The Lancet has published the results of a meta-analysis that aimed to assess the effects of daily aspirin on cancer incidence, mortality, and non-vascular death. The results of this study have been widely reported in the media (BBC).
This analysis included data from 51 studies involving 77,549 patients. 40,269 were assigned to treatment with aspirin and 37,280 to a control. Trials were included if treatment allocation was random and included an intervention of daily aspirin with a follow up of at least 90 days. The trials were designed to assess cardiovascular outcomes included both primary and secondary prevention of events. The dose of aspirin use varied.
The data were analysed for vascular and non-vascular deaths and cancer death data was accessed at individual patient level where this was possible, otherwise it was extracted from the original trial report or subsequent publications.
Aspirin was reported to reduced cancer deaths (OR 0·85, 95% CI 0·76–0·96, p=0·008) in a dataset involving 34 trials. This became more apparent after 5 years of follow up and onwards (OR 0·63, 95% CI 0·49–0·82, p=0·0005).
In an analysis of primary prevention trials using low dose aspirin cancer risk was reduced from 3 years onwards (OR 0·76, 95% CI 0·66–0·88, p=0·0003) and this effect was present in men and women. It was noted that benefits in reduction of cardiovascular events were offset by an increased risk of major bleeds initially but that over time both of these effects diminished while the cancer benefit appeared to remain.
An analysis to examine consistency across gender, age and smoking status found that the absolute risk reduction is approximately 3 cases per 1000 patient-years across all groups but only after a minimum of three years of treatment.
This analysis does have some limitations. The Women's Health Study was excluded from the analysis as the aspirin was dosed on alternate days; it has not shown a reduction in cancer incidence. The trials were not designed to examine cancer outcomes and in some cases the data for non-fatal cancers was patient reported although this was usually supported by a review of medical records.
The authors conclude that, "prevention of cancer could become the main justification for aspirin" but also note that "more research is required to identify which individuals are likely to benefit most".
An accompanying editorial notes that data are awaited for additional trials. Longer term follow up from the Women's Health Study and Physicians’ Health Study is also awaited, especially as these two studies have not shown a cancer benefit after 10 to 12 years of alternate day dosing of aspirin.
Action: Clinicians should be aware of this recent study and its broad media coverage. The absolute benefit is small; it may be wise to await national guidance before recommending aspirin for use in this way.
The Archives of Internal Medicine has published the results of a new meta-analysis that aimed to assess the net benefit of aspirin in the primary prevention of cardiovascular disease. This study has also been reported in the general media (BBC).
This analysis included data for 102,621 participants from 9 studies that reported event rates for vascular and non-vascular outcomes as well as deaths. It was found that over a mean period of 6.0 years, treatment with aspirin resulted in a 10% reduction in cardiovascular events (OR 0.90, 95% CI 0.85-0.96, NNT = 120) although there was no reduction in cardiovascular deaths.
It was also noted that there was a 31% increase in serious bleeding events (OR 1.31 , 95% CI 1.14-1.50, NNH = 73).
The authors note that the benefits in non-fatal events are offset by clinically important bleeding events and conclude that, "routine use of aspirin for primary prevention is not warranted and treatment decisions need to be considered on a case-by-case basis".
Action: The conclusion of this paper is not new and it is already recommended that aspirin is not used for the primary prevention of cardiovascular events. The data on the event rates in this paper (including the NNT and NNH) may prove useful in communicating the risks and benefits to patients.
NHS Evidence has published Eyes on Evidence for September 2011. This issue includes the results of a meta-analysis into the risks and benefits of aspirin treatment for the primary prevention of cardiovascular disease.
This most recent study was published in the American Heart Journal. Nine trials involving 102,621 patients that ran for an average of 6.9 years were reviewed. Aspirin treatment was associated with a reduction in the composite primary outcome of major cardiovascular events (risk ratio [RR] 0.90, 95% CI 0.85-0.96, P<0.001) but there was no significant reduction for the individual outcomes of myocardial infarction, stroke, ischaemic stroke or all-cause mortality.
Conversely, there was an increased risk of haemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P=0.04) and major bleeding (RR 1.62, 95% CI 1.31-2.00, P<0.001).
The authors also summarise this data over a 5 year period noting that for every 1,000 patients treated aspirin would prevent 2.9 major cardiovascular events but cause 2.8 major bleeds.
The authors conclude that, "the evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk".
NHS Evidence also notes that current 'PolyPill' trials have explicitly not included aspirin in the studies, instead opting for a combination of statins and antihypertensive agents. It is also noted that secondary prevention is a different matter as aspirin is linked with a 15% reduction in subsequent events in such patients.
Action: Clinicians should be aware of UK policy to not use aspirin for primary prevention. Eyes on Evidence may also be a useful resource in maintaining up to date knowledge.
Thanks to Kevin Ashworth for spotting this article
The Lancet has published the results of a meta-analysis that aimed to assess the effect of aspirin in preventing death from cancer. The results of this study have been reported in the general media (BBC).
The review included data from 8 trials involving 25,570 individuals. The aspirin was used in each of these studies to prevent or treat atherosclerotic disease. These studies also collected data on cancer deaths. Individual patient data were available in 7 of the 8 studies.
The results from all 8 studies indicate a 21% relative risk reduction (pooled odds ratio [OR] 0·79, 95% CI 0·68–0·92, p=0·003) while the individual patient data analysis involving 7 studies indicated similar results over 5 years (hazard ratio 0·66, 0·50–0·87, p=0·003).
The data from all 8 studies shows an absolute risk of death from cancer of 3.01% in patient not taking aspirin compared to 2.33% in those assigned to aspirin. This is an absolute risk reduction of 0.68% or a number needed to treat (NNT) of 147 over approximately 5 years to prevent one death from cancer.
This analysis did not make any assessment of the harms of aspirin in this patient group.
Action: Clinicians should be aware of this study. The media reporting may generate patient queries. The chance of benefit is 6 or 7 in 1,000 over 5 years and perhaps more research needs to be done before recommending aspirin as a national cancer prevention strategy.
The British Medical Journal has published a 'Change Page' that reviews the current evidence for aspirin in the prevention of primary cardiovascular events. Change Page articles highlight areas of practice where there is an immediate need for a change in practice to make it consistent with current evidence.
This article notes that recent systematic reviews and meta-analyses have identified that the benefit of using aspirin for primary prevention is much lower than previously assumed and does not appear to outweigh the harms associated with the treatment.
This article also draws attention to the disparate recommendations in current guidelines. For example, a recent update to the Scottish Intercollegiate Guidelines Network (SIGN) Diabetes guideline has stated that "low-dose aspirin is not recommended for the primary prevention of vascular disease in patient with diabetes" while the British Hypertension Society (BHS) has reaffirmed it's recommendation for "low dose aspirin for primary prevention of cardiovascular disease in those for whom the balance of benefit outweighs the risk of harm".
This article urges a review of therapy for all patients taking aspirin for primary prevention and recommends that "the decision to stop or continue treatment should be made with these patients after fully informing them of the available evidence".
Action: Clinicians should not routinely start aspirin for the primary prevention of cardiovascular disease. Patients on current treatment should be reviewed to assess whether continued therapy is justified.