Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Aspirin to Prevent Cardiovascular Disease: The Association of Aspirin Dose and Clopidogrel With Thrombosis and Bleeding Extended Duration Dual Antiplatelet Therapy After Coronary Stenting Among Patients With Peripheral Arterial Disease: A Subanalysis of the Dual Antiplatelet Therapy Study. Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent  Update on dual antiplatelet therapy for percutaneous coronary intervention A global view of atherothrombosis: baseline characteristics in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Aspirin resistance and diabetes mellitus Secondary prevention of vascular disease by prolonged antiplatelet treatment Efficacy and safety of 12 versus 48 months of dual antiplatelet therapy after implantation of a drug-eluting stent: the OPTImal DUAL antiplatelet therapy (OPTIDUAL) trial: study protocol for a randomized controlled trial Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery Cost-effectiveness of clopidogrel plus aspirin versus aspirin alone for secondary prevention of cardiovascular events: results from the CHARISMA trial. Enhanced antiplatelet effect of clopidogrel in patients whose platelets are least inhibited by aspirin: a randomized crossover trial. New antiplatelet therapies in development. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial Clopidogrel added to aspirin adds no benefit but bleeding risk in patients with recent lacunar stroke. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Platelet reactivity and cardiovascular events after percutaneous coronary intervention in patients with stable coronary artery disease: the Stent Thrombosis In Belgium (STIB) trial. Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial. Unstable angina, stroke, myocardial infarction and death in aspirin non‐responders. A prospective, randomized trial. The ASCET (ASpirin non‐responsiveness and Clopidogrel Endpoint Trial) design Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Clopidogrel as adjunctive antiplatelet therapy during coronary stenting.
BACKGROUND Clopidogrel is a more potent antiplatelet agent than aspirin , result ing in greater clinical efficacy in patients with atherothrombotic disease . Furthermore , the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting . Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown . METHODS AND RESULTS The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) study was design ed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary , cerebral , or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event . This r and omized , international , multicenter , double-blinded , placebo-controlled study has finished enrolling patients worldwide . A total of 15,603 patients will be followed long term . The primary end point will be the composite of vascular death , myocardial infa rct ion , or stroke . Rates of severe bleeding will also be compared between the two arms of the study . CONCLUSIONS This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current st and ard of care , including low-dose aspirin , for a wide spectrum of patients with atherothrombosis The American Heart Association/American Stroke Association ( AHA/ASA ) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack ( TIA ) has review ed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data , to up date specific recommendations , and to provide the reasons for any modifications . The 2 areas in which major new clinical trials have been published are ( 1 ) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and ( 2 ) the use of statins in the prevention of recurrent stroke . Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA . The secondary prevention guidelines 1 have been up date d to reflect this new evidence . # # # Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events ( CHARISMA ) trial2 was a double-blinded study that r and omized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin ( 75 to 162 mg ) or placebo plus aspirin ( 75 to 162 mg ) . Roughly 35 % of subjects ( n=4320 ) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment ; approximately a third experienced TIA . The median follow-up was 28 months . No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups ( 1.7 % versus 2.1 % , P = 0.07 ) . The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group ( 1.9 % versus 2.4 % , P = 0.03 ) . The 2 groups experienced no differences in the rate of intracerebral hemorrhage Context The optimal aspirin dose for prevention of cardiovascular events is unknown . Contribution This post hoc analysis of CHARISMA trial data suggests no overall differences in efficacy or safety by aspirin dose . However , in the subgroup of patients r and omly assigned to clopidogrel , there was a hint of reduced efficacy and increased harm with higher doses . Caution Patients were not r and omly assigned to aspirin dose . Implication Lower aspirin doses ( 75 to 81 mg/d ) may optimize efficacy and safety for patients requiring aspirin for long-term prevention , especially those taking clopidogrel .  