongside vertebrae

& distal radius Around 57,500 cases / year Numbers rising 59% of patients have comorbidities Overall mortality 33% in 1st year post-op

Balasegaram et al. Trends in Hospital Admissions from Fractures of the Hip & Femur in England. J. Public Health Med. 2001 Mar; 23(1): 11-17

J J W Roche, R T Wenn, O Sahota, C G Moran. Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ  2005;331:1374

Clopidogrel Bisulphate ( PlavixR )

Thebault JJ, Kieffer G, Lowe WS, Cariou R. Repeated dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Haemost 1999;25(Suppl 2):9 –14Leeksma C, Cohen J. Determination of the Lifespan of Human Blood Platelets using Labelled Diisoprpylfluorophosphonate. J Clin Invest 1956; 35(9): 964-9Billett et al. Antiplatelet & Arterial Thrombosis. Clin Ger Med 2006; 22: 57 – 74Weber et al. Recovery of Platelet Function after Discontinuation of Clopidogrel Treatment in Healthy Volunteers. Br J Clin Pharmacol 2001; 52: 333-6

• Potent platelet inhibitor

• Irreversibly inhibits ADP receptors on platelet membrane Causes a twofold increase in bleeding time Acts within 4-6 hours Active metabolite excreted in less than 24 hours

• Effects last for life of platelet (8-9 days)

• Normal platelet function noted 7 days after withdrawal

Clopidogrel Licence

Prevention of occlusive vascular events– Intolerance of aspirin– CVA– Non-ST segment elevation Acute Coronary Syndrome– Peripheral Vascular Disease

Post coronary stent insertion– Decreases risk of subacute stent occlusion– Prescribed for up to 1 year following insertion

(Bare Metal Stents vs Drug Eluting Stents)

NICE Press Release, July 2004 & NICE Guidelines, May 2005CAPRIE Steering committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-39.CURE Trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New England Journal of Medicine 2001; 345: 494-503.

Dawkins KD, Gershlick T, de Belder M et al. Percutaneous coronary intervention: recommendations for good practice and training. Heart2005;91;1-27

The Dilemma…

Increasing % of surgical patients on Clopidogrel

Elective surgery guidelines– cease Clopidogrel for 7-10 days pre-operatively to allow

return of normal platelet function

Patients with proximal femoral fractures– Elderly population bedridden and in pain– Mortality increases as delay to surgery increases– Delay of ≥ 4 days significantly increases mortality

Weller et al. The Effect of Hospital Type & Surgical Delay on Mortality after Sugery for Hip Fracture. J Bone Joint Surg (Br) 2005; 87-B: 361-6Moran et al. Early Mortality After Hip Fracture: Is Delay Before Surgery Important? J Bone Joint Surg (Am) 2005; 87-A(3): 483-9

Aims of Study

1. To establish current practice amongst Orthopaedic surgeons in the UK

2. To establish if practice of peri-operative withdrawal of Clopidogrel is evidence-based or anecdotal

3. To design an interim protocol for these patients pending further research

Materials and Methods

Postal questionnaire

Sent to each Orthopaedics & Trauma department in Great Britain

Questionnaire Does department have written protocol for trauma patients who are

taking Clopidogrel alone or Clopidogrel and Aspirin?

Do you;

Continue Clopidogrel and operate as soon as medically fit Stop Clopidogrel and operate as soon as medically fit Stop Clopidogrel and wait 10 days before surgery Other

Asked to indicate evidence for management

Free comments

Results (1)

244 questionnaires sent

139 orthopaedic departments responded (57% response rate)

15% of centres that responded have written guidelines

Results (2)

Continue clopidogrel andoperate when medically fit 19%

(26)Stop clopidogrel and operateas soon as medically fit 41%

(56)

Stop clopidogrel and wait 10 days 10%

(14)

Other 30% (41)

0 10 20 30 40 50

Other Policies (30%)

15 centres stop and wait 5-10 days 1 centre stops and waits 14 days

Local anaesthetic department requirement

2 centres had not heard of clopidogrel 10 centres took advice from the anaesthetic

department regarding timing of surgery 6 centres took advice from the

haematologists

Evidence Quoted

3 centres (2%) quoted published literature – 2 of these quoted the BNF

(Only gives advice for elective surgery)

7 centres (5%) reported anecdotal increased bleeding perioperatively if patient on clopidogrel

Clopidogrel and Emergency Surgery

No published orthopaedic data Increased peri-procedure blood loss reported

in cardiothoracic literature Intra-operative aprotinin therapy effective in

patients treated with clopidogrel <5 days before CABG surgery

Leong JY et al. Clopidogrel and bleeding after coronary artery bypass graft surgery. Ann Thorac Surg. 2005 Sep; 80(3): 928-33.Van der Linden J, Lindvall G, Sartipy U. Aprotinin Decreases Postoperative Bleeding and Number of Transfusions in Patients on Clopidogrel Undergoing CoronaryArtery Bypass Graft Surgery: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial Circulation 2005;112;276-280

Blood Transfusion and the AnaesthetistGuidelines published by

The Association of Anaesthetists of Great Britain and IrelandDec 2005

…Clopidogrel is a pro-drug. The active metabolite circulates for approximately 18 hours after the most recent dose and permanently inhibits any platelets present during this time (whether endogenous or transfused). Platelet therapy during this time is unlikely to be helpful. If possible, emergency surgery is best delayed for at least 24 hours after the last dose of clopidogrel…

…The combination of platelet transfusions and aprotinin therapy has been used to decrease blood loss.

Conclusions

• Wide variation in practice

• Current practice based on anecdote

• Establish indication for Clopidogrel

• Further research required comparing outcome of early versus delayed surgery

Patient with #NOF on Clopidogrel

<1 year post coronary stent<1 year post coronary stentinsertioninsertion

Other indicationOther indication

Discuss with interventional cardiologist re. safety of stopping

ClopidogrelConsider continuing throughout

perioperative period

Stop Clopidogrel on admission

Work up for theatre as normal

Operate >24 hours following last doseAvoid spinal anaesthesia

Meticulous haemostasisPlatelet transfusion/ aprotinin available

Restart Clopidogrel on 2nd post-op day/ when local haemostasis acheived

Thank you(Prevention is better than cure)