The action of dipyridamole to prevent thrombosis: Practical implications for the treatment and prevention of stroke

Abstract

Aggrenox (Boehringer Ingelheim, Ingelheim, Germany), a novel combination of low-dose aspirin with dipyridamole, represents a safe and promising combination alternative for mild but sustained platelet inhibition, and reduction of both arterial and venous thrombi occurrences. In a large, well-controlled randomized trial (ESPS-2 ) evaluating antiplatelet agents for stroke prevention, Aggrenox was twice as effective as monotherapy with either aspirin or dipyridamole. There is an increasing body of evidence that a delicate strategy with Aggrenox provides modest inhibition of platelet activity, especially in a chronic, long-term setting. Mild platelet inhibition beyond conventional aggregation may represent a substantial advantage over aggressive antiplatelet regimens for the treatment, and especially for secondary prevention, of cerebrovascular ischemic events. Although there is no doubt that the concept of inhibiting platelets is vital for the treatment of vascular ischemic disease in general and ischemic stroke and transient ischemic attack (TIA) in particular, the optimal degree of such inhibition still remains an unsolved mystery. It seems that the concepts of "the more, the better" and "one size fits all" may no longer be valid for ideal antiplatelet protection in such high-risk populations. Without routine individual laboratory assessment of platelet function, mild regimens have the advantage of being more suitable for the majority of patients and will contribute substantially to the success of dipyridamole. Conversely, if we can determine baseline platelet status and intelligently apply therapy based on platelet activity in each particular patient, clinical outcomes may be better. Avoiding excessive bleeding risks after aggressive strategies in patients with normal or already decreased platelet function, but targeting those who exhibit activated platelets, may improve risk stratification and save lives. Therefore, Aggrenox should be considered a drug of choice to prevent the second stroke. Eliminating, or at least minimizing, the most frequent side effect, namely transitory headaches at the beginning of therapy with Aggrenox, will benefit patients and increase the use of this agent. Should the PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) trial show an advantage in event reduction with Aggrenox over clopidogrel, the increase will be especially dramatic. In short, based on current evidence most guidelines include Aggrenox as a first-line option for secondary prevention of ischemic stroke or TIA, and some recent versions suggest it may be preferable in other clinical scenarios.