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Should we stop aspirin before noncardiac surgery?
Author(s)
Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Christopher Whinney, MD

In patients with cardiac stents, do not stop aspirin. If the risk of bleeding outweighs the benefit (eg, with intracranial procedures), an informed discussion involving the surgeon, cardiologist, and patient is critical to ascertain risks vs benefits.

See related editorial

In patients using aspirin for secondary prevention, the decision depends on the patient’s cardiac status and an assessment of risk vs benefit. Aspirin has no role in patients undergoing noncardiac surgery who are at low risk of a major adverse cardiac event.1,2

Aspirin used for secondary prevention reduces rates of death from vascular causes,3 but data on the magnitude of benefit in the perioperative setting are still evolving. In patients with coronary stents, continuing aspirin is beneficial,4,5 whereas stopping it is associated with an increased risk of acute stent thrombosis, which causes significant morbidity and mortality.6

SURGERY AND THROMBOTIC RISK: WHY CONSIDER ASPIRIN?

The Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study7 prospectively screened 15,133 patients for myocardial injury with troponin T levels daily for the first 3 consecutive postoperative days; 1,263 (8%) of the patients had a troponin elevation of 0.03 ng/mL or higher. The 30-day mortality rate in this group was 9.8%, compared with 1.1% in patients with a troponin T level of less than 0.03 ng/mL (odds ratio 10.07; 95% confidence interval [CI] 7.84–12.94; P < .001).8 The higher the peak troponin T concentration, the higher the risk of death within 30 days:

  • 0.01 ng/mL or less, risk 1.0%
  • 0.02 ng/mL, risk 4.0%
  • 0.03 to 0.29 ng/mL, risk 9.3%
  • 0.30 ng/mL or greater, risk 16.9%.7

Myocardial injury is a common postoperative vascular complication.7 Myocardial infarction (MI) or injury perioperatively increases the risk of death: 1 in 10 patients dies within 30 days after surgery.8

Surgery creates substantial physiologic stress through factors such as fasting, anesthesia, intubation, surgical trauma, extubation, and pain. It promotes coagulation9 and inflammation with activation of platelets,10 potentially leading to thrombosis.11 Coronary thrombosis secondary to plaque rupture11,12 can result in perioperative MI. Perioperative hemodynamic variability, anemia, and hypoxia can lead to demand-supply mismatch and also cause cardiac ischemia.

Aspirin is an antiplatelet agent that irreversibly inhibits platelet aggregation by blocking the formation of cyclooxygenase. It has been used for several decades as an antithrombotic agent in primary and secondary prevention. However, its benefit in primary prevention is uncertain, and the magnitude of antithrombotic benefit must be balanced against the risk of bleeding.

The Antithrombotic Trialists’ Collaboration13 performed a systematic review of 6 primary prevention trials involving 95,000 patients and found that aspirin therapy was associated with a 12% reduction in serious vascular events, which occurred in 0.51% of patients taking aspirin per year vs 0.57% of controls (P = .0001). However, aspirin also increased the risk of major bleeding, at a rate of 0.10% vs 0.07% per year (P < .0001), with 2 bleeding events for every avoided vascular event.13

WILL ASPIRIN PROTECT PATIENTS AT CARDIAC RISK?

The second Perioperative Ischemic Evaluation trial (POISE 2),1 in patients with atherosclerotic disease or at risk for it, found that giving aspirin in the perioperative period did not reduce the rate of death or nonfatal MI, but increased the risk of a major bleeding event.

The trial included 10,010 patients undergoing noncardiac surgery who were randomly assigned to receive aspirin or placebo. The aspirin arm included 2 groups: patients who were not on aspirin (initiation arm), and patients on aspirin at the time of randomization (continuation arm).

