By Professor John McNeil*, Monash University
The efficacy of low-dose aspirin for the secondary prevention of cardiovascular disease has been established in a series of randomized clinical trials dating from the early 1970s. Subsequent primary prevention trials suggested similar efficacy for individuals free of cardiovascular disease. As a result low-dose aspirin has become widely prescribed for otherwise healthy individuals perceived to be at high risk of heart disease. Data from the US have suggested that up to 40% of eligible individuals take daily aspirin for this purpose.
Since about 2000 additional primary prevention trials with aspirin have been published where the results have been less consistent, leading to the establishment of three more definitive trials, all three of which were published in the latter half of 2018.
The ASCEND trial focussed on aspirin for primary prevention in diabetics, the ARRIVE trial in patients at moderately high CVD risk, and the ASPREE trial on the elderly.
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The results were uniformly unimpressive, with higher rates of bleeding that appeared to negate any cardiovascular benefit. The outcome in the ASPREE trial was disability-free survival, a composite of survival free of disability or dementia which was also unaffected by aspirin. A higher mortality rate amongst the elderly participants in that trial , due mainly to an increased mortality from cancer , was unexpected and may be specific to an elderly population.
Given the new evidence, the AHA/ACC guidelines for the use of aspirin were recently revised and the recommendation for aspirin use in individuals aged 70 years and above, was altered from ‘efficacy unknown’ to ‘low-dose aspirin (75-100 mg orally daily) should not be administered on a routine basis for the primary prevention of ASCVD among adults >70 years of age.
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Conclusions
Recent clinical trials have raised doubts about the value of prescribing low-dose aspirin for primary prevention of CVD, especially amongst individuals aged 70 years and older.
Professor John McNeil
MBBS (Adelaide), MSc (London), PhD (Melbourne), FRACP, FAFPHM
Head of Department of Epidemiology and Preventive Medicine
Head of School of Public Health and Preventive Medicine
Monash University, Melbourne. Australia
References
- ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 ;379(16):1529-1539
- Gaziano JM1, Brotons C2, Coppolecchia R3, Cricelli C4, Darius H5, Gorelick PB6, Howard G7, Pearson TA8, Rothwell PM9, Ruilope LM10, Tendera M11, Tognoni G12; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10152):1036-1046.
- 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; ASPREE Investigator Group. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med. 2018 379:1509-1518.
- Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019 Mar 17:CIR0000000000000678. doi: 10.1161/CIR.0000000000000678. [Epub ahead of print]