Aspirin for primary prevention of CVD: The controversy remains in diabetes

The role of aspirin for the primary prevention of cardiovascular disease (CVD) in people with diabetes remains a contentious issue. The current consensus is that aspirin should only be offered as primary prevention in people with an elevated risk (>10%) of CVD (Handelsman et al, 2011). Numerous meta-analyses have been conducted to evaluate the safety and efficacy of aspirin for CVD prevention in people with diabetes (Calvin et al, 2009; De Berardis et al, 2009; Younis et al, 2010; Zhang et al, 2010; Butalia et al, 2011). These analyses found no increase in the risk of bleeding with aspirin doses ranging from 100 mg every other day to 650 mg per day. However, no benefit in terms of preventing CVD endpoints, including all-cause mortality, CVD mortality, myocardial infarction and stroke, was identified either.

It would thus appear that aspirin has no benefit in terms of primary CVD prevention; however, these meta-analyses did not include other atherosclerotic endpoints, such as angina, transient ischaemic attack (TIA), peripheral artery disease (PAD) or revascularisation. Consequently, the meta-analysis by Kokoska and colleagues (summarised alongside) sought to evaluate aspirin’s safety and efficacy in the primary prevention of CVD, including a full array of atherosclerotic events, in people with diabetes.

Following an extensive literature search, six studies with a total of 10117 participants were identified as being pertinent to the issues under investigation, with median follow-up ranging from 3.6 to 10.1 years. There was no difference between aspirin and placebo with respect to the risk of all-cause mortality (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.81–1.06) or individual atherosclerotic events. In addition, there was no significant difference in the rates of bleeding (OR, 2.53; 95% CI, 0.77–8.34), gastrointestinal bleeding (OR, 2.14; 95% CI, 0.63–7.33) or haemorrhagic stroke rates (OR, 0.90; 95% CI, 0.34–2.33) between the treatments.

There are some limitations worth noting in this analysis. Firstly, a wide range of aspirin doses was evaluated in the studies, ranging from 100 mg to 625 mg daily. Secondly, not all of the trials assessed or reported all the efficacy and safety endpoints; that is, TIA, PAD and angina were only included in half of the trials, and the safety endpoints of bleeding, gastrointestinal bleeding and intracranial haemorrhage were only included in three trials each. As the number of participants for these endpoints is smaller than for the CVD endpoints, it is difficult to draw conclusions in terms of risk–benefit analysis from such data. A final confounding issue with respect to the safety profile of aspirin is the fact that the intervals between routine assessments in the studies varied from 2 weeks to 2 years, which may have led to under-reporting of adverse events in some studies.

Nevertheless, this meta-analysis helps provide further insight into the role of aspirin in CVD risk management in people with diabetes. The data suggest that aspirin may not be beneficial for the prevention of angina, TIA, PAD or revascularisation, while no evidence of harm due to excess bleeding could be identified.

It remains unclear whether aspirin may be beneficial for primary CVD prevention in certain subsets of people with diabetes; however, the results of studies such as ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes; De Berardis et al, 2007) and ASCEND (A Study of Cardiovascular Events iN Diabetes; ClinicalTrials.gov identifier: NCT00135226) may finally provide definitive answers to this question.

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