A Comprehensive Update on Aspirin Management During Noncardiac Surgery

Neal S. Gerstein, MD, FASE; Cory L. Albrechtsen, BS; Nestor Mercado, MD, PhD; Joaquin E. Cigarroa, MD; Peter M. Schulman, MD

Disclosures

Anesth Analg. 2020;131(4):1111-1123. 

In This Article

Aspirin use in CV Disease

Aspirin irreversibly acetylates both cyclooxygenase-1 and cyclooxygenase-2.[19] At low doses (75–100 mg daily) typically used for the management of CV disease, the impact on cyclooxygenase-1 predominates, which produces its antithrombotic effects by inhibiting the production of thromboxane A2 (TXA-2) and attenuating platelet aggregation.[1,20]

Aspirin in the Primary Prevention of CV Disease

Before 2018, aspirin was recommended for men >50 years and women >60 years without established CV disease, provided they had certain CV risk factors (ie, diabetes with certain concomitant risk factors) and a ≥10% risk of developing CV disease within a 10-year period.[1,22–24] The cutoff of ≥10% risk of CV disease within 10 years was established to balance the associated increased risk of bleeding with aspirin (primarily gastrointestinal [GI]; rarely, hemorrhagic stroke) against its salutary CV effects. However, beginning in 2018, the results of 3 randomized prospective trials and 2 subsequent large meta-analyses were published challenging prior recommendations.[25–27]

The Aspirin in Reducing Events in the Elderly (ASPREE)[25] trial compared 100 mg of aspirin per day (n = 9525) to placebo (n = 9589) in a healthy elderly population without CV disease over a median follow-up of 4.7 years. No difference was found between the groups in the composite primary end point of death, dementia, or persistent physical disability (hazard ratio [HR] = 1.01, 95% confidence interval [CI], 0.92–1.11; P = .79). Furthermore, while aspirin did not yield a CV benefit, its use resulted in a higher risk of major bleeding (HR = 1.39, 95% CI, 1.18–1.62; P < .001).[25]

The A Study of Cardiovascular Events iN Diabetes (ASCEND)[26] trial randomized 15,480 patients over 40 years old with diabetes and without CV disease to aspirin 100 mg/d or placebo. During a mean follow-up of 7.4 years, aspirin use was associated with a 12% reduction in the rate of serious vascular events (composite of nonfatal MI, nonfatal stroke or transient ischemic attack [TIA], or death from any vascular cause excluding intracranial hemorrhage; rate ratio = 0.88, 95% CI, 0.79–0.97; P = .01). However, the rate of major bleeding (mainly GI and other extracranial events) was 29% greater in the aspirin group (rate ratio = 1.29, 95% CI, 1.09–1.52; P = .003).[26] All-cause mortality between the 2 groups was similar (rate ratio = 0.94, 95% CI, 0.85–1.04).

The use of Aspirin to Reduce Risk of Initial Vascular Events in patients at moderate risk of CV disease (ARRIVE)[27] trial randomized 12,546 men ≥55 years and women ≥60 years without diabetes or CV disease but at a 10-year CAD risk of 10%–20% to receive 100 mg of daily aspirin or placebo. During a median follow-up of 5 years, there was no difference in the primary efficacy end point (composite of time to first MI, stroke, CV death, unstable angina, or TIA) between the groups (HR = 0.96, 95% CI, 0.81–1.13; P = .60). However, nonfatal GI bleeding was 2-fold higher with aspirin (HR = 2.11, 95% CI, 1.36–3.28; P = .0007).[27] There was no difference in the rate of fatal bleeding or all-cause mortality (HR = 0.99, 95% CI, 0.8–1.24; P = .95).

In 2019, 2 meta-analyses examined the use of aspirin in primary prevention and included the 3 aforementioned randomized controlled trials (RCTs). The first analyzed 11 trials with 157,248 subjects and found no difference in the incidence of all-cause mortality with aspirin, including in those with diabetes or with a >7.5% 10-year risk for CV disease. Moreover, aspirin was found to be associated with an increased incidence of major bleeding.[4] The second analyzed 13 trials with 164,225 subjects and found that aspirin use was associated with a significant reduction in a composite CV outcome (mortality, nonfatal MI, and nonfatal stroke; HR = 0.89, 95% CI, 0.84–0.94), but also found an increased risk of major bleeding events (HR = 1.43, 95% CI, 1.30–1.56).[5]

The results of these studies led the American College of Cardiology (ACC)/American Heart Association (AHA) to publish their latest Guideline on the Primary Prevention of Cardiovascular Disease in 2019 (Table 1),[28] in which the use of aspirin in select high-risk patients was downgraded from class I to IIb.[28] Furthermore, the guideline now recommends against prophylactic aspirin use in patients >70 years or in anyone at increased risk of bleeding regardless of age (class III).

Aspirin for Secondary Prevention of CV Disease

Low-dose aspirin therapy provides significant net clinical benefit for patients at risk for subsequent events secondary to existing CV disease (CAD, CVD, and PAD). Current guidelines for the secondary prevention of CV disease recommend antiplatelet regimens based on CV disease type, clinical context (ie, with or without recent acute coronary syndrome [ACS]), and chronicity as outlined in Table 2, Table 3 and Table 4.

The benefit of aspirin in secondary prevention was conclusively demonstrated by the 2002 Antithrombotic Trialists' Collaboration (ATC) meta-analysis.[30] This study evaluated 16 randomized trials in 71,912 high-risk patients with established CV disease and found that antiplatelet therapy (principally aspirin) reduced all-cause mortality, nonfatal MI, and nonfatal stroke in these high-risk patients to a more significant degree than it increased nonfatal extracranial bleeding.[30] The most current ACC/AHA guideline on the management of CAD recommends lifelong aspirin in nearly all pertinent clinical scenarios.[29]

Similarly, the most recent AHA/American Stroke Association guideline on secondary stroke prevention gives lifelong antiplatelet therapy (aspirin, clopidogrel, or aspirin/dipyridamole combination) a class I recommendation in patients with a history of ischemic stroke or TIA.[31] In a metaregression analysis of 11 placebo-controlled trials examining the use of aspirin for secondary stroke prevention, aspirin was associated with a relative risk reduction of 15% (95% CI, 6–23).[32] The ATC meta-analysis also demonstrated that antiplatelet therapy led to a relative risk reduction from recurrent ischemic stroke of approximately 22% with a number needed to treat of 28 over 2.5 years.[30]

Finally, for patients with established PAD, the ATC meta-analysis also demonstrated a 23% (P = .004) reduction in recurrent serious vascular events (MI, stroke, and vascular death) with the use of an antiplatelet agent.[30] The current AHA/ACC guideline considers daily aspirin or clopidogrel a class I recommendation in patients with symptomatic PAD (ie, claudication or prior lower extremity revascularization) to reduce the risk of MI, stroke, and vascular death.[33]

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