The Editors Aspirin is the most widely used drug worldwide for the prevention of thrombotic cardiovascular events . Of note , the doses of aspirin used most often clinical ly or recommended in guidelines are based not on the results of trials design ed to identify the most efficacious or safest dose , but on a combination of historical precedents and trials in which specific doses of aspirin were m and ated by protocol . This practice has led to a wide range in aspirin doses ( 75 to 325 mg/d ) recommended by the U.S. Food and Drug Administration ( 1 ) for the management of cardiovascular disease in various population s. Although as little as 30 mg of aspirin daily is needed to fully inhibit platelet thromboxane production ( 2 ) , doses more than 10 times higher than this are routinely used in long-term prevention of cardiovascular disease . Because aspirin has been used clinical ly for more than a century and is a mainstay of therapy for patients who have or are at risk for atherosclerotic disease and other common ailments , its risks are often underappreciated . However , given that more than one third of U.S. adults are estimated to take aspirin daily for cardiovascular disease ( 3 ) , even a very small incidence of hemorrhagic complications places a large number of people at risk . Consistent with this is a recent analysis of hospitalizations for adverse drug effects that found aspirin to be one of the most common causal agents ( 4 ) . The gastrointestinal tract is the leading source of bleeding events in  aspirin-treated  patients because of inhibition of gastroprotective prostacyclins , with an excess risk for upper gastrointestinal complications of 5 cases per 1000 aspirin users per year ( 5 ) . Prospect i ve evaluation of  aspirin-treated patients with coronary artery disease identified an incidence of upper gastrointestinal bleeding of 1.5 % per year , with substantial associated morbidity ( 6 ) . Because inhibition of gastric prostacyclin is dose-dependent and not maximal until a daily dose of about 1300 mg is reached ( 4 ) , minimizing the dose of aspirin to that needed to fully inhibit platelet thromboxane production would probably offer the greatest potential benefit with the lowest possible risk . In several observational studies of large prospect i ve trials , lower doses of aspirin ( < 162 mg/d ) have been associated with the lowest incidence of thrombotic events ( 7 , 8) and a trend toward fewer bleeding events ( 8) . These favorable trends in efficacy and safety were confirmed in the CURE ( Clopidogrel in Unstable angina to prevent Recurrent Events ) trial ( 9 ) of dual antiplatelet therapy with clopidogrel plus aspirin versus placebo plus aspirin . On the basis of these results , the design of the CHARISMA ( Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ) trial ( 10 ) , which r and omly assigned 15603 patients at high risk for atherothrombotic events to clopidogrel or placebo in conjunction with aspirin , m and ated a daily aspirin dose of 75 to 162 mg . We performed a post hoc analysis of associations between investigator-determined daily aspirin dose and thrombotic and hemorrhagic outcomes in the prospect i ve CHARISMA trial . Methods The design , methods , and primary results of the CHARISMA study are reported elsewhere ( 10 ) . In brief , CHARISMA was a multicenter , double-blind , r and omized , placebo-controlled trial of long-term clopidogrel ( 75 mg/d ) treatment versus placebo in patients 45 years or older who had established atherosclerotic disease or were asymptomatic but at high risk because of a combination of risk factors . All patients also received low-dose aspirin therapy , which was limited by protocol to between 75 and 162 mg/d . Patients were excluded if they had an established indication for clopidogrel therapy , such as a recent acute coronary syndrome or stent implantation . Clinical follow-up was done at 1 , 3 , and 6 months and every 6 months thereafter until the end of the trial . The actual dose of aspirin being taken was confirmed at each evaluation . The ethics committee at each of the 768 participating hospitals worldwide , as well as the appropriate national ethics committee for each of the 32 participating countries , review ed and approved the study protocol . All patients provided written informed consent before enrollment . The primary efficacy end point was the first occurrence of myocardial infa rct ion , stroke , or cardiovascular death . The primary safety end point was severe or life-threatening bleeding according to the GUSTO-I ( Global Utilization of Streptokinase and TPA for Occluded coronary arteries ) criteria ( 11 ) : intracerebral bleeding or bleeding result ing in substantial hemodynamic compromise requiring treatment . A secondary safety end point was the combined incidence of severe or life-threatening bleeding or moderate bleeding by the GUSTO-I criteria , with moderate defined as bleeding requiring transfusion but not result ing in hemodynamic compromise ( 11 ) . Of note , patients believed to be at high risk for bleeding were excluded from enrollment .  Aspirin dose was not r and omized ; rather , it was selected at the discretion of the treating physician . We prospect ively divided patients into 3 major groups according to clear demarcations in aspirin dose at baseline : less than 100 mg/d , represented almost entirely by doses of either 75 or 81 mg/d ; 100 mg/d ; and greater than 100 mg/d , represented by either 150 or 162 mg/d . We evaluated the relative efficacy and safety of the different doses of aspirin among all patients , and we evaluated the efficacy and safety end points between the treatment ( clopidogrel ) versus placebo groups by aspirin dose category . Statistical Analysis We performed all data analyses on the intention-to-treat population . We performed hypothesis tests by using 2-sided tests at the 5 % significance level . Baseline characteristics were compared by using chi-square tests for discrete variables and t tests for continuous variables . We calculated cumulative KaplanMeier estimates of the event rates and assessed differences in the unadjusted rates of primary efficacy and safety end points across the aspirin groups by using a 2-sided log-rank test . We used log-rank weights to compute a test for trend across aspirin dose categories . We estimated the treatment effect , measured by the hazard ratio and its 95 % CI , by using the Cox proportional hazards model . Multivariable modeling was performed to determine whether aspirin dose was independently associated with the primary efficacy and safety outcomes after controlling for potentially confounding factors . Because patients could have had more than 1 efficacy or safety event , we defined the time to the primary efficacy end point as the first