Death or nonfatal MI (the primary outcome) occurred in 7.0% of patients on aspirin vs 7.1% of patients receiving placebo (hazard ratio [HR] 0.99, 95% CI 0.86–1.15, P = .92). The risk of major bleeding was 4.6% in the aspirin group vs 3.8% in the placebo group (HR 1.23, 95% CI 1.01–1.49, P = .04).1

George et al,14 in a prospective observational study in a single tertiary care center, found that fewer patients with myocardial injury in noncardiac surgery died if they took aspirin or clopidogrel postoperatively. Conversely, lack of antithrombotic therapy was an independent predictor of death (P < .001). The mortality rate in patients with myocardial injury who were on antithrombotic therapy postoperatively was 6.7%, compared with 12.1% in those without postoperative antithrombotic therapy (estimated number needed to treat, 19).14

 

 

PATIENTS WITH CORONARY STENTS UNDERGOING NONCARDIAC SURGERY

Percutaneous coronary intervention (PCI) accounts for 3.6% of all operating-room procedures in the United States,15 and 20% to 35% of patients who undergo PCI undergo noncardiac surgery within 2 years of stent implantation.16,17

Antiplatelet therapy is discontinued in about 20% of patients with previous PCI who undergo noncardiac surgery.18

Observational data have shown that stopping antiplatelet therapy in patients with previous PCI with stent placement who undergo noncardiac surgery is the single most important predictor of stent thrombosis and death.19–21 The risk increases if the interval between stent implantation and surgery is shorter, especially within 180 days.16,17 Patients who have stent thrombosis are at significantly higher risk of death.

Graham et al4 conducted a subgroup analysis of the POISE 2 trial comparing aspirin and placebo in 470 patients who had undergone PCI (427 had stent placement, and the rest had angioplasty or an unspecified type of PCI); 234 patients received aspirin and 236 placebo. The median time from stent implantation to surgery was 5.3 years.

Of the patients in the aspirin arm, 14 (6%) had the primary outcome of death or nonfatal MI compared with 27 patients (11.5%) in the placebo arm (absolute risk reduction 5.5%, 95% CI 0.4%–10.5%). The result, which differed from that in the primary trial,1 was due to reduction in MI in the PCI subgroup on aspirin. PCI patients who were on aspirin did not have increased bleeding risk. This subgroup analysis, albeit small and limited, suggests that continuing low-dose aspirin in patients with previous PCI, irrespective of the type of stent or the time from stent implantations, minimizes the risk of perioperative MI.

GUIDELINES AND RECOMMENDATIONS

Routine perioperative use of aspirin increases the risk of bleeding without a reduction in ischemic events.1 Patients with prior PCI are at increased risk of acute stent thrombosis when antiplatelet medications are discontinued.20,21 Available data, although limited, support continuing low-dose aspirin without interruption in the perioperative period in PCI patients,4 as do the guidelines from the American College of Cardiology.5

Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.
Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.

We propose a management algorithm for patients undergoing noncardiac surgery on antiplatelet therapy that takes into consideration whether the surgery is urgent, elective, or time-sensitive (Figure 1). It is imperative to involve the cardiologist, surgeon, anesthesiologist, and the patient in the decision-making process.

In the perioperative setting for patients undergoing noncardiac surgery:

