Antiplatelet therapy in the Perioperative period

                                          Dr. KS DHILLON

Background

Aspirin or clopidogrel is increasingly being used in patients, who are suffering from cardiovascular disease or who are at risk for cardiovascular disease, for the prevention of major adverse events. The number of patients receiving stent implantation continues to increase and hence the need for dual antiplatelet therapy (usually aspirin plus clopidogrel) is also increasing [1].

About 6–8% of patients with dual antiplatelet therapy also need oral anticoagulation due to atrial fibrillation, history of venous thromboembolism, or mechanical heart valves [1].

Furthermore, with an increase in the numbers of the older population, the need for surgery for trauma, degenerative disease, and other conditions is also increasing. 

Physicians are now faced with a dilemma where they have to balance

the risk of perioperative bleeding against the patient’s risk of thrombotic complications.

Unfortunately, for the physicians facing this dilemma, there are no specific, widely accepted, recommendations for the perioperative management of patients who are receiving antiplatelet therapy [1].

The factors which influence a physician’s clinical decision to stop aspirin treatment before surgery are currently not known [2].

Clinical decision making

Perioperative clinical decision making with regard to the cessation of aspirin therapy is quite challenging. Two opposed risks need to be balanced in such situations i.e the risk of cardiovascular thromboembolic complications if aspirin is stopped and the risk of hemorrhagic complications if aspirin is not stopped [2].

This clinical problem is not uncommon. It affects about 250,000 patients yearly in North America [3]. This problem is of interest to several clinicians, including physicians, surgeons, anesthetists, family practitioners as well as dentists. Unfortunately, there is a lack of well-designed clinical trials to inform best practices. There are, however, a large number of methodologically weak observational studies [3].

The US (4) and European (5) guidelines recommend that an individualized risk-benefit analysis is performed prior to elective surgery.

In patients with percutaneous coronary interventions (PCIs) and stents who are on long-term aspirin therapy, the aspirin should be continued perioperatively. In patients where the risk of hemorrhage exceeds the potential cardiovascular benefits, the aspirin has to be stopped [2]. Aspirin has to be stopped in patients undergoing closed space surgery such as intracranial, intramedullary, or posterior chamber of the eye surgery because hemorrhage in such space can have serious deleterious consequences [6,7].

Elective surgery should be postponed in patients who are on dual antiplatelet therapy following a recent PCI [2].

The optimal timing of cessation of aspirin prior to noncardiac surgery remains unclear because there are no large comparative randomized studies to evaluate the optimal timing of aspirin cessation prior to the surgery [2].  

Most guidelines [3,4] recommend that aspirin therapy should be stopped 7 to 10 days before surgery. There are, however, studies [8,9] which show that platelet function recovers 4 days after cessation of aspirin.

It is the expert opinion of some authors that aspirin should be stopped 5 days before surgery and clopidogrel 7 days before surgery [10].

Aspirin administration before surgery and in the early postoperative period does not increase the rate of death or nonfatal myocardial infarction. 

The POISE-2 study [11] which was published in 2014, showed that there was no significant reduction of the composite outcome of death and nonfatal myocardial infarction in patients on perioperative antiplatelet therapy when compared to those who were not on antiplatelet therapy. They found that there was a significant increase in the risk of major bleeding in patients who received 200 mg aspirin perioperatively. The study excluded patients who received a drug-eluting coronary stent less than 1 year before surgery or a bare-metal coronary stent less than 6 weeks before surgery. A large meta-analysis by Burger et al found a 50% increase in bleeding complications in patients on low-dose aspirin in the perioperative period [12].

Death after non-cardiac surgery is often caused by major adverse cardiac events (MACEs). Often aspirin is discontinued preoperatively due to the risk of bleeding despite the existence of evidence that aspirin is useful for the prevention of MACEs. 

Oscarsson et al [13] carried out a randomized, double-blind, placebo-controlled trial to compare the effect of low-dose aspirin with placebo, on myocardial damage, bleeding, and cardiovascular complications in high-risk patients undergoing non-cardiac surgery. They found that perioperative aspirin does reduce the risk of MACE. They also found that there was no increase in the risk of bleeding. Their study, however, was not powered to evaluate bleeding complications. 