occurrence of myocardial infa rct ion , stroke , or cardiovascular death . We defined the time to the primary safety end point as the first occurrence of severe or life-threatening bleeding according to the GUSTO-I criteria ( 11 ) . We selected variables for inclusion in the models on the basis of differences in baseline characteristics among patients in the 3 aspirin dose categories or their clinical relevance to the outcomes . Covariates included in the multivariable model for the primary efficacy end point were the continuous variables of age , weight , and systolic blood pressure and the categorical variables of sex ; race or ethnicity ( white or Hispanic vs. other ) ; hypertension ; hypercholesterolemia ; history of congestive heart failure ; previous myocardial infa rct ion ; previous stroke ; previous transient ischemic attack ; diabetes mellitus ; atrial fibrillation ; peripheral arterial disease ; diabetic nephropathy ; current smoking ; primary ( vs. secondary ) prevention and past use of statins , nitrates , and antiplatelet agents other than aspirin . We developed models with and without inclusion of interaction terms for r and omized treatment assignment by aspirin dose category . Adjustment variables in the multivariable model for the primary safety end point ( GUSTO-I severe or life-threatening bleeding ) included age and weight as continuous variables and the categorical variables of stable angina with multivessel disease , sex , race or ethnicity ( white or Hispanic vs. other ) , history of congestive heart failure , previous myocardial infa rct ion , previous stroke , previous transient ischemic attack , diabetes mellitus , atrial fibrillation , peripheral arterial disease , diabetic nephropathy , hypertension , hypercholesterolemia , primary prevention ( vs. secondary ) , and current smoking . We developed models with and without inclusion of interaction terms for r and omized treatment assignment by daily aspirin dose category . To adjust for geographical region without estimating its effect , we used region ( categorized as United States , Canada , Western Europe , Eastern Europe , Latin America , Asia and Australia , or Africa ) as a stratification variable in models for both end points . We assessed the interaction of  aspirin dose and r and omized treatment in both models . We calculated and tested the difference between the maximum likelihood ratios with and without 2 interaction terms ( r and omized treatment assignment by daily aspirin dose of 100 mg and greater than 100 mg ) . We assessed proportional hazards by multiplying each covariate by the log of the time to the event . A Wald test was performed to test the linear hypotheses of the regression coefficients . The proportional OBJECTIVES This study sought to determine whether patients with peripheral arterial disease ( PAD ) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD . BACKGROUND Patients with PAD have increased ischemic and bleeding risks after coronary stenting . METHODS The DAPT ( Dual Antiplatelet Therapy ) study r and omized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone . The effects of continued thienopyridine on myocardial infa rct ion ( MI ) or stent thrombosis , major adverse cardiovascular and cerebrovascular events ( death , MI , or stroke ) and bleeding ( GUSTO [ Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries ] moderate or severe ) were assessed among those with versus without PAD . RESULTS Among 11,648 r and omized patients , 649 ( 5.57 % ) had PAD . Between 12 and 30 months , r and omized patients with PAD had higher rates of MI/stent thrombosis ( 6.03 % vs. 2.92 % ; p < 0.001 ) , major adverse cardiovascular and cerebrovascular events ( 11.65 % vs. 4.62 % ; p < 0.001 ) , and bleeding ( 4.86 % vs. 1.74 % ; p < 0.001 ) . Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis ( with PAD , HR : 0.63 ; 95 % CI : 0.32 to 1.22 ; without PAD , HR : 0.53 ; 95 % CI : 0.42 , 0.66 ; interaction p = 0.631 ) , major adverse cardiovascular and cerebrovascular events ( with PAD , HR : 1.06 ; 95 % CI : 0.67 to 1.67 ; without PAD , HR : 0.70 ; 95 % CI : 0.59 to 0.84 ; interaction p = 0.103 ) , and bleeding ( with PAD , HR , 1.82 ; 95 % CI : 0.87 to 3.83 ; without PAD , HR : 1.66 ; 95 % CI : 1.23 to 2.24 ; interaction p = 0.811 ) . CONCLUSIONS Among patients undergoing coronary stenting , those with PAD have more ischemic and bleeding events versus those without PAD . Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD BACKGROUND Dual antiplatelet therapy with aspirin and thienopyridines ( clopidogrel or prasugrel ) is required after placement of coronary stents to prevent thrombotic complications . Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement , even longer duration s may prevent thrombotic events . STUDY DESIGN The Dual Antiplatelet Therapy ( DAPT ) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention ( PCI ) for the treatment of coronary artery obstructive lesions . The DAPT Study is a multicenter , international , r and omized , double-blind , placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent ( DES ) and 5,400 subjects treated with bare-metal stents ( BMS ) .  