Antiplatelet therapy to prevent recurrent stroke: Three good options
ABSTRACTDrugs that prevent platelets from sticking together—ie, aspirin, dipyridamole, and clopidogrel—are an important part of therapy to prevent recurrence of ischemic stroke of atherosclerotic origin. We discuss current indications for these drugs and review the evidence behind our current use of aspirin, dipyridamole, and clopidogrel.
KEY POINTS
- After a stroke, antiplatelet therapy lowers the rate of recurrent nonfatal stroke by about 25%.
- Aspirin is the most established, best tolerated, and least expensive of the three approved drugs.
- Adding dipyridamole to aspirin increases the efficacy, with a 22% reduction in relative risk, but only a 1% reduction in absolute risk.
- Clopidogrel is similar in efficacy to aspirin and to dipyridamole.
- All three agents are regarded as equal and appropriate for secondary prevention of stroke; the choice is based on individual patient characteristics.
- A small number of strokes result from atherosclerotic disease of the common carotid bifurcation, and patients with symptomatic carotid disease can be treated with the combination of surgery or stenting and drug therapy, or with drug therapy alone.
Aspirin is the best established
Aspirin is the best established, best tolerated, and least expensive of the three contemporary agents. Further, it is also the agent of choice for acute stroke care, to be given within 48 hours of a stroke to mitigate the risk of death and morbidity. The data for other agents in acute stroke management remain limited.38
Aspirin plus dipyridamole
Aspirin plus dipyridamole is slightly more efficacious than aspirin alone, and it is an alternative when aspirin is ineffective and when the patient can afford the additional cost. Aspirin plus dipyridamole offers up to a 22% relative risk reduction (but a small reduction in absolute risk) of stroke compared with aspirin alone, as demonstrated by ESPS-2,14 Leonardi-Bee et al,25 and ESPRIT.26
When is clopidogrel appropriate?
Up to one-third of patients may not tolerate aspirin plus dipyridamole because of side effects. Clopidogrel is an option for these patients. The CAPRIE study29 showed clopidogrel similar in efficacy to aspirin.
In contrast to aspirin plus dipyridamole, there is clearly no benefit to combining aspirin and clopidogrel for ischemic stroke prophylaxis. And data from PRoFESS33 suggested the combination was qualitatively inferior to aspirin plus dipyridamole. However, the PRoFESS trial was underpowered to fully bear this out.
Therefore, current guidelines consider all three agents as appropriate for secondary prevention of stroke. One is not preferred over another, and the selection should be based on individual patient characteristics and affordability.28
CAROTID SURGERY OR STENTING: BENEFITS AND LIMITATIONS
Atherosclerosis is the most common cause of stroke, and atherosclerosis of the common carotid bifurcation accounts for a small but significant percentage of all strokes.39–41
The degree of carotid stenosis and whether it is producing symptoms influence how it should be managed. For patients with symptomatic carotid stenosis of more than 70%, multicenter randomized trials have shown that surgery (ie, carotid endarterectomy) added to medical therapy decreases the rate of recurrent stroke by up to 17% and the rate of combined stroke and death by 10% to 12% over a 2- to 3-year follow-up period (level of evidence A).42–44 No study has proven the efficacy of surgery in patients with symptomatic stenosis of less than 50%.43,44
Similarly, in asymptomatic carotid disease, preventive surgery is a beneficial adjunct to medical therapy in certain patients. An approximate 6% reduction in the rate of stroke or death over 5 years has been shown in patients with moderate stenosis (> 60%), with men younger than age 75 and with greater than 70% stenosis deriving the most benefit.45–47
However, these robust, positive results with surgical intervention should not overshadow the importance of intensive and guided medical therapy, which has been shown to mitigate the risk of stroke.48,49
Is stenting as good as surgery? In the multicenter randomized Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), stenting resulted in similar rates of stroke and MI in patients with symptomatic and asymptomatic disease.50 However, stenting carried a greater risk of perioperative stroke, and endarterectomy carried a greater risk of MI. Those under age 70 benefited more from stenting, and those over age 70 benefited more from endarterectomy.
But another fact to keep in mind is that the relationship between carotid narrowing and an ipsilateral stroke is not necessarily direct. Two follow-up studies in patients from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) found that up to 45% of strokes that occurred after intervention in the distribution of the asymptomatic stenosed carotid artery were unrelated to the stenosis.51,52 Moreover, up to 20% of subsequent strokes in the distribution of the symptomatic artery were not of large-artery origin, increasing up to 35% for those with stenosis of less than 70%.51 Clearly, thorough screening of those with presumed symptomatic stenosis is needed to eliminate other possible causes.
