Introduction
Antiplatelets
Anticoagulants
Conclusions
References

 

 

 

 

 

Introduction

Secondary prevention of ischaemic strokes revolves around use of antiplatelet medication in nonembolic and anticoagulation in embolic strokes, the most common of which is atrial fibrillation. Current guidelines recommend lifelong clopidogrel as the antiplatelet of choice; however, occasionally due to allergies or intolerance 75mg aspirin is preferred. With regards to atrial fibrillation the choice is between warfarin and the newer direct oral anti-coagulants (DOACs).

With more patients surviving myocardial infarctions and strokes than ever before, prescriptions for antiplatelets and anticoagulation have never been higher. Difficulties, however, arise when these require cessation due to surgery or other procedures with no consensus on length of cessation or bridging therapies. With this in mind we have searched the literature for evidence on cessation to create easy to use guidelines for physicians and surgeons prior to patient procedures.

 

Antiplatelets

With regards to non-embolic strokes, clopidogrel is the antiplatelet of choice for secondary prevention having been established in the CAPRIE trial1 with aspirin being the second-line choice in those intolerant to clopidogrel. Historically, aspirin appears to be safe during surgery or other procedures and so we would recommend continuing this throughout the peri-operative period. Further evidence for continued use comes from Gerstein et al in their paper discussing the aspirin withdrawal syndrome,2 which whilst focusing on increased risk of cardiovascular events must hypothetically also suggest increased risk of further cerebral events.

With regards to clopidogrel, evidence is available that its use seven days prior to invasive cardiac3 or intra-abdominal surgery4 is associated with an increased bleeding risk and need for blood transfusion; however, this same risk does not always extend to minor non-invasive procedures.5 Along with bleeding risk, cardiovascular risk must also be considered prior to stopping clopidogrel in high risk patients (considered to be those who have recently suffered a myocardial infarction or stroke, undergone percutaneous coronary angioplasty within the last six weeks or those with a drug eluting stent within the last 12 weeks). In these patients we would simply advise postponing the procedure and continue usual antiplatelets.

All other patients would be considered for surgery and our guidance here would be to stop clopidogrel for seven days prior to surgery, but bridge with aspirin 75mg. This strategy best counters risk of cardiovascular events verses bleeding. Clopidogrel can safely be restarted once haemostasis has been achieved.

Newer antiplatelets have recently been developed, but the evidence of cessation is lacking and so we have made no recommendations here.

 

Anticoagulants

Oral anticoagulation is the preferred treatment of embolic strokes. Previously, the only option was vitamin K antagonists with warfarin the usual choice. These work by inhibiting the vitamin K dependent coagulation factors: II, VII, IX and X. However, they have a narrow therapeutic window and require regular monitoring of prothrombin time with the International Normalised Ratio (INR) blood test. Matchar et al6 have also shown that patients spend less than two thirds of the time in the therapeutic INR window and so even patients thought to be adequately anticoagulated are spending a significant time with inadequate anticoagulation.

 

ADVICE SURROUNDING ANTIPLATELET AND ANTICOAGULATION CESSATION
  • Historical evidence suggests aspirin is safe and can be continued. Clopidogrel is associated with increased risk of bleeding and should be held for seven days prior to any invasive procedure with aspirin 75mg as a bridging therapy.
  • Anticoagulant use has split into vitamin K antagonists, namely warfarin, and direct oral anticoagulants (DOACs). A risk assessment should then be completed for thromboembolic risk prior to stopping.
  • Warfarin must be held for five days to allow correction of INR. Patients at low risk of thromboembolic events can remain off any anticoagulation until after their procedure whilst high risk patients require bridging with low molecular weight heparin. This is held the day prior to procedure and restarted once haemostasis has been achieved.
  • With DOACs bleeding risk is more important as they are metabolised out of the system within a few days. In low bleeding risk procedures all DOACs can be safely continued otherwise guidance varies according to the DOAC.
  • Rivaroxaban and apixaban are held for 48 hours prior to a high risk procedure and 24-36 hours to a medium risk procedure according to creatinine clearance. Dabigitran is divided into three groups for creatinine clearance, but cessation ranges from 24-96 hours depending on bleeding risk and creatinine clearance.