All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin . After 12 months , subjects who are free from death , myocardial infa rct ion , or stroke ( MACCE ) , repeat revascularization , and GUSTO ( Global Use of Strategies to Open Occluded Coronary Arteries ) moderate or severe bleeding events will be r and omized to receive either 18 additional months of thienopyridine ( clopidogrel or prasugrel ) ( 30 month DAPT arm ) or placebo ( 12 month DAPT arm ) plus aspirin . Co primary end points are MACCE and stent thrombosis . The primary safety end point is GUSTO moderate or severe bleeding . CONCLUSIONS This r and omized trial is design ed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents Platelet activation is central in the vascular response to percutaneous coronary intervention ( PCI ) . In addition , patients with coronary artery disease ( CAD ) , particularly those with an acute coronary syndrome ( ACS ) , have pre-existing platelet hyper-reactivity . Together , these are among the factors that predispose to stent thrombosis ( ST ) . Thus , dual antiplatelet therapy ( DAT ) , which consists of aspirin and a thienopyridine , forms the cornerstone of pharmacotherapy following PCI with the goal of reducing ST , as well as ischaemic events related to the underlying CAD . Adherence to DAT , and the need for a longer duration of treatment , has become even more important for patients receiving drug-eluting stents ( DES ) , as concerns have been raised regarding the increased risk of very late ST ( > 1 year ) with the current generation of stents.1 Table 1 summarises the most recent guidelines on DAT following PCI which have been jointly published by the American College of Cardiology ( ACC ) , American Heart Association ( AHA ) and Society for Cardiovascular Angiography and Interventions (SCAI).2 3 Despite the routine use of clopidogrel , there is uncertainty about the optimal timing , dose and duration of thienopyridine therapy , and there is a lack of consensus on the management of patients requiring non-cardiac surgery or chronic anticoagulation while being treated with DAT . View this table : Table 1 ACC/AHA/SCAI recommendations for the use of antiplatelet agents in patients requiring PCI2 3 Although current practice in many parts of the world is to administer clopidogrel in the catheterisation laboratory at the time of ad hoc PCI , several clinical trials have evaluated the efficacy of pretreatment ( table 2).4–8 Overall , the data suggest a potential benefit of pretreatment with the 300 mg loading dose , though both PCI-CURE and PCI-CLARITY represent analyses in which the decision to perform PCI was made after r and omisation to the two loading strategies . It appears that a 300 mg clopidogrel loading dose needs to be administered at least 6 h prior to BACKGROUND The manifestations of atherothrombosis such as myocardial infa rct ion , ischemic stroke , limb ischemia , or cardiovascular death pose a global health care burden . Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary . We sought to characterize the risk factors and treatments of a diverse contemporary population of patients with atherothrombosis . METHODS The CHARISMA trial has enrolled 15,603 patients from around the world . Patients with established coronary , cerebrovascular , or peripheral arterial disease , or those at high risk of developing atherothrombosis due to multiple risk factors , have been r and omized to receive either the adenosine diphosphate receptor antagonist clopidogrel or placebo , in addition to background therapy with low- to moderate-dose aspirin . RESULTS A high percentage of enrolled patients are being treated with statins and angiotensin-converting enzyme inhibitors . In the CHARISMA population , a total of 75.6 % of the population had an abnormal body mass index : 42.2 % were overweight and 33.4 % were obese , with particularly high rates in the United States , especially of morbid obesity . Correspondingly , the prevalence of diabetes was 42 % . CONCLUSION The CHARISMA trial will further characterize atherothrombosis and provide insight into the role of dual antiplatelet therapy in improving outcomes in patients with multiple risk factors or established vascular disease . Of note , the rates of obesity and diabetes in patients with atherothrombosis throughout the world are particularly alarming Despite multiple interventions to reduce the risk of cardiovascular disease , the majority of people with diabetes develop macrovascular complications , and mortality following myocardial infa rct ion remains unacceptably high [ 1 ] . Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease , although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [ 2 ] . In fact , there is little direct evidence supporting its efficacy in this group of patients . Instead , there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes . In a meta- analysis of 287 r and omised trials , antiplatelet treatment ( aspirin in most studies ) reduced the risk of ischaemic events by 22 % , but the risk reduction in the subgroup with diabetes was only 7 % , which was not statistically significant [ 3 ] . This outcome was mirrored in the Primary Prevention Project trial , which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [ 4 ] . Despite this , there are no published studies specifically design ed to evaluate the clinical efficacy of aspirin in individuals with diabetes , a surprising omission in the era of ‘ evidence based ’ medicine . These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of  aspirin  in patients with diabetes compared with a nondiabetic population . Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk — a possibility that has led to the hotly debated concept of aspirin resistance [ 5 , 6 ] . Unfortunately , aspirin resistance suffers from a lack of a st and ardised definition , although now generally thought of as either ( 1 ) reflecting clinical aspirin resistance ( or perhaps , more accurately , treatment failure ) , characterised by the occurrence of a thrombotic episode despite treatment with aspirin ; or ( 2 ) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin . Controversy remains as to the cause of biochemical aspirin resistance , its relevance to clinical outcomes , and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients . All of this highlights the urgent need to underst and the mechanisms that underpin the interactions between diabetes and aspirin , to establish the role of aspirin in particular , and antiplatelet therapy in general , in the amelioration of cardiovascular events in individuals with diabetes . Diabetologia ( 2008 ) 51:385–390 DOI 10.1007/s00125 - 007 - 0898 - Thirty one r and