Patients who have had an ischaemic* stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. In the PERFORM study, published Online First and in an upcoming Lancet, a new drug terutroban was found not to outperform aspirin at preventing a second stroke or TIA. Thus aspirin, one of the cheapest and most widely available drugs in the world, remains the gold standard in terms of secondary stroke prevention worldwide. The Article is by Professor Marie-Germaine Bousser, Hopital Lariboisiere, Paris, and Paris-Diderot University, France, and colleagues.
Previous animal and human research has shown that terutroban is as effective as aspirin in terms of anticlotting (antiplatelet) activity. Findings from experimental studies also suggested that terutroban had potentially beneficial vascular effects, such as reducing artery plaque size and reducing side effects of vascular injury. In this study, terutroban was compared with with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent ischaemic stroke. The primary endpoint was any of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death).
A total of 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean followup was 28 months . The trial was stopped early due to no evidence of benefit for terutroban. The primary endpoint occurred in 11% of patients receiving terutroban and 11% of those receiving aspirin. Some increase in minor bleeding with terutroban occurred, compared with aspirin (12% vs 11%), but there were no significant differences in other safety endpoints.
The authors say: "After the premature discontinuation of PERFORM, the sponsor decided to stop the development of terutroban, including all other terutroban trials in progress… In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost."
In linked Comment, Dr Meng Lee, Chang Gung Memorial Hospital at Chiayi, Chang Gung University College of Medicine, Taoyuan, Taiwan and Dr Bruce Ovbiagele, Department of Neurosciences, University of California, San Diego, CA, USA, ask that trials need to address the question of what to do with patients who do have a second major ischaemic event while being treated on aspirin, since evidence is scarce. They conclude: "Trials that randomly assign patients with a breakthrough event while on aspirin to a newer antiplatelet drug or higher aspirin dose, rather than reinitiation of the original aspirin dose, could provide insights into this issue. Perhaps terutroban could be called on to perform again."
Journal
The Lancet