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Clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi) is a thienopyridine with antiplatelet effects caused by its inhibition of ADP mediated platelet aggregation pathways.1 Both aspirin and clopidogrel have established benefits in the secondary prevention of fatal and non-fatal coronary and cerebrovascular events.1,2 The CURE study has concluded that combining low dose aspirin and clopidogrel in patients with acute coronary syndromes results in additional improvements in outcome over aspirin alone.3 We can therefore expect increasing numbers of ophthalmic patients who have been started on this combined treatment (“COM”).
Departmental concerns were raised by experience with a 76 year old normotensive patient who was on COM. He developed progressive zonular dialysis from unexpected vitreous pressure during standard phacoemulsification. An intracapsular extraction and anterior vitrectomy were required. An iridectomy led to extensive intraoperative hyphaema and vitreous haemorrhage. Postoperative ultrasound confirmed no evidence of choroidal haemorrhage, and the vitreous blood cleared within 3 months to produce 6/6 Snellen acuity with aphakic contact lens correction.
There is a lack of adequate data on the risk of surgery associated ocular bleeding with COM. Clopidogrel taken alone causes less gastrointestinal haemorrhage than aspirin, but has an otherwise similar risk profile to aspirin.4
Post-marketing surveillance of clopidogrel has recorded “conjunctival, ocular, and retinal haemorrhage.” Further information regarding these events, and whether they occurred during ocular surgery, was not available at the time of writing (Nicola Murphy, Sanofi Pharmacovigilance Department, personal communication February 2004).5 A detailed Medline literature search has produced no relevant ophthalmic case experience.
The CURE study found higher “major and minor” bleeding rates in patients taking COM compared with aspirin alone, but showed no increase in life threatening or intracranial haemorrhage, and does not record ocular haemorrhage. Of note is the significant increase in major bleeding events recorded in COM patients undergoing coronary artery bypass graft surgery where the clopidogrel was stopped less than 5 days before the procedure.1
A February 2004 telephonic survey of nursing staff running cataract pre-assessment clinics at 15 ophthalmic units across the United Kingdom indicated variable approaches to such agents. Individual consultants at three units stopped clopidogrel preoperatively. Twelve units continued clopidogrel; none had specific policy for patients on aspirin and clopidogrel. The related and relevant issue of anaesthetists’ approach to regional ocular anaesthesia in patients on such treatment was not addressed.
Translating the CURE study results into a “number needed to treat,” approximately 47 patients with acute coronary syndrome would require treatment for 9 months with aspirin and clopidogrel to prevent one cardiovascular death, non-fatal myocardial infarction, or stroke.3,6 Stopping clopidogrel for a short period is therefore unlikely to make a material difference to the vascular event risk for an individual.
In summary, there is an increased risk of systemic bleeding associated with COM compared to aspirin alone. The degree of perioperative bleeding risk with elective eye surgery is still undefined. Our departmental policy has been changed to stopping clopidogrel for 1 week in patients on combination treatment given for cataract surgery, and to use a similar approach to that normally employed for patients taking aspirin in those on clopidogrel alone. Other departments’ experience with this increasingly used antiplatelet agent would be valued.