  • Discontinue aspirin in patients without coronary heart disease, as bleeding risk outweighs benefit.
  • Consider aspirin in patients at high risk for a major adverse cardiac event if benefits outweigh risk.
  • Continue low-dose aspirin without interruption in patients with a coronary stent, irrespective of the type of stent.
  • If a patient has had PCI with stent placement but is not currently on aspirin, talk with the patient and the treating cardiologist to find out why, and initiate aspirin if no contraindications exist.
References
  1. Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370(16):1494–1503. doi:10.1056/NEJMoa1401105
  2. Fleisher LA, Fleischmann KE, Auerbach AD, et al; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2014; 64(22):e77–e137. doi:10.1016/j.jacc.2014.07.944
  3. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994; 308(6921):81–106. pmid:8298418
  4. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery. Ann Intern Med 2018; 168(4):237–244. doi:10.7326/M17-2341
  5. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 68(10):1082–1115. doi:10.1016/j.jacc.2016.03.513
  6. Albaladejo P, Marret E, Samama CM, et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart 2011; 97(19):1566–1572. doi:10.1136/hrt.2011.224519
  7. Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA 2012; 307(21):2295–2304. doi:10.1001/jama.2012.5502
  8. Botto F, Alonso-Coello P, Chan MT, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology 2014; 120(3):564–578. doi:10.1097/ALN.0000000000000113
  9. Gorka J, Polok K, Iwaniec T, et al. Altered preoperative coagulation and fibrinolysis are associated with myocardial injury after non-cardiac surgery. Br J Anaesth 2017; 118(5):713–719. doi:10.1093/bja/aex081
  10. Rajagopalan S, Ford I, Bachoo P, et al. Platelet activation, myocardial ischemic events and postoperative non-response to aspirin in patients undergoing major vascular surgery. J Thromb Haemost 2007; 5(10):2028–2035. doi:10.1111/j.1538-7836.2007.02694.x
  11. Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004; 93(1):9–20. doi:10.1093/bja/aeh147
  12. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ 2005; 173(6):627–634. doi:10.1503/cmaj.050011
  13. Antithrombotic Trialists’ (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373(9678):1849–1860. doi:10.1016/S0140-6736(09)60503-1
  14. George R, Menon VP, Edathadathil F, et al. Myocardial injury after noncardiac surgery—incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre. Medicine (Baltimore) 2018; 97(19):e0402. doi:10.1097/MD.0000000000010402
  15. Weiss AJ, Elixhauser A, Andrews RM; Healthcare Cost and Utilization Project (HCUP). Characteristics of operating room procedures in US hospitals, 2011: statistical brief #170. https://hcup-us.ahrq.gov/reports/statbriefs/sb170-Operating-Room-Procedures-United-States-2011.jsp. Accessed May 3, 2019.
  16. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013; 310(14):1462–1472. doi:10.1001/jama.2013.278787
  17. Wijeysundera DN, Wijeysundera HC, Yun L, et al. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation 2012; 126(11):1355–1362. doi:10.1161/CIRCULATIONAHA.112.102715
  18. Rossini R, Capodanno D, Lettieri C, et al. Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011; 107(2):186–194. doi:10.1016/j.amjcard.2010.08.067
  19. Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009; 119(12):1634–1642. doi:10.1161/CIRCULATIONAHA.108.813667
  20. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17):2126–2130. doi:10.1001/jama.293.17.2126
  21. Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006; 98(3):352–356. doi:10.1016/j.amjcard.2006.02.039
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prabhakaran_aspirinandnoncardiacsurgery.pdf
Author and Disclosure Information

Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Christopher Whinney, MD, SFHM, FACP
Chairman, Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Address: Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP, Department of Hospital Medicine, M2 Annex, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195; prabhak@ccf.org

Issue
Cleveland Clinic Journal of Medicine - 86(8)
Publications
Cleveland Clinic Journal of Medicine
Topics
Drug Therapy
Hospital Medicine
Cardiology
Page Number
518-521
Legacy Keywords
aspirin, surgery, perioperative medication, prevention, stent thrombosis, VISION study, POISE study, myocardial injury after noncardiac surgery, MINS, bleeding, percutaneous coronary intervention, antiplatelet therapy, Anbazhagan Prabhakaran, Christopher Whinney
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Author(s)
Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Christopher Whinney, MD
Author(s)
Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Christopher Whinney, MD
Author and Disclosure Information

Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Christopher Whinney, MD, SFHM, FACP
Chairman, Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Address: Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP, Department of Hospital Medicine, M2 Annex, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195; prabhak@ccf.org

Author and Disclosure Information

Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP
Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Christopher Whinney, MD, SFHM, FACP
Chairman, Department of Hospital Medicine, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Cleveland, OH

Address: Anbazhagan Prabhakaran, MD, MRCP (Edin), FACP, Department of Hospital Medicine, M2 Annex, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195; prabhak@ccf.org

Article PDF
prabhakaran_aspirinandnoncardiacsurgery.pdf
Article PDF
prabhakaran_aspirinandnoncardiacsurgery.pdf
Related Articles
Aspirin: 4,000 years and still learning
Perioperative medication management: General principles and practical applications
Should patients stop taking aspirin for primary prevention?
Aspirin: Its risks, benefits, and optimal use in preventing cardiovascular events

In patients with cardiac stents, do not stop aspirin. If the risk of bleeding outweighs the benefit (eg, with intracranial procedures), an informed discussion involving the surgeon, cardiologist, and patient is critical to ascertain risks vs benefits.

