Current Prevention of Secondary Stroke
Ischaemic stroke is a major cause of morbidity and mortality in modern life, ranking as the third most common cause of death after cardiovascular disease and cancer,¹ and its prevalence is expected to rise in line with extended life expectancy.² Eight to 12% of ischaemic strokes result in death within 30 days,³ while surviving patients are at an increased risk of subsequent vascular events, the most common being a second stroke.^4,5 The risk of a recurrent stroke or transient ischaemic attack (TIA) is between 5 and 15% per year and is highest immediately after the primary episode.^6,7 This accounts for approximately threequarters of all secondary vascular events following stroke.⁴ Secondary prevention strategies focus on reducing cardiovascular risk factors such as cigarette smoking, diabetes mellitus (DM), obesity, high blood pressure and increased cholesterol levels.⁸ In addition, pharmacological antiplatelet therapy is indicated in such patients. ASA is the the most widely used treatment. Clinical trials have shown that treating stroke patients with ASA significantly reduces the risk of a recurrent episode compared with placebo.^9–11 However, the absolute risk reduction is low. The protective effect was found not to be dose-dependent, leading to the use of lower doses with a more favourable side effect profile.

To explore other treatment possibilities, later studies compared the efficacy and safety of alternativee antiplatelet drugs with ASA in secondary stroke prevention. The Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial examined the efficacy of clopidogrel compared with ASA in preventing recurrent vascular events among patients suffering from stroke, myocardial infarction (MI) or peripheral arterial disease.¹² Although clopidogrel was found to be more effective among the general study population, this was not significant in the stroke subgroup, and clopidogrel was deemed to be only as good as an ASA in preventing stroke.

The next step towards improving antiplatelet therapy was examining combination treatments. In the Clopidogerl in Unstable Angina to Prevent Recurrent Events (CURE) trial, the combination of clopidogrel and ASA was compared with ASA alone in the prevention of vascular ischaemic events. No significant differences were found in stroke prevention between the treatment groups. Furthermore, patients receiving the combination therapy were at a significantly greater risk of major bleeding.^13,14 The later Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial also looked at the benefit of adding clopidogrel to ASA compared with ASA monotherapy in secondary vascular prevention among a high-risk population. Here, too, no significant differences were found in the rate of cardiovascular disease, but an increase in the risk of major bleeding was evident.