Secondary stroke prevention: inside the vessels and beyond

Cerebral ischaemic stroke is frequently a relapsing, if not chronic, disease. Its incidence is age-dependent, and with the ageing of society the need for effective therapies increases.This review considers current and alternative hypotheses underlying secondary prevention of stroke. Currently, secondary stroke prevention is widely practiced with aspirin (acetylsalicylic acid), a drug that has been in use for more than 100 years. Newer drugs such as ticlopidine and clopidogrel have subsequently been developed, but their efficacy barely surpasses that of aspirin. Other drugs used in secondary stroke prevention include HMG-CoA reductase inhibitors and antihypertensive agents.The endovascular paradigm has shaped the thinking of secondary stroke prevention, and aspirin, ticlopidine and clopidogrel are known as 'platelet inhibitors'; however, their pharmacological and clinical effects are not fully explained within the platelet paradigm. Moreover, in recent years, reduction of stroke incidence has also been observed with HMG-CoA reductase inhibitors, regardless of their lipid-lowering effects. Hence, current understanding needs to be supplemented by considering mechanisms beyond platelet inhibition. Evidence has shown that aspirin, ticlopidine and clopidogrel share neuroprotective properties not explained by the platelet paradigm and that are reminiscent of a preconditioning effect. This neuroprotective mechanism is also shared with HMG-CoA reductase inhibitors.