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.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of October 2011. This month there is one technology appraisal that impacts upon primary care.
The ticagrelor for the treatment of acute coronary syndromes (ACS) technology appraisal (PDF) recommends ticagrelor (Brilique®) in combination with low-dose aspirin for up to a year as a possible treatment for some people with acute coronary syndromes.
The guidance defines the characteristics of the patients with ACS who are recommended for treatment noting that although this treatment costs more than other treatments, this was justified by the benefits it provided.
Action: Clinicians should be aware of this guideline. Primary care is likely to be requested to prescribe courses of this treatment to appropriate individuals.
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 Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Quetiapine prolonged release and immediate release (Seroquel XL® and Seroquel IR®) have been rejected for use in the treatment of major depressive episodes in bipolar disorder. The manufacturer did not present a sufficiently robust economic analysis to gain acceptance.
Tadalafil (Adcirca®) has been rejected for the treatment of pulmonary arterial hypertension. The manufacturer failed to make a submission.
Ticagrelor (Brilique®) has been accepted for use, when co-administered with aspirin, in the prevention of atherothrombotic events in adult patients with acute coronary syndromes. When administered with aspirin, ticagrelor demonstrated a significant reduction in ischaemic events compared with another antiplatelet drug without significantly increasing the incidence of study-defined major bleeding. However, the SMC notes that alternative treatments are available at a lower drug acquisition cost.
Tocofersolan oral solution (Vedrop®) has been rejected for the treatment of vitamin E deficiency due to digestive malabsorption in paediatric patients suffering from congenital chronic cholestasis or hereditary chronic cholestasis. The manufacturer did not supply any economic analysis therefore the cost-effectiveness could not be assessed.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.