See related editorial

In patients using aspirin for secondary prevention, the decision depends on the patient’s cardiac status and an assessment of risk vs benefit. Aspirin has no role in patients undergoing noncardiac surgery who are at low risk of a major adverse cardiac event.1,2

Aspirin used for secondary prevention reduces rates of death from vascular causes,3 but data on the magnitude of benefit in the perioperative setting are still evolving. In patients with coronary stents, continuing aspirin is beneficial,4,5 whereas stopping it is associated with an increased risk of acute stent thrombosis, which causes significant morbidity and mortality.6

SURGERY AND THROMBOTIC RISK: WHY CONSIDER ASPIRIN?

The Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study7 prospectively screened 15,133 patients for myocardial injury with troponin T levels daily for the first 3 consecutive postoperative days; 1,263 (8%) of the patients had a troponin elevation of 0.03 ng/mL or higher. The 30-day mortality rate in this group was 9.8%, compared with 1.1% in patients with a troponin T level of less than 0.03 ng/mL (odds ratio 10.07; 95% confidence interval [CI] 7.84–12.94; P < .001).8 The higher the peak troponin T concentration, the higher the risk of death within 30 days:

  • 0.01 ng/mL or less, risk 1.0%
  • 0.02 ng/mL, risk 4.0%
  • 0.03 to 0.29 ng/mL, risk 9.3%
  • 0.30 ng/mL or greater, risk 16.9%.7

Myocardial injury is a common postoperative vascular complication.7 Myocardial infarction (MI) or injury perioperatively increases the risk of death: 1 in 10 patients dies within 30 days after surgery.8

Surgery creates substantial physiologic stress through factors such as fasting, anesthesia, intubation, surgical trauma, extubation, and pain. It promotes coagulation9 and inflammation with activation of platelets,10 potentially leading to thrombosis.11 Coronary thrombosis secondary to plaque rupture11,12 can result in perioperative MI. Perioperative hemodynamic variability, anemia, and hypoxia can lead to demand-supply mismatch and also cause cardiac ischemia.

Aspirin is an antiplatelet agent that irreversibly inhibits platelet aggregation by blocking the formation of cyclooxygenase. It has been used for several decades as an antithrombotic agent in primary and secondary prevention. However, its benefit in primary prevention is uncertain, and the magnitude of antithrombotic benefit must be balanced against the risk of bleeding.

The Antithrombotic Trialists’ Collaboration13 performed a systematic review of 6 primary prevention trials involving 95,000 patients and found that aspirin therapy was associated with a 12% reduction in serious vascular events, which occurred in 0.51% of patients taking aspirin per year vs 0.57% of controls (P = .0001). However, aspirin also increased the risk of major bleeding, at a rate of 0.10% vs 0.07% per year (P < .0001), with 2 bleeding events for every avoided vascular event.13

WILL ASPIRIN PROTECT PATIENTS AT CARDIAC RISK?

The second Perioperative Ischemic Evaluation trial (POISE 2),1 in patients with atherosclerotic disease or at risk for it, found that giving aspirin in the perioperative period did not reduce the rate of death or nonfatal MI, but increased the risk of a major bleeding event.

The trial included 10,010 patients undergoing noncardiac surgery who were randomly assigned to receive aspirin or placebo. The aspirin arm included 2 groups: patients who were not on aspirin (initiation arm), and patients on aspirin at the time of randomization (continuation arm).

Death or nonfatal MI (the primary outcome) occurred in 7.0% of patients on aspirin vs 7.1% of patients receiving placebo (hazard ratio [HR] 0.99, 95% CI 0.86–1.15, P = .92). The risk of major bleeding was 4.6% in the aspirin group vs 3.8% in the placebo group (HR 1.23, 95% CI 1.01–1.49, P = .04).1

George et al,14 in a prospective observational study in a single tertiary care center, found that fewer patients with myocardial injury in noncardiac surgery died if they took aspirin or clopidogrel postoperatively. Conversely, lack of antithrombotic therapy was an independent predictor of death (P < .001). The mortality rate in patients with myocardial injury who were on antithrombotic therapy postoperatively was 6.7%, compared with 12.1% in those without postoperative antithrombotic therapy (estimated number needed to treat, 19).14

 

 

PATIENTS WITH CORONARY STENTS UNDERGOING NONCARDIAC SURGERY

Percutaneous coronary intervention (PCI) accounts for 3.6% of all operating-room procedures in the United States,15 and 20% to 35% of patients who undergo PCI undergo noncardiac surgery within 2 years of stent implantation.16,17

Antiplatelet therapy is discontinued in about 20% of patients with previous PCI who undergo noncardiac surgery.18

Observational data have shown that stopping antiplatelet therapy in patients with previous PCI with stent placement who undergo noncardiac surgery is the single most important predictor of stent thrombosis and death.19–21 The risk increases if the interval between stent implantation and surgery is shorter, especially within 180 days.16,17 Patients who have stent thrombosis are at significantly higher risk of death.