omised trials of antiplatelet treatment for patients with a history of transient ischaemic attack , occlusive stroke , unstable angina , or myocardial infa rct ion were identified . Six were still in progress , and the results of the remaining 25 were review ed . They included a total of some 29 000 patients , 3000 of whom had died . Overall , allocation to antiplatelet treatment had no apparent effect on non-vascular mortality but reduced vascular mortality by 15 % ( SD 4 % ) and non-fatal vascular events ( stroke or myocardial infa rct ion ) by 30 % ( 4 % ) . This suggested that with good compliance these treatments might reduce vascular mortality by about one sixth , other vascular events by about a third , and total vascular events by about a quarter . There was no significant difference between the effects of the different types of  antiplatelet treatment tested ( 300 - 325 mg aspirin daily , higher aspirin doses , sulphinpyrazone , or high dose aspirin with dipyridamole ) , nor between the effects in patients with histories of cerebral or cardiac disease . Thus antiplatelet treatment can reduce the incidence of serious vascular events by about a quarter among a wide range of patients at particular risk of occlusive vascular disease . The balance of risk and benefit , however , might be different for “ primary ” prevention among people at low absolute risk of occlusive disease if antiplatelet treatment produced even a small increase in the incidence of cerebral haemorrhage Background Dual antiplatelet therapy with aspirin and thienopyridine is required after placement of coronary drug-eluting stents ( DES ) to prevent thrombotic complications . Current clinical guidelines recommend at least 6 to 12 months of treatment after a DES implantation , but it may be beneficial to apply dual antiplatelet therapy for a longer duration . Methods / design The optimal dual antiplatelet therapy ( OPTIDUAL ) study aims to compare the benefits and risks of dual antiplatelet therapy applied for either 12 or 48 months . We will examine the occurrence of major adverse cardiovascular and cerebrovascular events ( MACCE ) in patients undergoing percutaneous coronary intervention with DES for the treatment of coronary lesions . The OPTIDUAL study is an open-label multicenter , r and omized , national trial that will include 1,966 patients treated with DES . All patients will be treated with dual antiplatelet therapy for 12 months ( + /− 3 ) . Then , patients with no MACCE or major bleeding will be r and omized to receive either 36 additional months of clopidogrel plus aspirin or aspirin only . The primary end-point is the combination of death from all causes , myocardial infa rct ion , stroke and major bleeding . The secondary end points include the individual components of the primary end-point , stent thrombosis , repeat revascularization of the treated vessel and minor bleeding . Discussion This r and omized trial is design ed to assess the benefits and safety of 12 versus 48 months of dual antiplatelet therapy in patients that receive a DES . We aim to determine whether substantial prolongation of clopidogrel ( a thienopyridine ) after DES implantation offers an advantage over its discontinuation . Trial registration Clinical Trials.gov Identifier : Coronary artery bypass grafting (CABG)-related bleeding complications and perioperative coronary events are strongly influenced by the management of antithrombotic therapy before and after CABG . Bleeding but also blood products transfusion increase the risk of death and compromise the long-term benefits of CABG.1 The use of new P2Y12 inhibitors , increasing pre-CABG percutaneous coronary interventions ( PCI ) with drug eluting stents ( DES ) requiring specific antiplatelet regimens , and advances in surgical technique has prompted the ESC Working Group on Cardiovascular Surgery and the ESC Working Group on Thrombosis to review the evidence of peri-CABG recommendations on antithrombotic management . Due to the paucity of r and omized trials , most of the evidence is still derived from observational studies and expert consensus , further reinforcing the importance of a multidisciplinary consultation for optimal decision making . # # # Benefits of preoperative aspirin Aspirin ( acetylsalicylic acid , ASA ) is recommended as secondary prevention therapy for all patients with proven coronary artery disease ( CAD ) and without contraindications . Its indication is even stronger for post-CABG patients ( recommendation IA).2 The general consensus is that ASA treatment withdrawal has ominous prognostic implication s in patients with CAD , especially in those with intracoronary stents , and should be advocated only when the bleeding risk clearly outweighs that of atherothrombotic events.3 The benefits of continuing ASA until the day of CABG ( ‘ preoperative ASA ’ ) are less clear and may explain the wide variability in the management of ASA therapy in the perioperative period and differences between guidelines endorsed by different professional and scientific societies ( Supplementary material online , Table S1 ) . This was based on the demonstration that ASA started the day before surgery was no more effective than ASA started 6 h after surgery at improving early ( 7- to 10-day ) graft patency , but was associated with increased bleeding complications.4 More recent evidence suggests , however , that ASA use within 5–7 days prior to CABG OBJECTIVE To determine the incremental cost-effectiveness of clopidogrel plus aspirin ( C + A ) compared with aspirin ( A ) alone during the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ( CHARISMA ) trial from a US payer perspective . BACKGROUND Although the CHARISMA trial did not find a benefit of adding clopidogrel to aspirin in its overall study cohort , a benefit was suggested in a prespecified subgroup of patients with established cardiovascular ( CV ) disease . The cost-effectiveness of dual