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Clinical research study
Prevalence of High On-treatment Platelet Reactivity in Diabetic Patients Treated with Aspirin

https://doi.org/10.1016/j.amjmed.2013.09.019Get rights and content

Abstract

Background

Randomized controlled trials have shown that ≤100 mg aspirin daily is not effective for primary prevention of cardiovascular events in diabetes; however, clinical and pharmacologic evidence suggests these patients need >100 mg for adequate antiplatelet activity. Although high on-treatment platelet reactivity (HTPR) could explain the lack of benefit, prevalence of HTPR in diabetes is not known. This systematic review examined the relationship between daily aspirin dose and prevalence of HTPR in patients with diabetes.

Methods

Three electronic databases were searched until May 2013 using database-appropriate terms for aspirin, resistance, and diabetes. Studies were included if prevalence of HTPR was reported according to daily dose and diabetes status. Patients were stratified by daily aspirin dose and the weighted mean prevalence across studies was calculated. Where appropriate, pooled relative risks (RR) were calculated using a random-effects model.

Results

Data were available from 31 studies that enrolled 2147 diabetic patients. Overall, prevalence of HTPR was 21.9% (95% confidence interval [CI], 15.2%-28.5%) in diabetic patients and 15.8% (95% CI, 11.4%-20.3%) in nondiabetic patients (pooled RR 1.36; 95% CI, 1.08-1.71; I2 56%). Prevalence appeared to be dose related, with 398 (23.6%) of 1689 diabetic patients using ≤100 mg daily having HTPR compared with 64 (12.3%) of 518 diabetic patients using 101-325 mg daily (pooled RR 1.70; 95% CI, 1.07-2.72; I2 0%).

Conclusions

Although these observations should be verified in a clinical trial, the possibility that 1 in 4 patients have HTPR with doses commonly used in diabetes could have significant implications on overall effectiveness of aspirin.

Section snippets

Literature Search

Studies published in English were eligible for inclusion if they examined platelet response to aspirin in patients with diabetes. MEDLINE, Embase, and International Pharmaceutical Abstracts were searched from inception through May 31, 2013. Each database was searched using database-appropriate terms for aspirin, resistance, and diabetes or risk factor (Appendix). The electronic database search was supplemented by hand searching reference lists of included studies and review articles describing

Results

The search strategy identified 707 unique citations (Figure 1). After screening the titles and abstracts, 123 citations were considered potentially relevant and a copy of the full article was retrieved for further examination. The investigators disagreed on allocation of 13 (11%), and after review by a third investigator, we determined that 31 (25%) met all inclusion criteria.

Characteristics of the 3 randomized trials,7, 15, 16 8 cohort studies,17, 18, 19, 20, 21, 22, 23, 24 and 20

Discussion

This systematic review combined data from 31 studies with 2147 diabetic patients to examine the relationship between daily aspirin dose and prevalence of HTPR. Diabetic patients were 36% more likely to have HTPR compared with nondiabetic patients. Prevalence also varied by dose, with diabetic patients using the same doses tested in randomized controlled trials (≤100 mg daily) 70% more likely to have HTPR compared with diabetic patients using 101-325 mg daily.

Our observation that HTPR was

Conclusion

Although these observations should be verified in a properly designed randomized clinical trial, it is possible that 1 in 4 diabetic patients currently taking aspirin to prevent a cardiovascular event have high platelet reactivity. This HTPR could, in turn, have significant implications on the overall effectiveness of aspirin. Therefore, patients and clinicians may consider measuring platelet function and, if HTPR is present, either increase the aspirin dose to 162 or 325 mg daily or use an

Acknowledgment

We are very grateful for the additional information provided by authors of 6 studies included in this review (highlighted in the Table*). Mr Abdelmoneim and Ms Omran are supported by studentships through the Alberta Diabetes Institute and the Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD) Strategic Training Program in Diabetic Research. Mr Abdelmoneim also is supported through the Drug Safety and Effectiveness Cross-Disciplinary Training Program.

An abstract of this study

References (51)

  • L. Macchi et al.

    Aspirin resistance in vitro and hypertension in stroke patients

    J Thromb Haemost

    (2004)
  • D.J. Angiolillo et al.

    Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention

    Am J Cardiol

    (2006)
  • D. Bennett et al.

    A pilot study of resistance to aspirin in stroke patients

    J Clin Neurosci

    (2008)
  • H.W. Cohen et al.

    Aspirin resistance associated with HbA1c and obesity in diabetic patients

    J Diabetes Complications

    (2008)
  • J.I. Seok et al.

    Can aspirin resistance be clinically predicted in stroke patients?

    Clin Neurol Neurosurg

    (2008)
  • L. Liu et al.

    Prevalence and risk factors for aspirin resistance in elderly patients with type 2 diabetes

    Int J Gerontol

    (2011)
  • A. Abaci et al.

    Effect of increasing doses of aspirin on platelet function as measured by PFA-100 in patients with diabetes

    Thromb Res

    (2005)
  • E.H. Law et al.

    Aspirin use rates in diabetes: a systematic review and cross-sectional study

    Can J Diabetes

    (2010)
  • K.A. Schwartz et al.

    Compliance as a critical consideration in patients who appear to be resistant to aspirin after healing of myocardial infarction

    Am J Cardiol

    (2005)
  • V.L. Serebruany et al.

    Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials

    Am J Cardiol

    (2005)

  • Executive summary: standards of medical care in diabetes—2013

    Diabetes Care

    (2013)
  • J.A. Stone et al.

    Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada: vascular protection in people with diabetes

    Can J Diabetes

    (2013)
  • M. Sacco et al.

    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)
  • J. Belch 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)
  • H. Ogawa et al.

    Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial

    JAMA

    (2008)

    • Cited by (0)

    Funding: None.

    Conflict of Interest: None.

    Authorship: SHS: Study concept and design, data acquisition, statistical analysis and interpretation of data, drafting the manuscript and critical revision of manuscript; ASA: data acquisition, interpretation of data, and critical revision of manuscript; DO: data acquisition, interpretation of data, and critical revision of manuscript; TRF: data acquisition, interpretation of data, and critical revision of manuscript. SHS had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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