Secondary Prevention of Stroke and Transient Ischemic Attack

Abstract

Background— Recurrent cerebrovascular events constitute an estimated 200 000 of the 700 000 strokes reported annually in the United States, which makes secondary stroke prevention an important goal in the management of disease among patients who have experienced stroke or transient ischemic attack. Methods and Results— Various pharmacological approaches have been advocated, but the relative efficacy and safety of these regimens has remained the subject of much debate. The results of recent clinical trials on the use of antiplatelet therapy suggest that patients with a history of stroke or transient ischemic attack may constitute a population distinct from patients with coronary or peripheral vascular disease. This may be caused, in part, by the differing etiologies of stroke and the increased vulnerability of cerebral vessels to bleeding. Indeed, dual antiplatelet therapy, which has been found to be beneficial for the treatment of acute coronary syndromes and percutaneous coronary interventions, does not confer secondary stroke protection. The emerging paradigm is that some level of platelet inhibition is required for secondary stroke protection; a level beyond which increased risk of bleeding arises. Conclusion— Because the vast majority of patients with ischemic stroke have recurrent stroke or transient ischemic attack, rather than myocardial infarction, as their next event, antiplatelet therapies for these patients should be administered according to what has been shown to be efficacious for secondary stroke protection rather than for myocardial protection. Combination therapies, which provide optimal platelet inhibition as well as vascular protection, may offer the best strategy for secondary stroke protection.

Secondary Stroke Prevention, and the Role of Antiplatelet Therapies

“…5 A post-hoc analysis of ESPS-2 data showed no increase in risk for MI, angina, or mortality among cardiac patients in the study who received ER-DP. 12 A recent open-label study confirmed the findings of ESPS-2. The ESPRIT trial randomized 2739 patients with recent TIA or minor ischemic stroke to ASA or ASA + ER-DP (separately or as fixed-dose combination).…”

Reperfusion of cerebral artery thrombosis by the GPIb–VWF blockade with the Nanobody ALX-0081 reduces brain infarct size in guinea pigs

“…1,2 Inhibition of platelet activation is a crucial strategy for the control of ischemic cardiovascular disease, [3][4][5] but a limitation of currently used platelet inhibitors is that they not only prevent thrombosis in injured arteries but they also prevent normal hemostasis, thus increasing bleeding. 6 An increased bleeding risk is particularly ominous when treating ischemic cerebrovascular disease because of the harmful consequences of intracranial hemorrhage; 7 therefore, ischemic cerebrovascular disorders represent a clinical setting in which an antiplatelet regimen with a lower bleeding risk would be of special value. 8,9 Antiplatelet therapy with aspirin, dypiridamole, clopidogrel, or their combination is the mainstay for secondary prevention of stroke, but its effectiveness for acute stroke is limited and is associated with increased intracranial bleeding.…”

Comparative effects of cilostazol and aspirin on the impairment of endothelium-dependent cerebral vasodilation caused by acute cigarette smoking in rats

“…Avoiding cerebral hemorrhage is crucial during therapy aimed at preventing a further ischemic stroke. However, the prevention of ischemic stroke differs from the prevention of cerebral hemorrhage as regards the effective therapeutic regimens, and cerebral vessels may be more liable than vessels from other vascular beds to suffer bleeding during antiplatelet therapy [9]. In Fig.…”

“…Although antiplatelet drugs such as aspirin are considered to be effective at preventing a recurrence of cerebral infarction, use of aspirin is associated with an elevated risk of hemorrhagic complications [9]. Interestingly, a recent report indicated that while another antiplatelet drug, cilostazol, was highly effective at reducing the risk of a subsequent cerebral infarction, hemorrhagic events occurred only rarely with cilostazol [10].…”