antiplatelet therapy in this population is unknown . METHODS Medical re source utilization was assessed prospect ively , and costs for hospitalizations , physician services , outpatient care , and medications were assigned using 2007 US dollars . Life expectancy was estimated contingent on fatal and nonfatal CV events using statistical models of long-term survival from the Saskatchewan Health data base . RESULTS C + A was associated with a 12.5 % relative reduction in CV death , myocardial infa rct ion , or stroke compared with A alone ( 6.9 % vs. 7.9 % , P = 0.048 ) over a median 28 months of follow-up . Severe or moderate bleeding events were higher in patients receiving C + A versus A alone ( 3.6 % vs. 2.5 % , P < 0.001 ) . Mean cost/patient was $ 2607 higher for C + A , while projected life expectancy increased by an average of 0.072 years due to fewer in-trial events . The result ing incremental cost-effectiveness ratio ( ICER ) for C + A was $ 36,343/year of life gained . Findings were insensitive to discount rate , life expectancy projections , post-event costs , and indirect costs from lost productivity ; the ICER was most sensitive to the cost of clopidogrel . Bootstrap analysis demonstrated that the ICER for C + A remained < $ 50,000/life-year gained in 70.6 % of bootstrap replicates and < $ 100,000/life-year gained in 87.4 % . CONCLUSIONS Among patients with established CV disease , adding clopidogrel to aspirin appears to increase life expectancy modestly at a cost generally considered acceptable within the US health-care system OBJECTIVE We aim ed to determine whether adding clopidogrel to aspirin in patients at high risk of future cardiovascular events would suppress laboratory measures of the antiplatelet effects of aspirin ; and have greater platelet inhibitory effects in patients with the least inhibition of platelets by aspirin . METHODS We performed a r and omized , double-blind , placebo-controlled , crossover trial , comparing clopidogrel 75 mg day(-1 ) versus placebo , in 36 aspirin-treated patients with symptomatic objective ly confirmed peripheral arterial disease . RESULTS The addition of clopidogrel to aspirin did not suppress platelet aggregation induced by arachidonic acid , urinary 11 dehydro thromboxane B2 concentrations , or soluble markers of platelet activation markers ( P-selectin , CD40-lig and ) and inflammation ( high sensitivity serum C-reactive protein , interleukin-6 ) . Clopidogrel significantly inhibited platelet aggregation induced by ADP ( reduction 26.2 % ; 95 % CI : 21.3 - 31.1 % , P < 0.0001 ) and collagen ( reduction 6.2 % ; 95 % CI : 3.2 - 9.3 % , P = 0.0003 ) . The greatest inhibition of collagen-induced platelet aggregation by clopidogrel was seen in patients with the least inhibition of arachidonic acid induced aggregation by aspirin [ lower tertile of arachidonic acid-induced platelet aggregation : 2.8 % ( 95 % CI : -0.8 to 6.3 % ) reduction in mean collagen-induced aggregation by clopidogrel ; middle tertile : 4.0 % ( 95 % CI : 0.4 - 7.6 % ) ; upper tertile 12.6 % ( 95 % CI : 4.5 - 20.8 % ) ; P-value for interaction 0.01 ] . CONCLUSIONS The greatest platelet inhibitory effect of clopidogrel occurs in patients with the least inhibition of arachidonic acid-induced platelet aggregation by aspirin . This raises the possibility that the clinical benefits of adding clopidogrel to aspirin may be greatest in patients whose platelets are least inhibited by aspirin . Confirmation in clinical outcome studies may allow these patients to be targeted with antiplatelet drugs that inhibit the ADP receptor , thereby overcoming the problem of laboratory aspirin resistance PURPOSE The efficacy and safety of new antiplatelet therapies , as well as antiplatelet therapies in development , are review ed . SUMMARY Variability in the response to treatment with aspirin has been recognized for more than 40 years . Thienopyridine antiplatelet agents are now a st and ard pharmacologic component in the management of patients undergoing percutaneous coronary intervention ( PCI ) and stent placement . However , investigators have recently described wide inter-individual variability in the level of platelet inhibition following treatment with the thienopyridine clopidogrel , with a small number of patients classified as " non-responders " or " resistant . " Such variability in response is likely to have important clinical implication s , because antiplatelet therapy plays a key role in the prevention and treatment of cardiovascular disease , For example , recent studies have demonstrated that diminished response to clopidogrel may be associated with increased cardiac events after PCI . Even with larger-than-approved loading doses , clopidogrel requires several hours to reach a steady-state effect , and therapy must be discontinued for several days prior to surgery in order to avoid major bleeding events . Clinical trials of prasugrel , a new oral thienopyridine with a more rapid onset of platelet inhibition , have demonstrated significant reductions in adverse cardiovascular outcomes and stent thrombosis ; however , there is an increased risk for major bleeding events with prasugrel in some subgroups of the study population s. These limitations have led to development of agents that may potentially overcome such clinical challenges . AZD6140 , a novel , potent oral P2Y12 antagonist , demonstrated more effective platelet inhibition versus clopidogrel in a large r and omized trial of patients with acute coronary syndrome . However , patients taking AZD6140  reported dyspnea significantly more frequently than those taking clopidogrel . Cangrelor , a novel intravenous P2Y(12 ) receptor antagonist with a rapid onset of action and complete reversibility of platelet inhibition within 20 - 50 minutes of administration , may offer advantages over currently approved antiplatelet therapies . A new oral antiplatelet thrombin-receptor antagonist , TRA-SCH 530348 , is in early clinical trials . Unlike currently available drugs , TRA-SCH 530348 effectively prevents thrombin-induced activation of platelets . CONCLUSION Each new class of antiplatelet therapies has the potential for specific benefits and adverse effects in clinical use BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications , yet the benefits and risks of treatment beyond 1 year are uncertain . METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed . After 12 months of treatment with a thienopyridine drug ( clopidogrel or prasugrel ) and aspirin , patients were r and omly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months ; all patients continued receiving aspirin . The co primary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events ( a composite of death , myocardial infa rct ion , or stroke ) during the period from 12 to 30 months . The primary safety end point was moderate or severe bleeding . RESULTS A total of 9961 patients were r and omly assigned to continue thienopyridine treatment or to receive placebo . Continued treatment with thienopyridine , as compared with placebo , reduced the rates of stent thrombosis ( 0.4 % vs. 1.4 % ; hazard ratio , 0.29 [ 95 % confidence interval { CI } , 0.17 to 0.48 ] ; P<0.001 ) and major adverse cardiovascular and cerebrovascular events ( 4.3 % vs. 5.9 % ; hazard ratio , 0.71 [ 95 % CI , 0.59 to 0.85 ] ; P<0.001 ) . The rate of myocardial infa rct ion was lower with thienopyridine treatment than with placebo ( 2.1 % vs. 4.1 % ; hazard ratio , 0.47 ; P<0.001 ) . The rate of death from any cause was 2.0 % in the group that continued thienopyridine therapy and 1.5 % in the placebo group ( hazard ratio , 1.36 [ 95 % CI , 1.00 to 1.85 ] ; P=0.05 ) . The rate of moderate or severe bleeding was increased with continued thienopyridine treatment ( 2.5 % vs. 1.6 % , P=0.001 ) . An elevated risk of stent thrombosis and myocardial infa rct ion was observed in both groups during the 3 months after discontinuation of thienopyridine treatment . CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent , as compared with aspirin therapy alone , significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding . ( Funded by a consortium of eight device and drug manufacturers and others ; DAPT Clinical Trials.gov number , NCT00977938 . ) BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin Patients with transient ischemic attack or ischemic stroke have a high risk of recurrent stroke .  Antiplatelet therapy has shown efficacy in secondary stroke prevention and is recommended by guidelines .1–3 In patients without cardiac source of embolism  aspirin , clopidogrel or the combination of aspirin and dipyridamole is recommended . In cardiology , the combination of aspirin and clopidogrel was superior to aspirin monotherapy in the prevention of vascular events after acute coronary syndrome4 but carried a higher bleeding risk . In patients with atrial fibrillation the combination of aspirin plus clopidogrel was superior to aspirin alone in preventing strokes,5 but was again associated with a significant higher risk of major bleeds . In early secondary stroke prevention after transient ischemic attack or minor stroke combination , antiplatelet therapy seems to be superior to monotherapy , but larger r and omized trials are needed.6,7 Combination antiplatelet therapy carries a consistent higher risk of major bleeding complications than monotherapy . Therefore , the possible benefit of a reduction in vascular events has to be balanced against the bleeding risk , especially in stroke patients . In the Management of Atherothrombosis with Clopidogrel in High-risk patients ( MATCH ) trial , aspirin plus clopidogrel was investigated against aspirin monotherapy in high-risk patients with recent transient ischemic attack or ischemic stroke.8 Similar to the Secondary Prevention of Small Subcortical Strokes ( SPS3 ) trial , patients with a cardiac source of embolism and significant carotid stenosis requiring surgery were excluded . About 50 % of patients were categorized to have small vessel disease with suspected lacunar strokes , but in contrast to the SPS3 trial , OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed AIMS The Stent Thrombosis In Belgium ( STIB ) trial aim ed to determine whether assessing platelet reactivity ( PR ) in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention ( PCI ) could predict the risk of ischaemic complications and adverse clinical events up to 30 days post PCI . METHODS AND RESULTS PR before intervention was determined in 891 patients undergoing PCI for stable angina pectoris . Twelve to 24 hours before PCI , all patients received a 600 mg clopidogrel dose followed by 75 mg daily , and 500 mg of aspirin followed by 80 - 100 mg daily . Residual PR was assessed by  VerifyNow point-of-care aspirin and P2Y12 assay before PCI . " Non-responders " to antiplatelet therapy were defined as aspirin reaction unit ( ARU ) > 550 and as P2Y12 reaction unit ( PRU ) > 230 . The endpoint of the study was the composite of periprocedural myonecrosis , stent thrombosis , non-fatal myocardial infa rct ion ( MI ) , stroke and death at 30 days in patients with or without high PR . The endpoint was observed in 180 patients : four deaths , one stroke , 11 Q-wave MI , three non-Q-wave MI and 161 periprocedural myonecroses . At multivariate analysis , the endpoint was predicted by total stent length ( OR : 1.020 ) , GFR < 60 ml/min ( OR : 1.87 ) , history of PCI ( OR : 0.58 ) , white blood cell count ( OR : 1.95 ) and diabetes ( OR : 1.83 ) . No significant association was found between residual PR and the primary endpoint or any of its components . CONCLUSIONS PR measured before PCI in stable patients undergoing elective PCI who are preloaded with 500 mg of aspirin and 600 mg of clopidogrel is not predictive of periprocedural myocardial injury or adverse ischaemic complications up to 30 days BACKGROUND Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke , data in peripheral artery disease ( PAD ) are less compelling . Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD , whereas clopidogrel monotherapy may be more effective in PAD . Ticagrelor , a potent , reversibly binding P2Y12 receptor antagonist , is beneficial in patients with acute coronary syndrome and prior myocardial infa rct ion . The EUCLID trial is design ed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events . STUDY DESIGN EUCLID is a r and omized , double-blind , parallel-group , multinational clinical trial design ed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD . Subjects with established PAD will be r and omized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . The primary end point is a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . Other end points address limb events including acute leg ischemia , need for revascularization , disease progression by ankle-brachial index , and quality of life . The primary safety objective is Thrombolysis in Myocardial Infa rct ion-defined major bleeding .  Recruitment began in December 2012 and was completed in March 2014 ; 13,887 patients were r and omized . The trial will continue until at least 1,364 adjudicated primary end points occur . CONCLUSIONS The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel , given as antiplatelet monotherapy , will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD Background —Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease . Despite documented clinical benefit , many patients on aspirin  still experience severe cardiovascular events . Several laboratory reports have shown lack of platelet inhibition in 5–40 % of aspirin‐treated patients , and the term aspirin resistance has been introduced . The clinical relevance of these laboratory findings is , however , still unknown . New antiplatelet drugs have been developed , and the adenosin diphosphate ( ADP ) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile . Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming . New method ologies , like the PFA‐100 ® system , have made such analyses more suitable for clinical use . Design —In the ASCET study , 1000 patients with documented coronary heart disease will be r and omized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment . Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response Coronary artery bypass grafting is pivotal in the contemporary management of complex coronary artery disease . Interpatient variability to antiplatelet agents , however , harbors the potential to compromise the revascularization benefit by increasing the incidence of adverse events . This study was design ed to define the impact of dual antiplatelet therapy ( dAPT ) on clinical outcomes among aspirin-resistant patients who underwent coronary artery surgery .  We r and omly assigned 219 aspirin-resistant patients according to multiple electrode aggregometry to receive clopidogrel ( 75 mg ) plus aspirin ( 300 mg ) or aspirin-monotherapy ( 300 mg ) . The primary end point was a composite outcome of all-cause death , nonfatal myocardial infa rct ion , stroke , or cardiovascular hospitalization assessed at 6 months postoperatively . The primary end point occurred in 6 % of patients assigned to dAPT and 10 % of patients r and omized to aspirin-monotherapy ( relative risk 0.61 , 95 % confidence interval 0.25 to 1.51 , p = 0.33 ) . No significant treatment effect was noted in the occurrence of the safety end point . The total incidence of bleeding events was 25 % and 19 % in the dAPT and aspirin-monotherapy groups , respectively ( relative risk 1.34 , 95 % confidence interval 0.80 to 2.23 , p = 0.33 ) . In the subgroup analysis , dAPT led to lower rates of adverse events in patients with a body mass index > 30 kg/m(2 ) ( 0 % vs 18 % , p < 0.01 ) and those < 65 years ( 0 % vs 10 % , p = 0.02 ) . In conclusion , the addition of clopidogrel in patients found to be aspirin resistant after coronary artery bypass grafting did not reduce the incidence of adverse events , nor did it increase the number of recorded bleeding events . dAPT did , however , lower the incidence of the primary end point in obese patients and those < 65 years OBJECTIVES We examined the procedural and 30-day clinical outcomes among patients receiving aspirin and either ticlopidine or clopidogrel during coronary stenting . BACKGROUND Ticlopidine-plus-aspirin has become st and ard antiplatelet therapy for the prevention of thrombotic complications after coronary stenting . Clopidogrel has a similar mechanism of action as ticlopidine , but both its efficacy and its safety as a pharmacologic adjunct to coronary stenting have not been well described . METHODS This single-center , prospect i ve analysis examined the in-hospital procedural and 30-day clinical outcomes among 875 consecutive patients undergoing coronary stenting who received adjunctive aspirin and either clopidogrel ( n = 514 ; 58.7 % ) or ticlopidine ( n = 361 ; 41.3 % ) therapy . RESULTS Procedural success rates were similar among the clopidogrel- ( 99.6 % ) and ticlopidine-treated patients ( 99.4 % ) . Subacute stent thrombosis ( i.e. , > 24 h < or = 30 days ) occurred in one clopidogrel-treated ( 0.2 % ) and in one ticlopidine-treated ( 0.3 % ) patient ( p = 0.99 ) . By 30 days following the index procedure , the combined rates of death , nonfatal myocardial infa rct ion and need for target vessel revascularization were similar among patients who received either clopidogrel ( 2.1 % ) or ticlopidine ( 1.4 % ; p = 0.57 ) therapy . CONCLUSIONS In this analysis the antiplatelet combination therapy of aspirin-plus-clopidogrel was an effective regimen for preventing thrombotic complications and major adverse cardiovascular events among a broad spectrum of patients undergoing coronary artery stenting
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 .