Aspirin resistance and diabetes mellitus

Published on Jan 16, 2008in Diabetologia7.518
· DOI :10.1007/S00125-007-0898-3
Ramzi Ajjan34
Estimated H-index: 34
(University of Leeds),
Robert F. Storey90
Estimated H-index: 90
(University of Sheffield),
Peter J. Grant87
Estimated H-index: 87
(University of Leeds)
Sources
Abstract
Despite multiple interventions to reduce the risk of cardiovascular disease, the majority of people with diabetes develop macrovascular complications, and mortality following myocardial infarction remains unacceptably high [1]. Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease, although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [2]. In fact, there is little direct evidence supporting its efficacy in this group of patients. Instead, there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes. In a meta-analysis of 287 randomised trials, antiplatelet treatment (aspirin in most studies) reduced the risk of ischaemic events by 22%, but the risk reduction in the subgroup with diabetes was only 7%, which was not statistically significant [3]. This outcome was mirrored in the Primary Prevention Project trial, which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [4]. Despite this, there are no published studies specifically designed to evaluate the clinical efficacy of aspirin in individuals with diabetes, a surprising omission in the era of ‘evidencebased’ medicine. These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of aspirin in patients with diabetes compared with a nondiabetic population. Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk—a possibility that has led to the hotly debated concept of aspirin resistance [5, 6]. Unfortunately, aspirin resistance suffers from a lack of a standardised definition, although now generally thought of as either (1) reflecting clinical aspirin resistance (or perhaps, more accurately, treatment failure), characterised by the occurrence of a thrombotic episode despite treatment with aspirin; or (2) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin. Controversy remains as to the cause of biochemical aspirin resistance, its relevance to clinical outcomes, and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients. All of this highlights the urgent need to understand the mechanisms that underpin the interactions between diabetes and aspirin, to establish the role of aspirin in particular, and antiplatelet therapy in general, in the amelioration of cardiovascular events in individuals with diabetes. Diabetologia (2008) 51:385–390 DOI 10.1007/s00125-007-0898-3
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