3.5 Cessation of medications that affect haemostasis

3.5.2 Noncardiac surgery or other invasive procedures

Aspirin therapy

One systematic review132 and one prospective cohort study published since the publication of that review133 compared outcomes among patients whose aspirin therapy was stopped before noncardiac surgery or invasive procedure with patients whose aspirin therapy was continued. The systematic review identified Level II and III studies of aspirin cessation versus aspirin continuation in a number of different surgeries and procedures, including spinal and epidural anaesthesia, oral surgery, biopsy, ophthalmology, orthopaedic surgery, urology and vascular surgery.

Overall, the authors of the systematic review concluded that aspirin should only be ceased before noncardiac surgery or invasive procedures if the bleeding risks associated with its continuation outweigh the cardiovascular risks of its withdrawal.

Clopidogrel therapy

Only one study was identified investigating the cessation of clopidogrel in patients undergoing noncardiac surgery or invasive procedures.134 The study was of poor quality and the results could not be relied on.

NSAID therapy

The evidence base for NSAID therapy comprised one RCT,135 one prospective cohort study,136 and one retrospective cohort study.137 All three studies were in patients undergoing hip arthroplasty. The studies demonstrated that blood loss during and after surgery was greater in patients not ceasing NSAID therapy before surgery, compared with patients either not receiving NSAID therapy or ceasing therapy at least 2 weeks before surgery. NSAID therapy did not affect haemoglobin levels,136,137 but appeared to affect transfusion requirements, with more blood being transfused in patients on NSAID therapy compared with patients who did not receive NSAID therapy.136

Warfarin

The review identified eight studies comparing the discontinuation of warfarin therapy before surgery or procedure with continuing warfarin therapy until surgery or procedure, or receiving bridging therapy until surgery or procedure.133,134,138–143 The evidence base included two systematic reviews,140,144 three RCTs,138,139,141 one prospective cohort study143 and one retrospective cohort study142 that were not included in the published reviews.

One systematic review found that arterial thromboembolism and stroke rates for patients undergoing all types of surgery and invasive procedures were not higher for patients discontinuing warfarin without bridging therapy compared with patients continuing warfarin therapy or receiving heparin bridging therapy.140 The review also found that major bleeding was rare in patients undergoing dental procedures, arthrocentesis, cataract surgery and upper endoscopy or colonoscopy, with or without biopsy. The authors concluded that warfarin therapy does not need to be withheld for patients undergoing these procedures. These findings were supported by the second systematic review,144 and by two RCTs in dental surgery;138,139 all of which found no difference in bleeding between patients ceasing warfarin therapy before the procedure or continuing therapy until surgery. The remaining RCT also found no increase in haematoma formation with continuing warfarin therapy in patients undergoing transfemoral coronary angiography, compared with patients who had their warfarin therapy withheld.141

The analysis by Dunn and Turpie (2003) concluded that for other invasive and surgical procedures, warfarin needs to be withheld.140 The decision on whether to administer perioperative intravenous heparin or subcutaneous low-molecular-weight heparin should be individualised, based on an estimation of the patient’s risks of thromboembolism and bleeding, and reference to relevant guidelines (e.g. those from the American College of Chest Physicians6 and the Australasian Society of Thrombosis and Haemostasis7).

EVIDENCE STATEMENTS – cessation of medications	Evidence	Consistency	Clinical impact	Generalisability	Applicability
In patients undergoing coronary artery bypass surgery, the effect of continuing aspirin monotherapy until the day of surgery on mortality, morbidity (myocardial infarction and pericardial effusion), ICU length of stay, hospital length of stay, perioperative blood loss and transfusion requirement is uncertain.			X
In patients undergoing coronary artery bypass surgery, there may be an increased risk of bleeding, transfusion requirement and reoperation for bleeding if clopidogrel is not ceased at least 5 days before surgery. The impact on morbidity and mortality is uncertain.	X
In patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass who are receiving combination antiplatelet medication, the continuation of clopidogrel until the time of surgery may be associated with an increase in volume of transfusion; however, the available evidence is poor.	X
In patients undergoing off-pump coronary artery bypass graft surgery who are receiving combination antiplatelet therapy, continuing clopidogrel within the 7-day period before surgery may be associated with an increased likelihood of red blood cell transfusion and reoperation for bleeding. The effect on mortality, ICU length of stay or hospital length of stay is uncertain.
In patients undergoing noncardiac surgery or invasive procedures, the effect of continuing aspirin therapy on morbidity, mortality and transfusion is uncertain, given the heterogeneity of the populations studied.
In patients undergoing orthopaedic surgery receiving NSAID therapy, blood loss and transfusion requirements are increased when NSAID therapy is continued until the day of surgery. There was insufficient evidence to determine the effect of the timing of cessation of NSAID therapy.
In patients undergoing noncardiac surgery, the effect of continuing clopidogrel on morbidity, mortality and transfusion is uncertain.	X	NA	X
In patients undergoing minor dental procedures, arthrocentesis, cataract surgery, upper gastrointestinal endoscopy or colonoscopy with or without biopsy, morbidity and mortality are unaffected when warfarin is continued. In patients undergoing more complex procedures, the effect on mortality and morbidity is unclear when warfarin is continued or when bridging therapy is administered.

ICU, intensive care unit; NSAID, nonsteroidal anti-inflammatory drug

(See Table 2.2)

RECOMMENDATIONS – cessation of medication

R7 Grade C	In patients undergoing CABG either with or without CPB (OPCAB), clopidogrel therapy should be stopped, where possible, at least 5 days before surgery (Grade C).
R8 Grade C	In patients undergoing noncardiac surgery, it is reasonable to continue low dose aspirin therapy. This may require specific evaluation in neurosurgery and intraocular surgery (Grade C).
R0 Grade C	In patients undergoing elective orthopaedic surgery, NSAID therapy should be ceased preoperatively to reduce blood loss and transfusion (Grade C). The timing of the cessation should reflect the agent’s pharmacology.
R10 Grade B	In patients undergoing minor dental procedures, arthrocentesis, cataract surgery, upper gastrointestinal endoscopy without biopsy or colonoscopy without biopsy, warfarin may be continued (Grade B).

PRACTICE POINTS – cessation of medication

PP8	In patients undergoing cardiac surgery, aspirin may be continued until the time of surgery.
PP9	In patients receiving clopidogrel who are scheduled for elective noncardiac surgery or other invasive procedures, a multidisciplinary approach should be used to decide whether to cease therapy or defer surgery, balancing the risk of bleeding and thrombotic events. Specific evaluation is required for patients who had a recent stroke, or received a drug-eluting stent within the last 12 months or a bare metal stent within the last 6 weeks. If a decision is made to cease therapy preoperatively, this should occur 7–10 days before surgery.
PP10	In patients receiving warfarin who are scheduled for elective noncardiac surgery or other invasive procedures (excluding minor procedures—see Recommendation 10); specific management according to current guidelines is required (e.g. guidelines from the American College of Chest Physicians6 and the Australasian Society of Thrombosis and Haemostasis).7

CABG, coronary artery bypass surgery; CPB, cardiopulmonary bypass; NSAID, nonsteroidal anti-inflammatory drug; OPCAB, off-pump coronary artery bypass