The role of aspirin for primary prevention of cardiovascular events in the elderly –

insights from the ASPREE TrialGeorge Marek MS4

Geriatrics EBM Presentation

Acetylsalicylic Acid• Irreversible Acetylation of COX1 at low concentration –COX2 at

higher doses

• Inhibits Platelet activation/aggregation• Reduced production of Thromboxane A2

• Complex Modulation of Systemic Inflammatory Mileau [1]

Research Question

- Is there sufficient Evidence to support aspirin use for primary

prophylaxis of MI in the elderly?

Literature Search Strategy

Search Criteria NCBI Pubmed DatabaseUSPSTF Guidelines

Search Terms (Aspirin) AND Geriatric AND aged[MeSH] – 196

Studies Via Pubmed

13 Systematic Review Articles with META

Analysis

General Primary PreventionReduced MI but No clear role in prevention of Stroke or CVD mortality [2]

USPSTF [3]

Subgroup Analyses suggest CVD benefits in Elderly

Several Studies offer post hoc and pre-specified subgroup analysis that suggests benefits of aspirin are greatest in older populations [4-6]

E.g. Woman’s Health Trial – Women 65+ are only subgroup with reduced CV events [4]

Not all studies show a statistically significant relationship, cutoffs are inconsistent and these studies are not designed to interrogate elderly populations specifically.

ASPREE Trial [7-9]

• Randomized Multi-center placebo controlled Trial With Multi Year Follow-up• Patients >/= 65 yo• 19k participants• Well randomized, adherence assessed pre-enrollment• Includes patients with medical comorbidity but not overt disease• Followed Patients until Death/Disability Median 4.7 yrs• Relatively low previous aspirin useers on enrollment so cannot address benefits/risks of long term therapy .

No change in composite endpoints

Increased risk of serious hemorrhage

No Differences in Cardiovascular Events

Summary

Aspirin has a beneficial profile for reducing nonfatal MI but not all cause or CV mortality

in general

Primary prophylaxis is not likely to result in decreased

cardiovascular mortality, or all cause mortality/disability

Aspirin use is significantly associated with serious

hemorrhage

Conclusions• Starting aspirin in an elderly individual without overt cardiovascular disease is potentially

inappropriate• Whether or not to continue aspirin for primary prophylaxis after long term use for primary

prophylaxis is unclear and should involve shared decision making and appropriate clinical judgement.

Questions?

References1. Modes of action of aspirin-like drugs.Abramson S, Korchak H, Ludewig R, Edelson H, Haines K, Levin RI, Herman R, Rider L, Kimmel S, Weissmann G.Proc Natl Acad Sci U S A. 1985 Nov;82(21):7227-31.PMID:29977782. Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.Guirguis-Blake JM, Evans CV, Senger CA, O'Connor EA, Whitlock EP.Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113. Epub 2016 Apr 12. Review.PMID:27064410

3. Final Recommendation Statement: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. U.S. Preventive Services Task Force. September 2017.https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer

4. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE.N Engl J Med. 2005 Mar 31;352(13):1293-304. Epub 2005 Mar 7.PMID:157531145. Final report on the aspirin component of the ongoing Physicians' Health Study.Steering Committee of the Physicians' Health Study Research Group.N Engl J Med. 1989 Jul 20;321(3):129-35.PMID:2664509

References (continued)6. Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment.Kjeldsen SE, Kolloch RE, Leonetti G, Mallion JM, Zanchetti A, Elmfeldt D, Warnold I, Hansson L.J Hypertens. 2000 May;18(5):629-42.7. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, AbhayaratnaWP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group.N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1803955. [Epub ahead of print]PMID:302215958. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radziszewska B, Jelinek M, Malik M, Eaton CB, Brauer D, Cloud G, Wood EM, Mahady SE, Satterfield S, Grimm R, Murray AM; ASPREEInvestigator Group.N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1805819. [Epub ahead of print]PMID:302215979. Effect of Aspirin on Disability-free Survival in the Healthy Elderly.McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Ryan J, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group.N Engl J Med. 2018 Sep 16. doi: 10.1056/NEJMoa1800722. [Epub ahead of print]PMID:30221596