Aspirin Topic Review

Aspirin (acetylsalicylic acid) is a versatile drug from the salicylate class.

Salicylates are derived from the bark of willow (the genus Salix, which gives the drug class its name) and several other plants. They have been utilized in folk remedies for thousands of years before the advent of scientific medicine. Aspirin itself has been in use since the early 20th century, primarily for its analgesic and anti-inflammatory effects. [Arif H, et al. StatPearls. 2020;1a-b] However, low-dose aspirin also has an antithrombotic effect, which has made it a mainstay therapy for the secondary prevention of cardiovascular disease. [Byrne RA, et al. Lancet. 2020;1a;2a]

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Aspirin is a potent and irreversible inhibitor of the enzymes cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2). These enzymes catalyze critical steps in the biosynthetic pathway of prostaglandins and of thromboxane A2 (TXA2), a potent inducer of platelet aggregation and thrombosis. [Arif H, et al. StatPearls. 2020;1c; Patrono C, et al. Nat Rev Cardiol. 2019;2a-b] Impairment of TXA2 function explains the most concerning risk of chronic low-dose aspirin use — that of gastrointestinal bleeding — because TXA2 is a key effector of the platelet response in primary hemostasis. [Patrono C, et al. Nat Rev Cardiol. 2019;2b] The irreversible antiplatelet effects of a single dose of aspirin last approximately 7 days, until platelet turnover supplies a sufficient number of unexposed, functional platelets for normal hemostasis.

Inhibition of COX enzymes also shuttles arachidonic acid into alternative pathways that produce lipoxins, most of which have anti-inflammatory effects. [Arif H, et al. StatPearls. 2020;1c]

Indications: Secondary Prevention

Numerous clinical trials have demonstrated a favorable risk-benefit ratio of low-dose aspirin use for the secondary prevention of cardiovascular events in patients with clinically established ASCVD, particularly coronary artery disease (CAD; now also called chronic coronary syndrome [CCS]). [Byrne RA, et al. Lancet. 2020;1a; Jacobsen AP, et al. Circulation. 2020;2a]

The 2011 American College of Cardiology/American Heart Association guidelines on the secondary prevention of ASCVD provide the following recommendation on the use of aspirin:

• Aspirin 75-162 mg daily is recommended in all patients with coronary artery disease unless contraindicated [Smith SC Jr, et al. Circulation. 2011;3a]

Indications: Primary Prevention

In contrast to the established favorable risk-benefit ratio for the secondary prevention of ASCVD, the use of aspirin for primary prevention of ASCVD is controversial. Many experts feel that the demonstrated preventive benefits do not outweigh the risk for bleeding complications (ie, no net benefit). [Byrne RA, et al. Lancet. 2020;1a] One of the key “take-home” messages from the 2019 ACC/AHA guidelines on the primary prevention of ASCVD states that “Aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit”. [Arnett DK, et al. Circulation. 2019;3a] The guidelines make the following three recommendations: [Arnett DK, et al. Circulation . 2019;28a]

• Low-dose aspirin (75-100 mg orally daily) might be considered (Class IIb recommendation) for the primary prevention of ASCVD among select adults 40 to 70 years of age who are at higher ASCVD risk but not at increased bleeding risk.
• Low-dose aspirin (75-100 mg orally daily) should not be administered (Class III: Harm) on a routine basis for the primary prevention of ASCVD among adults older than 70 years of age.
• Low-dose aspirin (75-100 mg orally daily) should not be administered (Class III: Harm) for the primary prevention of ASCVD among adults of any age who are at increased risk for bleeding.

Indications: Therapeutic

Aspirin is also used therapeutically during and following an acute coronary syndrome and percutaneous coronary intervention (PCI). The 2021 ACC/AHA/Society for Cardiovascular Angiography and Interventions  guidelines for coronary artery revascularization recommend (Class I) a loading dose of aspirin (162-325 mg orally) followed by daily dosing (75-100 mg) to reduce ischemic events in patients undergoing PCI. [Lawton JS, et al. J Am Coll Cardiol. 2021;47a;49a] The guidelines also recommend that patients undergoing coronary artery bypass graft (CABG) surgery already on daily aspirin should (Class I recommendation) continue taking aspirin until the time of surgery. However, initiating aspirin in the immediate pre-operative period is not recommended (Class III: No benefit). [Lawton JS, et al. J Am Coll Cardiol. 2021;59a. ] Following CABG, aspirin (100-325 mg daily) “should be initiated within 6 hours postoperatively and then continued indefinitely to reduce the occurrence of saphenous vein graft closure and adverse cardiovascular events.” [Lawton JS, et al. J Am Coll Cardiol. 2021;63a]

References:

• Arnett DK, et al. Circulation. 2019;doi:10.1161/CIR.0000000000000678.
• Arif H, et al. Updated July 15, 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
• Byrne RA, et al. Lancet. 2020;doi:10.1016/S0140-6736(20)30799-6.
• Jacobsen AP, et al. Circulation. 2020;doi:10.1161/CIRCULATIONAHA.120.045695.
• Lawton JS, et al. K Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2021.09.006.
• Patrono C, et al. Nat Rev Cardiol. 2019;doi:10.1038/s41569-019-0225-y.
• Smith SC Jr, et al. Circulation. 2011;doi:10.1161/cir.0b013e318235eb4d.