Diabetes and aspirin

Diabetes and aspirin

By Donna Itzstein

Diabetes Queensland Pharmacist

 The guidelines regarding low-dose aspirin in diabetes have changed over time.

Previously, it was thought aspirin was appropriate for anyone at risk of cardiovascular disease (CVD).  This article discusses the current guidelines around diabetes and aspirin. Studies also reveal some surprising prescribing points for you to consider.

 

Aspirin

 

Primary prevention

Currently, the Australian Therapeutic guidelines and General Practice Management of Type 2 Diabetes guidelines state:

Aspirin and other antiplatelet drugs are not routinely recommended for the primary prevention of cardiovascular disease. (1) (2)

The results for aspirin in primary prevention of CVD remain mixed. The change in Australian and European guidelines reflect the results of the ASCEND study.

The ASCEND study 2005-2011 (3)AspirinPlacebo
15,480 people>40 years of age with diabetes mellitus without evident CVDrandomized to 100 mg of aspirin vs placebo dailymean follow-up of 7.4 years 8.5% 9.6%serious vascular events
4.1%3.2%major bleeding events

 

The conclusion was although aspirin prevented serious vascular events in people living with diabetes and with no previous CVD, the benefits were offset by the risk of major bleeding.

American guidelines recommend the use of low-dose aspirin for people with diabetes who are:

  • At an increased risk of CVD but have no previous history and
  • not at an increased risk for bleeding and are,
  • men >50 years or women >60 years.

Established atherosclerotic cardiovascular disease

Australian Therapeutic guidelines

Regardless of the initial antiplatelet regimen, most patients with atherosclerotic CVD benefit from long-term therapy with aspirin 100 to 150 mg or clopidogrel 75 mg orally, daily. Do not use dual antiplatelet therapy (i.e. aspirin plus clopidogrel) in patients with stable peripheral arterial disease. It has no advantage over aspirin alone and is associated with increased bleeding. (1)

During the 12 months following an acute coronary syndrome, dual therapy is recommended. Generally once an anticoagulant therapy is commenced, antiplatelet therapy is ceased until the anticoagulant is withdrawn. Dual therapy with an anticoagulant and antiplatelet increases the risk of major bleeding significantly. In certain high-risk patients (e.g. recent coronary stenting), it may be appropriate to continue the antiplatelet drug (in addition to an anticoagulant drug) with specialist advice.

Intermittent claudication (leg cramps) such as found in peripheral vascular disease

The recommendation is aspirin 100 to 150 mg or clopidogrel 75 mg orally, daily. (4) Rivaroxaban is another option, which may soon become available in Australia under the Pharmaceutical Benefit Scheme.

Prescribing points

  • If using enteric-coated (EC) aspirin preparations aspirin is released quickly and almost completely when the PH is higher. For this reason, optimal dosing of EC aspirin is best taken before a meal or before sleep. This dosing reduced the frequency of adverse gastric reactions. (5)
  • It is debatable whether EC aspirin decreases the frequency of adverse gastric reactions, and may in fact lead to suboptimal results compared to aspirin immediate release. In fact, the cause of gastric reactions such as bleeding is thought to be mainly as a result of platelet inhibition rather than local irritation. Immediate release aspirin has a sufficient body of evidence supporting its role in the treatment of cardiovascular disease. (6)
  •  Studies show:
    • Twice daily administration of low dose aspirin was superior to once daily dosing,
    • Increased body weight is associated with lower aspirin responsiveness regardless of diabetes. (7)
  • Taking Aspirin with Non-steroidal anti-inflammatory medications such as Ibuprofen will reduce antiplatelet action and may increase gastrointestinal adverse reactions. Occasional use is acceptable due to the long-lasting effects of aspirin on platelets. Paracetamol and Celecoxib do not interfere.
  • Food does not affect the amount absorbed with low dose aspirin. The absorption of aspirin is delayed by food. (8)
  • Any alcohol intake will increase rates of gastrointestinal bleeding.

 

Bibliography

  1. Therapeutic Guidelines LtdeTG January 2019 edition. s.l. : Therapeutic Guidelines Ltd, January 2019.
  2. The Royal College of General Practioners and Diabetes Australia. General Practice Management of type 2 diabetes 2016-18. [Online] April 2019. [Cited: 2019.] https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/5d3298b2-abf3-487e-9d5e-0558566fc242.pdf.
  3. Effects of aspirin for primary prevention in persons with diabetes mellitus: the ASCEND Study Collaborative Group. Bowman, L, et al. 1, January 1st, 2019, Journal of Vascular Surgery, Vol. 69, p. 305.
  4. Antiplatelet agents for intermittent claudication. Cochrane Database of Systematic Reviews.Wong PF, Chong LY, Mikhailidis DP, Robless P, Stansby G. 11, 2011.
  5. Relationship between adverse gastric reactions and the timing of enteric-coated aspirin administration. Wejun, G, et al. 2, Auckland : s.n., February 2017, Clinical drug investigation, Vol. 37.
  6. Enteric-coated aspirin in cardiac patients: Is it less effective than aspirin. R, Jirmar and P, Widimsy. 2, 2018, Vol. 60.
  7. Type 2 diabetes, Obesity and aspirin responsiveness. C, Patrono and B, Rocca. 6, 2017, Journal of American College of Cardiology, Vol. 69.
  8. Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDS- a systemic review. A, Moore R, et al. 3, 2015, British journal of clinical pharmacology, Vol. 80.

 

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