Graham et al4 conducted a subgroup analysis of the POISE 2 trial comparing aspirin and placebo in 470 patients who had undergone PCI (427 had stent placement, and the rest had angioplasty or an unspecified type of PCI); 234 patients received aspirin and 236 placebo. The median time from stent implantation to surgery was 5.3 years.

Of the patients in the aspirin arm, 14 (6%) had the primary outcome of death or nonfatal MI compared with 27 patients (11.5%) in the placebo arm (absolute risk reduction 5.5%, 95% CI 0.4%–10.5%). The result, which differed from that in the primary trial,1 was due to reduction in MI in the PCI subgroup on aspirin. PCI patients who were on aspirin did not have increased bleeding risk. This subgroup analysis, albeit small and limited, suggests that continuing low-dose aspirin in patients with previous PCI, irrespective of the type of stent or the time from stent implantations, minimizes the risk of perioperative MI.

GUIDELINES AND RECOMMENDATIONS

Routine perioperative use of aspirin increases the risk of bleeding without a reduction in ischemic events.1 Patients with prior PCI are at increased risk of acute stent thrombosis when antiplatelet medications are discontinued.20,21 Available data, although limited, support continuing low-dose aspirin without interruption in the perioperative period in PCI patients,4 as do the guidelines from the American College of Cardiology.5

Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.
Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.

We propose a management algorithm for patients undergoing noncardiac surgery on antiplatelet therapy that takes into consideration whether the surgery is urgent, elective, or time-sensitive (Figure 1). It is imperative to involve the cardiologist, surgeon, anesthesiologist, and the patient in the decision-making process.

In the perioperative setting for patients undergoing noncardiac surgery:

  • Discontinue aspirin in patients without coronary heart disease, as bleeding risk outweighs benefit.
  • Consider aspirin in patients at high risk for a major adverse cardiac event if benefits outweigh risk.
  • Continue low-dose aspirin without interruption in patients with a coronary stent, irrespective of the type of stent.
  • If a patient has had PCI with stent placement but is not currently on aspirin, talk with the patient and the treating cardiologist to find out why, and initiate aspirin if no contraindications exist.

In patients with cardiac stents, do not stop aspirin. If the risk of bleeding outweighs the benefit (eg, with intracranial procedures), an informed discussion involving the surgeon, cardiologist, and patient is critical to ascertain risks vs benefits.

See related editorial

In patients using aspirin for secondary prevention, the decision depends on the patient’s cardiac status and an assessment of risk vs benefit. Aspirin has no role in patients undergoing noncardiac surgery who are at low risk of a major adverse cardiac event.1,2

Aspirin used for secondary prevention reduces rates of death from vascular causes,3 but data on the magnitude of benefit in the perioperative setting are still evolving. In patients with coronary stents, continuing aspirin is beneficial,4,5 whereas stopping it is associated with an increased risk of acute stent thrombosis, which causes significant morbidity and mortality.6

SURGERY AND THROMBOTIC RISK: WHY CONSIDER ASPIRIN?

The Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study7 prospectively screened 15,133 patients for myocardial injury with troponin T levels daily for the first 3 consecutive postoperative days; 1,263 (8%) of the patients had a troponin elevation of 0.03 ng/mL or higher. The 30-day mortality rate in this group was 9.8%, compared with 1.1% in patients with a troponin T level of less than 0.03 ng/mL (odds ratio 10.07; 95% confidence interval [CI] 7.84–12.94; P < .001).8 The higher the peak troponin T concentration, the higher the risk of death within 30 days:

  • 0.01 ng/mL or less, risk 1.0%
  • 0.02 ng/mL, risk 4.0%
  • 0.03 to 0.29 ng/mL, risk 9.3%
  • 0.30 ng/mL or greater, risk 16.9%.7

Myocardial injury is a common postoperative vascular complication.7 Myocardial infarction (MI) or injury perioperatively increases the risk of death: 1 in 10 patients dies within 30 days after surgery.8

Surgery creates substantial physiologic stress through factors such as fasting, anesthesia, intubation, surgical trauma, extubation, and pain. It promotes coagulation9 and inflammation with activation of platelets,10 potentially leading to thrombosis.11 Coronary thrombosis secondary to plaque rupture11,12 can result in perioperative MI. Perioperative hemodynamic variability, anemia, and hypoxia can lead to demand-supply mismatch and also cause cardiac ischemia.

Aspirin is an antiplatelet agent that irreversibly inhibits platelet aggregation by blocking the formation of cyclooxygenase. It has been used for several decades as an antithrombotic agent in primary and secondary prevention. However, its benefit in primary prevention is uncertain, and the magnitude of antithrombotic benefit must be balanced against the risk of bleeding.

The Antithrombotic Trialists’ Collaboration13 performed a systematic review of 6 primary prevention trials involving 95,000 patients and found that aspirin therapy was associated with a 12% reduction in serious vascular events, which occurred in 0.51% of patients taking aspirin per year vs 0.57% of controls (P = .0001). However, aspirin also increased the risk of major bleeding, at a rate of 0.10% vs 0.07% per year (P < .0001), with 2 bleeding events for every avoided vascular event.13

WILL ASPIRIN PROTECT PATIENTS AT CARDIAC RISK?

The second Perioperative Ischemic Evaluation trial (POISE 2),1 in patients with atherosclerotic disease or at risk for it, found that giving aspirin in the perioperative period did not reduce the rate of death or nonfatal MI, but increased the risk of a major bleeding event.

The trial included 10,010 patients undergoing noncardiac surgery who were randomly assigned to receive aspirin or placebo. The aspirin arm included 2 groups: patients who were not on aspirin (initiation arm), and patients on aspirin at the time of randomization (continuation arm).

Death or nonfatal MI (the primary outcome) occurred in 7.0% of patients on aspirin vs 7.1% of patients receiving placebo (hazard ratio [HR] 0.99, 95% CI 0.86–1.15, P = .92). The risk of major bleeding was 4.6% in the aspirin group vs 3.8% in the placebo group (HR 1.23, 95% CI 1.01–1.49, P = .04).1

George et al,14 in a prospective observational study in a single tertiary care center, found that fewer patients with myocardial injury in noncardiac surgery died if they took aspirin or clopidogrel postoperatively. Conversely, lack of antithrombotic therapy was an independent predictor of death (P < .001). The mortality rate in patients with myocardial injury who were on antithrombotic therapy postoperatively was 6.7%, compared with 12.1% in those without postoperative antithrombotic therapy (estimated number needed to treat, 19).14

 

 

PATIENTS WITH CORONARY STENTS UNDERGOING NONCARDIAC SURGERY

Percutaneous coronary intervention (PCI) accounts for 3.6% of all operating-room procedures in the United States,15 and 20% to 35% of patients who undergo PCI undergo noncardiac surgery within 2 years of stent implantation.16,17

Antiplatelet therapy is discontinued in about 20% of patients with previous PCI who undergo noncardiac surgery.18

Observational data have shown that stopping antiplatelet therapy in patients with previous PCI with stent placement who undergo noncardiac surgery is the single most important predictor of stent thrombosis and death.19–21 The risk increases if the interval between stent implantation and surgery is shorter, especially within 180 days.16,17 Patients who have stent thrombosis are at significantly higher risk of death.

Graham et al4 conducted a subgroup analysis of the POISE 2 trial comparing aspirin and placebo in 470 patients who had undergone PCI (427 had stent placement, and the rest had angioplasty or an unspecified type of PCI); 234 patients received aspirin and 236 placebo. The median time from stent implantation to surgery was 5.3 years.

Of the patients in the aspirin arm, 14 (6%) had the primary outcome of death or nonfatal MI compared with 27 patients (11.5%) in the placebo arm (absolute risk reduction 5.5%, 95% CI 0.4%–10.5%). The result, which differed from that in the primary trial,1 was due to reduction in MI in the PCI subgroup on aspirin. PCI patients who were on aspirin did not have increased bleeding risk. This subgroup analysis, albeit small and limited, suggests that continuing low-dose aspirin in patients with previous PCI, irrespective of the type of stent or the time from stent implantations, minimizes the risk of perioperative MI.

