9.1 Aspirin

Two primary prevention trials and one trial in hypertension using aspirin have shown significant reductions in the risk of non-fatal myocardial infarction in high risk men: the US Physicians' Health Study;¹³ the Thrombosis Prevention Trial¹⁴ in UK general practice; and the Hypertension Optimal Treatment (HOT) trial.¹³⁵ These trials have not been powerful enough to show an effect on mortality. In the UK trial, aspirin (75 mg/day) was associated with a relative reduction in myocardial infarction of 20% (annual NNT about 400), which should be balanced against a small increased risk of bleeding.¹³⁶ This increased risk of bleeding was higher in the HOT study.¹³⁵ This balance of benefit over risk increases with the absolute risk of myocardial infarction, which can be estimated from, for example, the New Zealand Guidelines¹³⁷ (see the SIGN guideline on Lipids and the Primary Prevention of Coronary Heart Disease¹³⁸). Because aspirin is much cheaper than lipid-reducing drugs, its use should be considered in pharmacological primary prevention of myocardial infarction in those at increased risk,¹³⁶ e.g. 2% per year. Evidence level Ib

The relative reduction in vascular events in diabetics in a pooled analysis of eight trials was similar (annual NNT 360) but was not statistically significant.⁸

Aspirin (75 mg/day) should be considered for primary prophylaxis of myocardial infarction in men at high risk, (e.g. 2% per year) balanced against the increased risks of bleeding.

Aspirin (75 mg/day) should also be considered for primary prophylaxis of myocardial infarction in women at high risk, (e.g. 2% per year) balanced against the increased risks of bleeding. Based on level III evidence and extrapolation of level Ib evidence in men

9.2 Warfarin

The Thrombosis Prevention Trial¹⁴ also assessed the effect of low-dose warfarin (INR 1.3-1.9, mean 1.47) with and without aspirin (75 mg/day) in prevention of ischaemic heart disease (IHD). Low-dose warfarin (without aspirin) was associated with a similar reduction in non-fatal myocardial infarction, and a similar increase in risk of bleeding, as low-dose aspirin. Evidence level Ib

Because of the added workload (need for INR monitoring) compared to aspirin, aspirin is preferred for primary prophylaxis, as for secondary prophylaxis.

Low-dose warfarin combined with aspirin was associated with a greater reduction in myocardial infarction (fatal and non-fatal) than either agent alone (relative risk reduction 34%).¹⁴ However, combined treatment was also associated with significantly greater risk of bleeding, including haemorrhagic stroke. Evidence level Ib

For this reason, as well as the need for INR monitoring, aspirin is again preferred for routine primary prophylaxis. Further research is required to establish whether subgroups derive greater benefit from warfarin.

Low-dose warfarin (target INR 1.6, range 1.3-1.9) is effective in primary prophylaxis of IHD in high risk men. However, the need for INR monitoring and the risk of bleeding, especially when combined with aspirin, render it less attractive than aspirin for routine antithrombotic primary prophylaxis.