The Journal of the American Medical Association (JAMA) has published the results of a study that aimed to assess the efficacy of aspirin in preventing primary cardiovascular events in patients with a low ankle brachial index (ABI).
ABI is the ratio of systolic blood pressure at the ankle and arm. ABI is used to diagnose peripheral vascular disease and is associated with an elevated risk of coronary events.
3,350 men and women aged 50 to 75 were recruited to the study. None had clinical cardiovascular disease but all had ABI less than or equal to 0.95. Follow up was for a mean of 8.2 years for a primary composite outcome of fatal or nonfatal coronary event, stroke or revascularisation. Participants were randomly assigned to treatment with 100mg aspirin daily or matching placebo.
The study found no significant difference in the rate of the primary outcome between the two study groups (Hazard Ratio 1.03, 95% confidence interval 0.84 - 1.27). Additionally, there were no differences in the two secondary outcomes (a composite of the primary outcome and angina, intermittent claudication or transient ischaemic attack or all-cause mortality). The study also assessed the rate of major haemorrhage requiring a hospital admission. This was higher in the patients treated with aspirin but the difference was not significant (HR 1.71, 95% CI 0.99 - 2.97).
The authors conclude that among this population "the administration of aspirin compared to placebo did not result in a significant reduction in vascular events". The authors also suggest that ABI assessment is unlikely to be a useful screening tool in primary care settings.
The results of the study may be limited by low levels of medication compliance with the treatments taken for 60% of the trial person-years. Also, the study was designed and powered to detect a 25% relative reduction in events. Recent analyses have indicated that aspirin may only produce a 12% reduction and perhaps this study was underpowered.
Action: This study adds some more weight to the conclusions reached by the Drug and Therapeutics Bulletin that the use of aspirin in the primary prevention of cardiovascular events is unjustified.
The Drugs and Therapeutics Bulletin has published a review of the available evidence for aspirin in the primary prevention of cardiovascular disease (CVD) and concluded that use in this way is unjustified. This advice has been reported in the general media (BBC).
This review considers the recommendations made in various current guidelines and the historical evidence base in comparison to more recent research including the analysis conduct by the Antithrombotic Trialists’ Collaboration and published in the Lancet earlier this year.
A gender specific analysis that is considered found an absolute benefit of 4 cardiovascular events prevented in 1,000 women and 3 prevented in men over a 6.4 year period. This benefit was offset by 2.5 additional bleeding events per 1,000 women and 3 events in men.
These same data can be expressed in terms of number needed to treat (NNT) to prevent a cardiovascular event and number needed to treat to cause a harm (NNH) of a bleeding event. In women the NNT is 333 and the NNH is 400 while in men the figures are 270 and 303 respectively.
The authors of this review conclude that, "the currently available evidence does not justify the routine use of low-dose aspirin for the primary prevention of CVD in apparently healthy individuals, including those with elevated blood pressure or diabetes". They recommend reviewing patients currently taking aspirin for primary prevention and advise against starting any new patients on primary prevention treatment with aspirin.
Action: Clinicians should be aware of this review and the media coverage it has generated. The balance of risk and benefit of aspirin in primary prevention appears to be a very fine line and continued use appears unjustified.
The Lancet has published the results of a meta-analysis that aimed to assess the benefits and risks of aspirin therapy in the primary prevention of vascular events. This study has been reported in the general media (BBC) and builds on previous analyses.
The analysis was conducted by the Antithrombotic Trialists' Collaboration and included data from six trials with 95,000 participants. Aspirin therapy produced a 12% relative risk reduction (absolute risk of 0·51% with aspirin versus 0·57% control per year) in serious vascular events mainly driven by reductions in non-fatal heart attacks. Aspirin treatment also increased major gastrointestinal and extra-cranial bleeds (0·10% versus 0·07% per year). These figures equate to a number needed to treat (NNT) of 1,667 for one year to prevent a serious vascular event compared to a number needed to harm (NNH) of 3,334 for major gastrointestinal and extra-cranial bleeds in the same time period.
The authors conclude that in primary prevention "aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds". They also note that further research is under way.
Action: Clinicians should ensure that other modifiable risk factors (lifestyle, smoking, blood pressure, blood lipids) for cardiovascular events are managed appropriately in individuals who are identified as being at higher risk. Recommendation of aspirin therapy requires a careful consideration of the potential risks and benefits.
The Annals of Internal Medicine has published the results of a post-hoc observational analysis of a randomised controlled trial to assess the optimal dose of aspirin as an anti-thrombotic.
The review assessed the benefits and risks of aspirin at doses of less the 100mg daily and more than 100mg daily. The review found no differences between the two dose classifications in terms of the primary efficacy or primary safety endpoints. In patients who were also taking clopidogrel, there was a trend towards reduced efficacy and increased harm in patients taking more than 100mg of aspirin daily although these results were not statistically significant.
The authors conclude that higher doses of aspirin are associated with "no clear benefit in patients taking aspirin only and possibly with harm in patients taking clopidogrel".
Action: Clinicians should ensure that aspirin is given at a daily dose of 75mg when intended for use as an anti-thrombotic. Higher doses should be used cautiously after careful assessment of potential risks and benefits.
Thanks to Kevin Ashworth for spotting this article
The British Journal of Cancer has published the results of an observational prospective cohort study that aimed to assess between use of non-steroidal anti-inflammatory drugs (NSAIDs) and three types of stomach cancer. This story was reported in the wider media (BBC).
Data were collected for 311,115 individuals on self-reported use of aspirin and other NSAIDs and incidence of gastric non-cardia, gastric cardia and oesophageal adenocarcinomas. Aspirin (HR 0.64, 95% CI 0.47–0.86) or other NSAIDs (0.68, 0.51–0.92) was associated with a significantly lower risk of gastric non-cardia adenocarcinoma. There was no association with the other cancers studied.
The authors note that aspirin significantly increases the risk of gastrointestinal bleeding and haemorrhagic stroke and that these potential cancer benefits do not outweigh these risks. The recommend that further research should be conducted in a randomised controlled trial setting to confirm and quantify these findings.
Action: Clinicians should be aware of this study in light of the significant media coverage. NSAIDs cannot currently be recommended to prevent cancer because the benefits do not appear to outweigh the risks.
Thanks to Kevin Ashworth for spotting this article