Assessing Risk for Bleeding 

There are certain surgeries and procedures which are associated with an increased risk of bleeding when patients are on antiplatelet medications. Some of these surgeries and procedures include [3]: 

• Urologic surgery and procedures--- bladder resection, transurethral prostate resection, tumor ablation, nephrectomy, kidney biopsy, and prostate biopsy. 
• Implantation of a pacemaker or implantable cardioverter-defibrillator device. 
• Sessile colonic polyp resection.
• Surgery and procedures involving highly vascular organs, such as the spleen, kidney, and liver. 
• Bowel resection. 
• Major surgery such as reconstructive plastic surgery, cancer surgery, and joint arthroplasty where there is extensive soft tissue dissection. 
• Cardiac, spinal surgery, or intracranial surgery where bleeding can have serious clinical consequences.

Regional anaesthesia in patients taking anticoagulants

Central neuraxial block is often used in patients undergoing surgery. When using neuraxial blocks, in patients receiving anticoagulants, there are concerns about vertebral canal haematomas.

Spinal haematomas are uncommon following neuraxial anesthesia but their  consequences can be catastrophic. The incidence of spinal haematomas was previously estimated at about 1:150,000 for epidural anaesthesia and 1:220,000 for spinal anaesthesia.  More recent data, however, suggests that the frequency of spinal haematomas is increasing [14]. Spinal haematomas are more common after epidural anesthesia and less common after spinal anesthesia. The overall incidence of spinal haematoma ranges from 1:20,000 to 1:58,000 neuraxial blockades. 

An incidence as high as 1: 4,000 can be seen in patients with indwelling epidural catheters and 1:3,600 in elderly females undergoing orthopaedic surgery under epidural anaesthesia [14]. 

In the presence of impaired coagulation the bleeding incidence increased to 1:40 800 for spinal anesthesia, 1:6,600 for single-shot epidural, and 1:3,100 for epidural catheter techniques [14].

Besides aspirin, other non-steroidal anti-inflammatory drugs have also been associated with spinal haematoma after neuraxial anesthesia. 

The spinal haematomas are of venous origin rather than arterial origin. The spinal haematomas occur in the epidural space where Batson’s venous plexus is present.

Most international guidelines do not consider aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) as a contraindication for neuraxial blocks. 

A consensus document published in 2003 by The American Society of Regional Anesthesia (ASRA), established that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, are considered safe

in neuraxial blockades, both with single shot as well as with catheter techniques [15].

The 2010 European Society of Anaesthesiology (ESA) guidelines, has also established that NSAIDs, including aspirin, do not increase the risk of spinal haematoma and that they are not a contraindication to neuraxial blocks or catheter procedures [16]. 

The 2013 UK guidelines also do not recommend the need for special precautions regarding the use of aspirin in neuraxial anesthetic techniques [17]. 

Generally, aspirin alone is considered to be safe in neuraxial anaesthesia. Concomitant administration of aspirin with another antihaemostatic drugs such as heparin and dual antiplatelet drugs significantly increases the risk of spinal haematomas.

Many patients are on dual antiplatelet therapy with clopidogrel and aspirin. 

In patients going for noncardiac surgery, the current guidelines recommend stopping thienopyridine therapy (ADP receptor antagonists) before elective surgery [14]. 

The recommended time for discontinuation of clopidogrel is 5 to 7 days, of prasugrel is 7 to 10 days and of ticagrelor is 5 to 10 days, before the neuraxial block. Majority of recommendations in noncardiac surgery suggest that clopidogrel should be stopped at least 5 days before the procedure and there are other guidelines which recommend that clopidogrel should be stopped at least 7 days before neuraxial blockade [14].

Conclusion

The cardiologist, surgeon, anesthetist, and the patient must reach a consensus regarding the perioperative management of antiplatelet therapy to minimize the ischemic/thrombotic and bleeding risks. Elective surgery should be delayed where possible for at least 1 month or ideally for 3–6 months from the index cardiac event. 

If the bleeding risk is acceptable, dual antiplatelet therapy should be continued perioperatively, otherwise, thienopyridines (clopidogrel, prasugrel, and ticagrelor) should be discontinued for the minimum amount of time possible and aspirin monotherapy continued. If the bleeding risk is very high, both aspirin and thienopyridine therapy should be interrupted. 

It is safe to continue aspirin in patients undergoing neuraxial spinal and epidural anesthesia. Thienopyridines have to be discontinued for 5 to 10 days before neuraxial anesthesia.

References

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