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Can Fam Physician. 2010 July; 56(7): 664.
PMCID: PMC2922803

Type 2 diabetes and ASA

G. Michael Allan, MD CCFP
Associate Professor in the Department of Family Medicine at the University of Alberta in Edmonton and the Medical Director of Toward Optimized Practice
Noah Ivers, MD CCFP
Family physician at Women’s College Hospital in Toronto, Ont

Clinical question

Should acetylsalicylic acid (ASA) be recommended for all patients who have type 2 diabetes but no history of cardiovascular disease (CVD)?

Evidence

Two recent randomized controlled trials of ASA in type 2 diabetics addressed this question.

  • The JPAD (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) study1 examined 2539 patients with type 2 diabetes taking low-dose ASA (81 to 100 mg) or nothing for a median of 4.4 years.
    • -CVD events were not significantly different:
      • —5.4% for those taking ASA versus 6.7% for those not taking ASA (P = .16).
    • -Bleeding events (hemorrhagic stroke and severe gastrointestinal bleeding) were not significantly different.
    • -In patients older than 65 years (prespecified subgroup), ASA reduced CVD events:
      • —6.3% for those taking ASA versus 9.2% for those not taking ASA (P = .047; number needed to treat = 35).
  • The POPADAD (Prevention of Progression of Arterial Disease and Diabetes) study2 followed 1276 patients with type 2 diabetes (with asymptomatic peripheral artery disease) taking low-dose ASA (100 mg) or placebo for a median of 6.7 years.
    • -CVD events were not significantly different:
      • —18.2% for those taking ASA versus 18.3% for those taking placebo (P = .86).
    • -Gastrointestinal bleeding events were not significantly different (P = .69).

Context

These findings are supported by the PPP (Primary Prevention Project) study of higher-risk patients without history of CVD.3

  • In those with diabetes (1031 patients), ASA did not result in a statistically significant difference in CVD events.
  • Those without diabetes (3753 patients) who had 1 or more risk factors for CVD had a statistically significant benefit with ASA (P = .03).

A recent meta-analysis combined JPAD1 and POPADAD2 with subgroups of patients with diabetes extracted from other studies and also found no overall advantage for ASA in primary prevention for those with type 2 diabetes.4

Canadian Diabetes Association guidelines5 correctly suggest that ASA is not necessary in all patients with diabetes but that it could be considered in “high-risk” groups.

  • Their definition of high-risk includes men 45 years or older, women 50 years or older, patients with microvascular or macrovascular disease, those with family history of CVD, those who have had diabetes for more than 15 years, or those with an extreme level of a single risk factor (eg, low-density lipoprotein > 5.0 mmol/L).
  • However, this high-risk group includes patients who did not benefit from ASA in the latest studies.13

High-quality evidence has not clearly identified which “high-risk” patients with diabetes will benefit from ASA (except perhaps those aged 65 or older).

Bottom line

According to current evidence, ASA should not be universally recommended for patients with type 2 diabetes who have no history of CVD.

Implementation

Prescribe ASA to patients with diabetes judiciously and alter flow sheets, checklists, or current standards of care accordingly. In 1 study,1 the patients with diabetes who benefited from ASA had a mean 10-year CVD risk of more than 20%. You can estimate risk periodically by linking to online6 calculators (or adding paper-based7 calculators) in patients’ charts. Patients’ estimated CVD risk can inform discussion regarding starting (or stopping) low-dose ASA.

Notes

Tools for Practice articles in Canadian Family Physician are adapted from articles published twice monthly on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician. Feedback is welcome and can be sent to ac.cpfc@ecitcarprofsloot. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

The opinions expressed in this Tools for Practice article are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

References

1. Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41. Erratum in: JAMA 2009;301(18):1882. [PubMed]
2. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, et al. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840. DOI: 10.1136/bmj.a1840. [PubMed]
3. Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care. 2003;26(12):3264–72. [PubMed]
4. De Berardis G, Sacco M, Strippoli GF, Pellegrini F, Graziano G, Tognoni G, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ. 2009;339:b4531. DOI: 10.1136/bmj.b4531. [PubMed]
5. Fitchett D, Kraw M. Vascular protection in people with diabetes. Can J Diabetes. 2008;32(Suppl 1):S102–6.
6. Payne R. University of Edinburgh Cardiovascular Risk Calculator [online tool] Edinburgh, UK: University of Edinburgh; 2010. Available from: http://cvrisk.mvm.ed.ac.uk/calculator/calc.asp. Accessed 2010 May 19.
7. National Prescribing Service . New Zealand Cardiovascular Risk Calculator [printable tool] Surry Hills, NSW: National Prescribing Service; 2004. Available from: www.qml.com.au/Files/CardioRiskCalc.pdf. Accessed 2010 May 19.

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada