Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke

Abstract

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk IL-6 also increases endothelial production of the fibrinolytic inhibitor, plasminogen activator inhibitor type 1 (PAI-1). We assessed the effects of aspirin, clopidogrel and dipyridamole on a panel of the above soluble markers of vascular function in normal volunteers and patients with a prior history of ischaemic stroke. We also assessed the effect of combining the three antiplatelet agents on the soluble markers since we have shown previously that three drugs may be superior to one or two in inhibiting platelet function in vitro. 15Page 4 of 15 METHODS DesignTwo randomised, outcome-blinded, multiway, crossover trials of antiplatelet therapy were performed in normal volunteers and patients with prior ischaemic stroke. The study design has been published previously 16 in a report of the effect of aspirin, clopidogrel and dipyridamole on the function of circulating platelets, phagocytes and their conjugates. SubjectsThe study protocol was approved by the local Research Ethics Committee. All subjects gave written informed consent and the trials were performed according to the that complete data were present for each person; laboratory data from withdrawing subjects are not included in the statistical analyses. Laboratory studySerum and plasma collected into 3.8% sodium citrate (1:9 volume) or 4.0 mmol/L EDTA were centrifuged (1,500g for 15min) within 1 hour of venepuncture. Aliquots were frozen at -80 o C and then assayed in batches using commercially available ELISA kits. CRP (high sensitivity kit, Kalon Biological, Hants, UK) and PDGF (R&D System, Abington, UK) were measured in serum; cGMP (R&D System), vWf (Corgenix, Cambridgeshire, UK), MCP-1 (R&D System) and PAI-1 (Technoclone TC, Surrey, UK)were analysed in citrated plasma. Statistical analysisThe primary analysis compared the presence and absence of each drug on soluble markers, i.e. aspirin versus no aspirin, clopidogrel versus no clopidogrel, and dipyridamole versus no dipyridamole. Secondary analyses compared triple therapy (ACD) versus all other drugs, as before. 16 Analyses were performed using the SAS statistical package.Page 6 of 15 RESULTSDemographic and clinical information for the subjects are given in table 1. The stroke patients are representative of our clinical stroke service and were significantly older and had more risk factors (more hypertension and smokers, higher systolic blood pressure, and elevated total cholesterol) than the volunteers (all p<0.05).When considering the individual effects of the three antiplatelet agents on soluble markers of vascular function, three observations were made. First, dipyridamole significantly reduced plasma vWf levels in ...

Advances in Emerging Therapies 2006

“…The surprising lack of increased bleeding complications is curious, and further claims of antiinflammatory and nonplatelet-mediated benefits of dipyridamole have emerged. 17 The results of ESPRIT confirm those of ESPS 2 18 and have consolidated the position of aspirin and dipyridamole combination therapy as the antiplatelet strategy of choice for secondary prevention of stroke.…”

Clopidogrel Versus Dipyridamole in Addition to Aspirin in Reducing Embolization Detected With Ambulatory Transcranial Doppler

“…Dipyridamole has multiple actions, including inhibition of reuptake of adenosine by red cells and of adenosine deaminase, which both raise extracellular adenosine levels, inhibition of phosphodiesterases raising platelet cyclic guanosine monophosphate and adenosine 3Ј,5Ј-cyclic monophosphate levels, and reduction of circulating von Willebrand factor levels. 18 Therefore, dipyridamole stimulates several endogenous platelet antagonists (adenosine, guanosine 3Ј,5Ј-cyclic monophosphate, adenosine 3Ј,5Ј-cyclic monophosphate). These mechanisms of action explain the platelet results seen in the present trial, namely that clopidogrel was superior at inhibiting ADP-invoked platelet aggregation, whereas the 2 pairs of agents did not differ in their response on collagen-induced aggregation.…”

Myocardial necrosis in patients with thrombotic thrombocytopenic purpura: pathophysiology and rationale for specific therapy

“…Dipyridamole has several other beneficial attributes, including activity as a ROS scavenger, anti-inflammatory effects and potentiation of NO generation (52). Extended release dipyridamole, but not aspirin or clopidogrel, significantly reduced VWF levels in acute stroke and healthy controls (53). However, the value of a small reduction in plasma VWF level in a TTP patient is uncertain.…”