http://www.theheart.org/article/1338803.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120111_EN_Heartwire
A new meta-analysis said to provide "the largest evidence to date regarding the wider effects of aspirin treatment in primary prevention" has shown that cardiovascular benefits are offset by an elevated risk of bleeding [1].
Senior author Dr Kausik Ray (St George's University of London, UK) commented to heartwire: "On a routine basis I would not recommend aspirin use in primary prevention. And it certainly should not be put in a polypill for mass use."
The current study did not find a significant reduction in cancer mortality. However, the lead author of a previous meta-analysis that did show a reduction in cancer death with aspirin says follow-up in the current study was not long enough to show such an effect.
The new analysis, published online January 9, 2012 in the Archives of Internal Medicine, included nine randomized placebo-controlled trials with a total of 100 000 participants. Results showed that during a mean follow-up of six years, aspirin treatment reduced total cardiovascular events by 10%, driven primarily by a reduction in nonfatal MI, but there was a 30% increased risk of nontrivial bleeding events. The number needed to treat to prevent one cardiovascular event was 120, compared with 73 for causing a nontrivial bleed.
Effect of aspirin on vascular and nonvascular outcomes or death| Event | Odds ratio (95% CI) |
| Cardiovascular events | 0.90 (0.85-0.96) |
| Nonfatal MI | 0.80 (0.67-0.96) |
| Cardiovascular death | 0.99 (0.85-1.15) |
| Cancer mortality | 0.93 (0.84-1.03) |
| Nontrivial bleed | 1.31 (1.14-1.50) |
Possible benefit in those at high risk
The authors conclude that the "rather modest benefits" and the significant increase in risk of bleeding do not justify routine use of aspirin in the primary-prevention population. They say that further study is needed to identify subsets that may have a favorable risk/benefit ratio. They note that their results suggest an increased risk of nontrivial bleeding in individuals receiving daily (vs alternate-day) aspirin treatment and a particularly unfavorable risk/benefit ratio for individuals at lower baseline cardiovascular risk.
An editorial accompanying the paper suggests that aspirin may be considered in patients with a CHD risk of more than 1% per year [2], but Ray said he thought that was an "oversimplification" of the results.
"There may be a benefit in higher-risk individuals, and there is a case for personalized medicine here. But we showed that as the event rate increased in the placebo group, the reduction in MI with aspirin also increased, but so too did the bleeding risk. The bleeding risk is always greater than the MIs prevented, but it depends on whether you think a nonfatal MI is worse than a significant bleed. So we could do better if we knew who would bleed and who would have an event. I think we need a dual risk score as is done for warfarin."
The cardiovascular results from this latest analysis are in line with those from the 2009 Antithrombotic Trialists' (ATT) Collaboration, and there seems to be agreement on the conclusions regarding heart disease. But there is less agreement on the use of aspirin for the prevention of cancer.
Disagreement over cancer data
Lead author of last year's analysis showing a reduction in cancer mortality with aspirin, Dr Peter Rothwell (University of Oxford, UK) commented to heartwire: "This new meta-analysis just looks at the overall study results, and most of the studies only had three to four years of follow-up. That is not long enough to see a major effect on cancer mortality. In contrast, in our meta-analysis published last year we obtained individual patient data and followed patients long-term after the trials had finished, and in this way we were able to show a significant and impressive effect on cancer mortality."
Rothwell estimates that it takes at least five years to show an effect on cancer deaths, "but after this point you see quite an impressive effect." He noted that the new study also included both alternate and daily aspirin trials, but "all previous work has suggested that aspirin needs to be given every day to prevent cancer."
He added: "Their results are completely compatible with our results. They did show a trend toward a reduction in cancer mortality, which we believe would have become significant if they had longer-term data or if they looked at individual patient data."
The UK newspapers were today full of reports saying there is no benefit of aspirin in cancer prevention, exactly the reverse of the headlines after Rothwell's study came out last year. Rothwell says he is concerned about this. "The message today that aspirin does not prevent cancer is premature. The current study should not change advice on taking aspirin as a healthy person. It does not offer any additional information that we don't already know. We need to think about both risk of heart disease and cancer, and in general heart disease risk is coming down while cancer risk is increasing. There does appear to be a cancer benefit with long-term use, so if there is a family history of cancer I would think about taking aspirin. We have more studies with individual patient data coming out soon that will shed more light on the issue."
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