8.5.2 Impact of preoperative anticoagulation

 Anticoagulants

It is common for cardiac surgery patients to be on antithrombotics preoperatively. There are several possible scenarios [17].

• Coumarin anticoagulants are stopped 5 days before surgery and replaced by heparin (10,000-15,000 IU/day) from 3^rd preoperative day; aPTT of 1.5 times the baseline value is sought.
• The last dose of subcutaneous LMWH is given 12-24 hours before the procedure.
• An ongoing heparin infusion for unstable coronary syndrome is not stopped before surgery, but continued until the incision; it may also be replaced by a dose of 5,000 IU iv heparin at induction.
• Continuous intravenous heparinisation for more than 3-4 days preoperatively may deplete the body's antithrombin III stores and prevent effective anticoagulation during ECC; treatment is antithrombin III (500-1000 IU), possibly with bags of fresh frozen plasma (see Intraoperative Coagulopathy).
• Mechanical valve prostheses require permanent anticoagulation regardless of position (aortic, mitral or tricuspid); the target INR is 2-2.5 in the aortic position and ≥ 3 in the mitral or tricuspid position. Valve bioprostheses only require AVK anticoagulation for 3 months.
• Before surgery in ECC, the new oral anticoagulants are interrupted for a period corresponding to 3 half-lives of the substance, i.e:
  • Rivaroxaban: 48 hours
  • Apixaban: 48 hours
  • Edoxaban: 48 hours
  • Dabigatran: 48-72 hours.

In patients on anticoagulants or antiplatelets, the dose of heparin used during ECC or OPCAB remains the same as the usual routine (ACT sought: > 450 sec and > 250 sec, respectively), as incomplete inhibition of thrombin may lead to secondary platelet activation [2].

Antiplatelets

Aspirin for secondary prevention (50-160 mg/day) is a lifelong treatment that is never discontinued, even preoperatively. However, in elective cardiac surgery with ECC, it is traditionally recommended to stop aspirin 5 days before surgery because of a 20% increase in bleeding [4]. Stopping it for a longer period does not alter the incidence of bleeding or postoperative cardiac events, but does put the patient at risk of preoperative coronary events, as 2-10% of patients develop acute coronary syndrome 8.5 days after stopping aspirin for secondary prevention [8]. Currently, the latest European guidelines specify that low-dose aspirin (75-160 mg) should be continued in all patients undergoing coronary artery grafting with or without ECC, and should be discontinued for 3-5 days in those at very high risk of bleeding or who refuse transfusions [14]. In any case, the recommendation to discontinue aspirin does not apply to the following situations, where it is continued until the procedure [7]:

• Patients with acute coronary syndrome or unstable angina;
• Coronary stent patients;
• Patients with mechanical valve prostheses or other prosthetic devices;
• Beating heart surgery (without ECC).

Numerous studies have highlighted that aspirin increases bleeding risk only marginally and only with high doses (≥ 325 mg/d), that bleeding events are reduced by antifibrinolytics, and that maintaining aspirin until surgery and restarting it immediately postoperatively reduces in-hospital mortality by 45% in coronary patients [11,15].

Dual therapy (aspirin + clopidogrel) maintained until surgery is an independent predictor of bleeding risk, transfusion requirements, redo surgery for haemostasis and ICU stay. Although the number of blood bags administered (from 1.6 to 3 units) is significantly increased (from 51% to 73% of cases), patient mortality and long-term outcomes do not appear to be affected [12]. A study of 4,794 cases showed that taking clopidogrel < 5 days before surgery did not significantly increase risk of bleeding compared with stopping it > 5 days preoperatively: OR 1.24 for repeat surgery for haemostasis, OR 1.40 for blood transfusions [9]. It also shows another important point: the surgeon performing the operation is the factor most clearly associated with bleeding ! With ticagrelor, the risk of bleeding in CABG is identical to the risk with clopidogrel [16]. In contrast, with prasugrel, which is 10 times more potent than clopidogrel, the risk of bleeding in CABG is increased by 4.7 times [18].

It is usually recommended  clopidogrel to be discontinued for 5 days, ticagrelor for 3-5 days, and prasugrel for 7 days before elective CABG (see Chapter 29, Recommendations for cardiac surgery) [4]. Although conventional, this attitude carries a clear thrombotic risk in exchange for better haemostasis. Some facts demonstrate this.

• In stent recipients, the risk of coronary events increases by 1-2% during discontinuation, but can be as high as 2% per day in the case of acute coronary syndrome (ACS) [12].
• Maintaining clopidogrel up to 24 hours preoperatively significantly reduces the rate of infarction at 1 year (OR 0.57-0.63) [1,12].
• Comparison of ticagrelor and clopidogrel showed that shortening the antiplatelet-free period reduced mortality after CABG (HR 0.49) as ticagrelor was stopped 24-72 hours before surgery and clopidogrel was stopped >5 days before surgery. However, there was no difference in mortality between the two drugs if they were stopped the day before surgery or more than 5 days before surgery [6]. Thus, it is the duration of discontinuation that makes the difference.

