Add potential Bayer victims: me and you, if you weigh more than 154 pounds and have been taking 81 mg low-dose aspirin to fend off a heart attack. For us >154 pounders, daily low-dose aspirin actually raises the risk of a “first-time cardiovascular event,” according to researchers led by Peter Rothwell of the University of Oxford, in a paper in the Lancet  published online July 12.

Rothwell’s team reviewed 10 relevant studies and summarized their findings thus:

Evidence before this study A one-dose-fits-all approach to use of aspirin has yielded only modest benefits in the long-term prevention of cardiovascular events, possibly due to underdosing in patients of high body size and excess dosing in those of low body size. Randomised trials of aspirin in primary prevention of cardiovascular events have all tested a single dose against a control, but have differed in the dose(s) chosen. We identified ten randomised trials of aspirin in primary prevention (involving 117 279 participants) from the Antithrombotic Trialists’ Collaboration, the Cochrane Collaboration Database of Systematic Reviews, and previous systematic reviews.

Added value of this study In the absence of previous analyses, we used individual patient data from trials of aspirin versus control in the primary prevention of cardiovascular events, stratifying by weight, height, and other measures of body size, to identify whether the effects of high and low doses of aspirin are modified by these variables. We validated findings in trials of aspirin in secondary prevention of stroke, and by determining any weight dependence of the effects of aspirin on long-term risk of colorectal cancer and on short-term risk of all cancer. We found that the ability of low-dose aspirin (75–100 mg) to reduce cardiovascular events declined with increasing weight, with substantial benefit at 50–69 kg but no benefit at 70 kg or more, and with increased case fatality of first cardiovascular events in people weighing 70 kg or more. Higher doses (≥325 mg) of aspirin showed a reverse interaction with weight and height, reducing cardiovascular events only at larger body size. Findings were consistent in men and women, in participants with diabetes, and in trials of aspirin in secondary prevention of stroke. Reductions in long-term risk of colorectal cancer by aspirin were both height and weight dependent. However, stratification by body size revealed harms due to excess dosing, with an increase in sudden deaths at lower weight and an increase in the short-term risk of cancer at lower weight and shorter height in participants aged 70 years or older.

Implications of all the available evidence  The optimal dose of aspirin to prevent cardiovascular events depends on bodyweight, driven more by lean body mass and height than by body-mass index. Once-daily low doses (75–100 mg) of aspirin were ineffective in people weighing 70 kg or more, particularly in those who smoke or were treated with enteric-coated formulations, whereas higher doses became more effective with increasing weight. We also found that the effects of aspirin on sudden cardiac death and cancer showed dose–weight interactions, suggesting that the one-dose-fits-all strategy for daily aspirin is unlikely to be optimal. The substantial reductions in cardiovascular events and death at optimal doses for weight highlight the potential to improve effectiveness and argue for a more tailored dosing strategy.

A daily aspirin dose of 75 -100 milligrams lowers the heart attack risk 23 percent for <154 pounders… but us  >154 pounders who compliantly dropped  low-dose aspirin  all these years have in fact been putting ourselves at increased risk.  Rothwell et al conclude that >154 pounders may require up to 500 mgs/day to achieve cardiovascular benefit from aspirin.

Low-dose aspirin reduced the colorectal cancer risk in people <154 pounds, not in those >154. High doses lowered the  risk in people who weighed between 154 and 176 pounds, but not in those heavier than 176.

You’d think this study would have made the news. Good of the Lancet to make the whole paper available.