One dose of aspirin doesn’t fit all

Daily aspirin reduces blood clots by inhibiting platelets, but yields only modest long-term reductions in heart attacks and strokes, although it remains the most widely used antiplatelet drug in routine practice. 

The researchers suspected that the disparity between the effect of aspirin on platelets in laboratory studies and clinical benefits in practice might be due to the ‘one-dose-fits-all’ approach adopted in trials and practice, with under-dosing at high body-size and excess-dosing at low body-size. They hypothesised that standard low-dose aspirin (i.e. 75-100mg daily), which is widely used in UK and Europe, would be insufficient at high body-size, whereas higher doses (325mg daily is widely used in the USA) would be excessive at lower body-size.

The team, led by Professor Peter Rothwell of Oxford's Nuffield Department of Clinical Neurosciences studied detailed data from their own previous trials (with over 130,000 participants) and showed that standard low-dose aspirin (75-100mg daily) was indeed only effective in preventing heart attacks and strokes in people weighing less than 70kg, with no benefit in the 80% of men and nearly half of women weighing more than 70kg. In contrast, higher doses were only effective at weight above 70kg, and were potentially harmful at lower weight. Effects on other outcomes, including cancer, were also dependent on body size.

As well as showing that prevention of heart attacks, strokes and cancer was substantially more effective at the right dose for weight, the research also identified some previously unrecognised hazards of aspirin, particularly when dose was excessive for weight, with an increase in sudden deaths at lower weight and an increase in the short-term risk of cancer at lower body size in patients aged over 70 years.

Lead researcher, Rothwell, explained that 'The several hundred trials of aspirin in prevention of vascular events have all tested a ‘one-dose-fits-all’ approach, but it appears that this is not a very effective strategy, and might sometimes do more harm than good. Future trials should test strategies in which the dose of aspirin is tailored to the characteristics of the individual patient.'

Writing in the commentary accompanying the paper, Professors Katherine Theken and Tilo Grosser, University of Pennsylvania, conclude that, 'Rothwell and colleagues present provocative results with the potential to substantially impact public health. Clearly, further research is warranted to determine whether weight-adjusted dosing of aspirin should be incorporated into routine clinical care.'

The full paper, 'Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials,' can be read in The Lancet.