GUIDELINES AND RECOMMENDATIONS

Routine perioperative use of aspirin increases the risk of bleeding without a reduction in ischemic events.1 Patients with prior PCI are at increased risk of acute stent thrombosis when antiplatelet medications are discontinued.20,21 Available data, although limited, support continuing low-dose aspirin without interruption in the perioperative period in PCI patients,4 as do the guidelines from the American College of Cardiology.5

Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.
Figure 1. Proposed perioperative management of aspirin and antiplatelet therapy in patients undergoing noncardiac surgery.

We propose a management algorithm for patients undergoing noncardiac surgery on antiplatelet therapy that takes into consideration whether the surgery is urgent, elective, or time-sensitive (Figure 1). It is imperative to involve the cardiologist, surgeon, anesthesiologist, and the patient in the decision-making process.

In the perioperative setting for patients undergoing noncardiac surgery:

  • Discontinue aspirin in patients without coronary heart disease, as bleeding risk outweighs benefit.
  • Consider aspirin in patients at high risk for a major adverse cardiac event if benefits outweigh risk.
  • Continue low-dose aspirin without interruption in patients with a coronary stent, irrespective of the type of stent.
  • If a patient has had PCI with stent placement but is not currently on aspirin, talk with the patient and the treating cardiologist to find out why, and initiate aspirin if no contraindications exist.
References
  1. Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370(16):1494–1503. doi:10.1056/NEJMoa1401105
  2. Fleisher LA, Fleischmann KE, Auerbach AD, et al; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2014; 64(22):e77–e137. doi:10.1016/j.jacc.2014.07.944
  3. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994; 308(6921):81–106. pmid:8298418
  4. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery. Ann Intern Med 2018; 168(4):237–244. doi:10.7326/M17-2341
  5. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 68(10):1082–1115. doi:10.1016/j.jacc.2016.03.513
  6. Albaladejo P, Marret E, Samama CM, et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart 2011; 97(19):1566–1572. doi:10.1136/hrt.2011.224519
  7. Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA 2012; 307(21):2295–2304. doi:10.1001/jama.2012.5502
  8. Botto F, Alonso-Coello P, Chan MT, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology 2014; 120(3):564–578. doi:10.1097/ALN.0000000000000113
  9. Gorka J, Polok K, Iwaniec T, et al. Altered preoperative coagulation and fibrinolysis are associated with myocardial injury after non-cardiac surgery. Br J Anaesth 2017; 118(5):713–719. doi:10.1093/bja/aex081
  10. Rajagopalan S, Ford I, Bachoo P, et al. Platelet activation, myocardial ischemic events and postoperative non-response to aspirin in patients undergoing major vascular surgery. J Thromb Haemost 2007; 5(10):2028–2035. doi:10.1111/j.1538-7836.2007.02694.x
  11. Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004; 93(1):9–20. doi:10.1093/bja/aeh147
  12. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ 2005; 173(6):627–634. doi:10.1503/cmaj.050011
  13. Antithrombotic Trialists’ (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373(9678):1849–1860. doi:10.1016/S0140-6736(09)60503-1
  14. George R, Menon VP, Edathadathil F, et al. Myocardial injury after noncardiac surgery—incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre. Medicine (Baltimore) 2018; 97(19):e0402. doi:10.1097/MD.0000000000010402
  15. Weiss AJ, Elixhauser A, Andrews RM; Healthcare Cost and Utilization Project (HCUP). Characteristics of operating room procedures in US hospitals, 2011: statistical brief #170. https://hcup-us.ahrq.gov/reports/statbriefs/sb170-Operating-Room-Procedures-United-States-2011.jsp. Accessed May 3, 2019.
  16. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013; 310(14):1462–1472. doi:10.1001/jama.2013.278787
  17. Wijeysundera DN, Wijeysundera HC, Yun L, et al. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation 2012; 126(11):1355–1362. doi:10.1161/CIRCULATIONAHA.112.102715
  18. Rossini R, Capodanno D, Lettieri C, et al. Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011; 107(2):186–194. doi:10.1016/j.amjcard.2010.08.067
  19. Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009; 119(12):1634–1642. doi:10.1161/CIRCULATIONAHA.108.813667
  20. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17):2126–2130. doi:10.1001/jama.293.17.2126
