Aspirine®

Monopgraph

Therapeutic action

Aspirin®is an irreversible inhibitor of prostaglandin formation. It has anti-inflammatory, analgesic, antipyretic and anticoagulant effect. Because of its anticoagulant effect it is used for theprevention of thromboembolic events.

Metabolism

Acetylsalicilic is eliminated mainly through conjugation with glycine and to a lesser extent with glucuronic acid. Even though its half-life is somewhat short (8-12 days), given that the inhibition it produces is irreversible, his anticoagulant effects remain for the whole life of the platelet.

Other factors to be considered

Acetylsalicilic acid, an OTC drug, is very used as an analgesic as a self-medication. On the other hand, the use of acetylsalicilic acid , as well as other NSAIDs, increases the risk of gastrointestinal bleeding due to the inhibition of the prostaglandine synthesis in the gastrointestinal mucose. In secondary prevention (prevention of new episodes in patients with evident cardiovascular risk), acetylsalicilic acid confers a benefit that exceeds the risk of gastrointestinal bleeding, but in primary prevention (prevention of episodes without a previous pathology or suspitions of risk) the benefit and the risk have the same order of magnitude, or a significantly higher benefit for this therapy can not be found.  Therefore it is not indicated to use aspirin for the primary prevention of cardiovascular risk.However, two genetic polymorphisms in theLPAgene, rs3798220  and rs10455872, have been associated with an increased risk for cardiovascular disease(risk  x1.8 for one variant, risk x4 for two, according to Clarke R. et al 2009), that revert during a treatment with acetylsalicilic acid to the level of the general population. About 15% of the caucasic population carries at least one risk allele. The genotype for theLPApolymorphisms can be used as a biomarker to identify those people for a therapy with acetylsalicilic acid would be adequate for primary prevention of cardiovascular eventsdue to a favourable benefit/risk ratio. Furthermore, the use of genotyping to guide the preventive use of acetylsalicilic acid would be cost-efective according to a study from Shiffman D. et al (2012).The coadministration of some NSAIDs, such as ibuprofen or dipyrone can reduce the preventive effect of acetylsalicilic acid. The reason is that both these NSAIDs and aspirin compete for inhibiting COX-1, but unlike aspirine, which is an irreversible inhibitor, the binding of ibuprofen or dipyrone is reversible, and therefore their effects do not last for a long time.

Conclusions

Dado que el uso de aspirina no está exento de riesgos su uso no debe generalizarse en forma de prevención primaria. Sólo debería usarse aspirina preventivamente en ausencia de signos clínicos si hay un indicio de riesgo aumentado.En pacientes portadores de alelos de riesgo en los marcadores rs3798220 y el rs10455872 del gen LPA el uso de aspirina está indicadoy reduce el riesgo de eventos cardiovasculares hasta equipararlo al de la población general. En el resto de pacientes, el riesgo de efectos adversos excede el beneficio potencial.

Bibliography

• Seshasai S.R. et al. (2012). Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 172(3):209-16.
• Shiffman D. et al. (2012). Cost-effectiveness model of use of genetic testing as an aid in assessing the likely benefit of aspirin therapy for primary prevention of cardiovascular disease. Clin Ther. 34(6):1387-94.
• Berger J.S. et al. (2011). Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials. Am Heart J. 162(1):115-24.e2.
• Garcia Rodriguez L.A. et al. (2011). Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation; 123:1108-1115.
• Li Y. et al. (2011). Genetic variants in the apolipoprotein(a) gene and coronary heart disease. Circ Cardiovasc Genet. 4(5):565-73.
• Baigent C. et al. (2009). Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet; 373(9678):1849-60.
• Chasman DI, et al. (2009).Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis; 203: 371–376.
• Clarke R. et al. (2009). Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med; 361(26):2518-28.
• Wolff T, Miller T, Ko S. (2009). Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 150(6):405-10.
• Hernández-Díaz S, García Rodríguez LA. (2006). Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med. 4:22.
• Ridker P.M. et al. (2005). A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. (2005); 352(13):1293-304.

Marc Cendrós BertranLicenciado en BiologíaMáster en Asesoramiento Genético

Last modified: Sep 6, 2017 @ 09:59 am