As with aspirin alone, dual therapy is not interrupted when prescribed for unstable coronary syndrome or during the re-endothelialisation phase of stents (passive stents: minimum 6 weeks; active stents 1^st generation: ≥ 6 months; active 2^nd generation stents: 3 months). In these situations, it should be continued until 24-48 hours before surgery. When the duration of preoperative discontinuation is debated, a platelet aggregability test is valuable as its results often shorten time between surgery and the last clopidogrel dose without increasing blood loss [13]. Patients whose platelets retain some residual activity on dual antiplatelet therapy have less postoperative major bleeding. The duration of interruption of antiplatelet therapy can therefore be reduced, as a poor responder bleeds less than a normal individual. Thus, the average waiting time before CABGs could be reduced to 2.7 days without increasing risk of bleeding in patients with satisfactory residual aggregability on preoperative testing [10]. Intraoperative antifibrinolytics reduce the risk of bleeding in patients on antiplatelet agents. Beating heart revascularisation, which requires less heparinisation, is particularly indicated in these circumstances because it is less haemorrhagic [7].

Emergency rescue CABG

 The situation is delicate in emergency coronary artery bypass grafting (CABG) for acute coronary syndrome, because a loading dose of clopidogrel (300-600 mg) or ticagrelor (180 mg) is recommended even before coronary angiography, i.e. before knowing whether the patient is likely to undergo emergency or semi-emergency surgical revascularisation (0.3-0.5% of PCI) [2]. Avoiding this medication puts potential CABG patients at too great a risk of coronary thrombosis in medical treatment or PCI with stenting, but burdens potential CABG patients with significant bleeding morbidity: the incidence of major bleeding is 11-47% after 300 mg and 73% after 600 mg of clopidogrel, but is almost five times higher after 60 mg of prasugrel [3,18]. Emergency angioplasty, without prior knowledge of coronary anatomy, is an excellent indication for ticagrelor, a potent, rapid and reversible blocker with less intraoperative blood loss than other substances. When CABG is performed in the setting of an acute coronary syndrome, aspirin and clopidogrel or ticagrelor are not interrupted for more than 24-48 hours; they should be resumed as soon as possible in the postoperative period and continued for at least 6 months (see Chapter 29, Recommendations for cardiac surgery) [2,5].

 © CHASSOT PG, MARCUCCI Carlo, last update November 2019.

References

1. BIANCARI F, AIRAKSINEN KEJ, LIP GYH. Benefits and risks of using clopidogrel before coronary artery ECC: Systemic review and meta-analysis od randomized trials and observational studies. J Thorac Cardiovasc Surg 2012; 143:665-75
2. BROWN  C, JOSHI B, FARADAY N, et al. Emergency cardiac surgery in patients with acute coronary syndromes: a review of the evidence and perioperative implications of medical and mechanical therapeutics. Anesth Analg 2011; 112: 277-99
3. CRUDEN NL, MORCH K, WONG DR, et al. Clopidogrel loading dose and bleeding outcomes in patients undergoing urgent cronary artery bypass graTFing. Am Heart J 2011; 161:404-10
4. DUNNING J, VERSTEEGH M, FABBRI A, et al. Guidelines on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 2008; 34:73-92
5. HAMM CW, BASSAND JP, AGEWALL S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2011; 32:2999-3054
6. HELD C, ASENBLAD N, BASSAND JP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery ECC. J Am Coll Cardiol 2011; 57:672-84
7. HILLIS LD, SMITH PK, ANDERSON JL, et al. 2011 ACCF/AHA Guideline for coronary artery bypass graTF surgery. J Am Coll Cardiol 2011; 58:e123-e210
8. JACOB M, SMEDIRA N, BLACKSTONE E, et al. Effect of timing of chronic preoperative aspirin discontinuation on morbidity and mortality in coronary artery ECC. Circulation 2011; 123:577-83
9. KIM JHJ, NEWBY LK, CLARE RM, et al. Clopidogrel use and bleedingaftercoronary artery bypass graTF surgery. Am Heart J 2008; 156:886-92
10. MAHLA  E, Suarez TA, Bliden KP, et al. Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graTF surgery. Circ Cardiovasc Interv 2012; 5:261-9
11. McILLROY DR, MYLES OS, PHILLIPS LE, SMITH JA. Antifibrinolytics in cardiac surgical patients receiving aspirin: a systematic review and meta-analysis. Br J Anaesth 2009; 102:168-78
12. NIJJER S, WATSON G, ATHANASIOU T, et al. Safety of clopidogrel being continued until the time of coronary artery bypass graTFing in patients with acute coronary syndrome: a meta-analysis of 34 studies. Eur Heart J 2011; 32:2970-88
13. RANUCCI M, BARYSHNIKOVA E, SORO G, et al. Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery patients receiving thienopyridines. Ann Thorac Surg 2011; 91:123-30
14. 14SOUSA-UVA  M, STOREY R, HUBER K, et al. Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery ECC. Eur Heart J 2014; 35:1510-4
15. SUN JC, WHITLOCK R, CHENG J, et al. The effect of preoperative aspirin on bleeding, transfusion, myocardial infarction, and mortality in coronary artery ECC: a systematic review of randomized and observational studies. Eur Heart J 2008; 29:1057-71
16. WALLENTIN  L, BECKER RC, BUDAJ A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361:1045-57
17. WEBER CF, KLAGES M, ZACHAROWSKI K. Perioperative coagulation management during cardiac surgery. Curr Opin Anaesthesiol 2013; 26: 60-84
18. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357:2001-15