  21. Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006; 98(3):352–356. doi:10.1016/j.amjcard.2006.02.039
References
  1. Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370(16):1494–1503. doi:10.1056/NEJMoa1401105
  2. Fleisher LA, Fleischmann KE, Auerbach AD, et al; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2014; 64(22):e77–e137. doi:10.1016/j.jacc.2014.07.944
  3. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994; 308(6921):81–106. pmid:8298418
  4. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery. Ann Intern Med 2018; 168(4):237–244. doi:10.7326/M17-2341
  5. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 68(10):1082–1115. doi:10.1016/j.jacc.2016.03.513
  6. Albaladejo P, Marret E, Samama CM, et al. Non-cardiac surgery in patients with coronary stents: the RECO study. Heart 2011; 97(19):1566–1572. doi:10.1136/hrt.2011.224519
  7. Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA 2012; 307(21):2295–2304. doi:10.1001/jama.2012.5502
  8. Botto F, Alonso-Coello P, Chan MT, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology 2014; 120(3):564–578. doi:10.1097/ALN.0000000000000113
  9. Gorka J, Polok K, Iwaniec T, et al. Altered preoperative coagulation and fibrinolysis are associated with myocardial injury after non-cardiac surgery. Br J Anaesth 2017; 118(5):713–719. doi:10.1093/bja/aex081
  10. Rajagopalan S, Ford I, Bachoo P, et al. Platelet activation, myocardial ischemic events and postoperative non-response to aspirin in patients undergoing major vascular surgery. J Thromb Haemost 2007; 5(10):2028–2035. doi:10.1111/j.1538-7836.2007.02694.x
  11. Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004; 93(1):9–20. doi:10.1093/bja/aeh147
  12. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ 2005; 173(6):627–634. doi:10.1503/cmaj.050011
  13. Antithrombotic Trialists’ (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373(9678):1849–1860. doi:10.1016/S0140-6736(09)60503-1
  14. George R, Menon VP, Edathadathil F, et al. Myocardial injury after noncardiac surgery—incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre. Medicine (Baltimore) 2018; 97(19):e0402. doi:10.1097/MD.0000000000010402
  15. Weiss AJ, Elixhauser A, Andrews RM; Healthcare Cost and Utilization Project (HCUP). Characteristics of operating room procedures in US hospitals, 2011: statistical brief #170. https://hcup-us.ahrq.gov/reports/statbriefs/sb170-Operating-Room-Procedures-United-States-2011.jsp. Accessed May 3, 2019.
  16. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013; 310(14):1462–1472. doi:10.1001/jama.2013.278787
  17. Wijeysundera DN, Wijeysundera HC, Yun L, et al. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation 2012; 126(11):1355–1362. doi:10.1161/CIRCULATIONAHA.112.102715
  18. Rossini R, Capodanno D, Lettieri C, et al. Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011; 107(2):186–194. doi:10.1016/j.amjcard.2010.08.067
  19. Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009; 119(12):1634–1642. doi:10.1161/CIRCULATIONAHA.108.813667
  20. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17):2126–2130. doi:10.1001/jama.293.17.2126
  21. Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006; 98(3):352–356. doi:10.1016/j.amjcard.2006.02.039
Issue
Cleveland Clinic Journal of Medicine - 86(8)
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Cleveland Clinic Journal of Medicine - 86(8)
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518-521
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518-521
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Cleveland Clinic Journal of Medicine
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Cleveland Clinic Journal of Medicine
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Should we stop aspirin before noncardiac surgery?
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Should we stop aspirin before noncardiac surgery?
Legacy Keywords
aspirin, surgery, perioperative medication, prevention, stent thrombosis, VISION study, POISE study, myocardial injury after noncardiac surgery, MINS, bleeding, percutaneous coronary intervention, antiplatelet therapy, Anbazhagan Prabhakaran, Christopher Whinney
Legacy Keywords
aspirin, surgery, perioperative medication, prevention, stent thrombosis, VISION study, POISE study, myocardial injury after noncardiac surgery, MINS, bleeding, percutaneous coronary intervention, antiplatelet therapy, Anbazhagan Prabhakaran, Christopher Whinney
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