 

Recently, use of vitamin K antagonists have been superseded by the DOACs.7 These have the benefit of being one dose for all patients and so no monitoring of levels is required. Three studies (Re-ly,8 Rocket9 and Aristotle10) have shown non-inferiority between warfarin and NOACs with reduced stroke risk in patients treated with high-dose dabigitran. Negatives include increased risk of gastrointestinal bleeds and no antidote yet to apixaban or rivaroxaban, though this may change in the next few years.

With regards to temporarily stopping these medications the patient must first be risk assessed for thrombotic risk whilst off anticoagulation. All patients should stop warfarin five days prior to surgery and low thromboembolic risk patients can remain off any anticoagulation until after the surgery when their warfarin can be restarted. High risk patients require bridging with low molecular weight heparin (LMWH) whilst off oral anticoagulation which ideally should start on day three off warfarin. LMWH should be held for 24 hours prior to surgery and restarted after surgery along with warfarin until the INR is therapeutic.

Patients with an intermediate risk of thromboembolic disease off warfarin should be further risk assessed according to their bleeding risk during the procedure to help guide cessation plans. Those undergoing procedures deemed high risk of bleeding can follow the low risk strategy of simply holding warfarin whilst conversely those deemed low risk of bleeding are guided along the high risk of thromboembolic disease group and bridged with heparin. Following surgery all patients should restart warfarin the same day. Figure 1 helps risk stratify patients for thromboembolic disease.

 

Figure 1. Cessation of warfarin and antiplatelets

 

DOACs by their nature are completely out of the system within a few days and this creates an advantage when temporarily holding these. Here bleeding risk (Figure 2) is more important when deciding how long to hold these prior to any procedure. For low risk procedures all DOACs can be safely continued, but for medium and high risk procedures length of cessation depends on the choice of DOAC.

Rivaroxaban and apixaban are fairly easy to follow with high risk procedures being held for 48 hours and medium risk for 24–36 hours depending on creatinine clearance or estimated Glomerular Filtration Rate (eGFR). Dabigitran is slightly more complicated due to three different groups for creatinine clearance, but cessation ranges from 24–96 hours prior to surgery depending on risk of bleeding and creatinine clearance. Further guidance can be found in Figure 2. All DOACs can be safely restarted once haemostasis has been achieved.

We have condensed the above information into simple infographs which we believe are easy to follow for real world scenarios of cessation of anticoagulants or antiplatelets.

 

Figure 2. Cessation of DOACs

 

Conclusion

Increasing numbers of patients are requiring antiplatelets or anticoagulants for secondary prevention of cardio and cerebrovascular events. Using available literature we feel this guidance provides up-to-date advice on cessation of these medications pre-intervention along with advice on when to restart them best balancing the risk of ischaemic event verses risk of bleed from the intervention. Finally, we have developed an easy to use infograph of our recommendations for clinicians to follow faced with these scenarios.

 

Dr Natalie McNeela, ST5 Geriatrics Registrar, Cannock Chase Hospital,

Dr Meena, Srinivasan Consultant Stroke Physician,

Victoria Barker, FY2 Doctor,

Royal Wolverhampton NHS Trust, Princess Royal Hospital Telford.

 

Conflict of interest: none declared

 


References

1. CAPRIE steering committee. A randomised, blinded trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events. Lancet 1996; 348(9038): 1329–39

2. Gerstein NS, Schulman PM, Gerstein WH, et al. Should more patients continue aspirin therapy perioperatively?: clinical impact of aspirin withdrawal syndrome. Ann Surg 2012; 255(5): 811-19

3. Mariscalco G, Bruno VD, Cottini M, et al. Optimal timing of discontinuation of clopidogrel and risk of blood transfusion after coronary surgery. Propensity score analysis. Circ J 2011; 75(12): 2805–12

4. Chernoguz A, Telem DA, Chu E, et al. Cessation of clopidogrel before major abdominal procedures. Arch Surg 2011;146(3): 334–39 Figure 2. Cessation of DOACs

5. Chu EW, Telem DA, Chernoguz A, Divino CM. Assessing the risk of clopidogrel-related bleeding complications in patients undergoing inguinal herniorrhaphy. Hernia 2011; 15(1): 31–5

6. Matchar DB, Samsa GP, Cohen SJ, et al. Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial. Am J Med 2002; 113: 42–51

7. Huisman MV, Rothman KJ, Paquette M, et al. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2. J Am Coll Cardiol 2017; 69(7): 777–85

8. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361: 1139–15

9. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 2011; 365: 883–91

10. Granger CB, Alexander JH, McMurray JJV et al. Apixaban verses warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981–99