The available evidence demonstrates that the use of clopidogrel plus aspirin in people at high risk of cardiovascular disease and people with established cardiovascular disease without a coronary stent is associated with a reduction in the risk of myocardial infa rct ion and ischaemic stroke , and an increased risk of major and minor bleeding compared with aspirin alone .
According to GRADE criteria , the quality of evidence was moderate for all outcomes except all-cause mortality ( low quality evidence ) and adverse events ( very low quality evidence )
BACKGROUND Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease .
Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease .
This is an up date to a previously published review from 2011 .
OBJECTIVES To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease , ischaemic cerebrovascular disease , peripheral arterial disease , or were at high risk of atherothrombotic disease , but did not have a coronary stent .
Randomized controlled trial of aspirin and clopidogrel versus aspirin and placebo on markers of smooth muscle proliferation before and after peripheral angioplasty.
OBJECTIVE In peripheral arterial disease ( PAD ) patients , a limiting factor in the success of percutaneous transluminal angioplasty ( PTA ) is the development of restenosis secondary to vascular smooth muscle cell ( SMC ) proliferation . Following endothelial damage and platelet activation , there is release of factors and adhesion molecules which affect SMC proliferation . The aim of this study was to determine the effect of combination antiplatelet therapy ( clopidogrel and aspirin compared with aspirin and placebo ) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro . We further aim ed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors , which are known to mediate SMC proliferation in experimental models . METHODS Fifty patients were r and omized to receive blinded clopidogrel or placebo , for thirty days , in addition to their daily 75 mg  aspirin .  To measure proliferative capacity , diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells , and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline , one hour pre-PTA , one hour , 24 hours and 30 days post-PTA . Plasma platelet-derived growth factor ( PDGF ) , sE-selectin , intracellular adhesion molecule-1 ( sICAM-1 ) , and von Willebr and factor ( vWF ) were measured by ELISA , at the same five timepoints . Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA . RESULTS ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA . ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups ( P < .001 ) . There was a statistically significant decrease in PDGF ( P = .004 ) , and increase in vWF ( P = .026 ) , following loading with clopidogrel . sICAM-1 levels significantly decreased ( P = .016 ) in the aspirin/placebo group following PTA . There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2 , sICAM-1 , sE-selectin , or vWF . CONCLUSIONS This is the first study to show in-vitro ERK 1/2 activation ( a surrogate marker of SMC proliferation ) increases post-PTA . Combination antiplatelet therapy had no significant effect on this , although it did reduce PDGF . Further work is required to evaluate potential therapeutic treatments , which may reduce peripheral PTA-induced smooth muscle cell activation . CLINICAL RELEVANCE High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting . The restenotic lesion occurs secondary to platelet activation , released circulating factors , and subsequent smooth musclecell proliferation and migration into the intima . Methods to limit the restenotic lesion are poorly understood . This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation . It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy
The available evidence demonstrates that the use of clopidogrel plus aspirin in people at high risk of cardiovascular disease and people with established cardiovascular disease without a coronary stent is associated with a reduction in the risk of myocardial infa rct ion and ischaemic stroke , and an increased risk of major and minor bleeding compared with aspirin alone .
According to GRADE criteria , the quality of evidence was moderate for all outcomes except all-cause mortality ( low quality evidence ) and adverse events ( very low quality evidence )
BACKGROUND Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease .
Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease .
This is an up date to a previously published review from 2011 .
OBJECTIVES To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease , ischaemic cerebrovascular disease , peripheral arterial disease , or were at high risk of atherothrombotic disease , but did not have a coronary stent .