Aspirin resistance measured by cationic propyl gallate platelet aggregometry and recurrent cardiovascular events during 4 years of follow-up. Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR) Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Usefulness of aspirin resistance after percutaneous coronary intervention for acute myocardial infarction in predicting one-year major adverse coronary events. Resistance to aspirin in vitro at rest and during exercise in patients with angiographically proven coronary artery disease. Aspirin resistance and diabetes mellitus The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events Relation of aspirin resistance to coronary flow reserve in patients undergoing elective percutaneous coronary intervention. Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer Alternate-day dosing of aspirin in atrial fibrillation. LASAF Pilot Study Group. Risk stratification after coronary artery bypass surgery by a point-of-care test of platelet function. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays: implications for aspirin "resistance". Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting.
BACKGROUND Aspirin resistance appears to be an important prognostic factor in patients with coronary artery disease , yet there is no st and ardized method to measure it and limited data on its correlation to clinical outcomes . METHODS In a prospect i ve study we followed 103 patients ( mean age 64 years ) with acute coronary syndrome ( ACS ) without ST segment elevation who were treated with 100 mg of aspirin ( ASA ) daily . Optical platelet aggregometry using cationic propyl gallate ( CPG ) as an inductor was measured at ACS onset and after 3 , 12 , 24 , 36 , and 48 months . ASA responsiveness was defined both by the slope of the aggregation curve ( < 53%/min ) and by spontaneous aggregation ( < 5 % ) . The primary outcomes were the recurrence of ACS or stroke . RESULTS Patients with ACS exhibited a greater prevalence of  ASA resistance ( 55 % ) than healthy volunteers ( 4 % ; p<0.01 ) . ASA resistance occurred more often in patients with type 2 diabetes , hypertriacylglycerolemia , and decreased HDL levels , and in smokers ( p<0.05 ) . A single assessment of platelet aggregometry was sufficient to identify ASA-resistant patients . During the 4-year follow-up , the patients with ASA resistance had an 88 % incidence of recurrent cardiovascular events versus 46 % for the patients without ASA resistance ( p<0.01 ) . In the subgroup with recurrent cardiovascular ( CV ) events , significantly more patients were ASA-resistant than in the subgroup without recurrent CV events ( 72 % vs. 8 % , p<0.01 ) . CONCLUSION ASA resistance measured by CPG-induced platelet aggregometry is more common among patients with ACS and some metabolic risk factors , and ASA-resistant patients have a significantly higher recurrence of cardiovascular events To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis , the authors studied consecutive patients during a 29-month period . Information regarding their ischemic events , risk factors , and medications was collected . Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin .  A total of 653 patients were evaluated . Of these , 129 patients ( 20 % ) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen , arachidonic acid , or both . A total of 87 ( 13 % ) of the 653 patients were clinical aspirin failures ( ie , presented with new focal cerebral ischemic symptoms while taking aspirin ) . Of the patients with new cerebral ischemic symptoms , 57 ( 66 % ) were determined to be platelet nonresponsive to aspirin . The odds ratio for platelet nonresponsiveness to aspirin  in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 ( 95 % confidence interval : 8.5 - 23.7 ; P < .5 ) . Continued platelet aggregation despite  aspirin treatment occurred in 20 % of ambulatory patients treated for secondary stroke prophylaxis . The prevalence of nonresponsiveness to aspirin  was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin ( P < .5 ) compared with patients who remained without new ischemic symptoms OBJECTIVES This study was design ed to determine if aspirin resistance is associated with clinical events . BACKGROUND Aspirin resistance , defined by platelet function testing and presumed clinical unresponsiveness to aspirin , has been previously reported by our group and others . However , little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events . METHODS We prospect ively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin ( 325 mg/day for > or = 7 days ) and no other antiplatelet agents .  We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate ( ADP ) and arachidonic acid ( AA ) . The primary outcome was the composite of death , myocardial infa rct ion ( MI ) , or cerebrovascular accident ( CVA ) . Mean follow-up was 679 + /- 185 days . Aspirin resistance was defined as a mean aggregation of > or = 70 % with 10 microM ADP and > or = 20 % with 0.5 mg/ml AA . RESULTS Of the patients studied , 17 ( 5.2 % ) were aspirin resistant and 309 ( 94.8 % ) were not aspirin resistant . During follow-up , aspirin resistance was associated with an increased risk of death , MI , or CVA compared with patients who were aspirin sensitive ( 24 % vs. 10 % , hazard ratio [ HR ] 3.12 , 95 % confidence interval [ CI ] 1.10 to 8.90 , p = 0.03 ) . Stratified multivariate analyses identified platelet count , age , heart failure , and aspirin resistance to be independently associated with major adverse long-term outcomes ( HR for aspirin resistance 4.14 , 95 % CI 1.42 to 12.06 , p = 0.009 ) . CONCLUSIONS This study demonstrates the natural history of aspirin resistance in a stable population , documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance Aspirin prevents the production of thromboxane A2 ( TXA2 ) by irreversibly inhibiting platelet cyclooxygenase , exhibiting antiplatelet actions . This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infa rct ion via this action mechanism . However , there are individual differences in this action , and aspirin is not effective in some patients , which is referred to as ‘ aspirin resistance ’ . In this study , we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms ( SNPs ) of nine genes involved in platelet aggregation/hemorrhage . Among SNPs involved in platelet aggregation , aspirin  was less effective for 924 T homozygote of a TXA2 receptor , 924T > C , and 1018C homozygote of a platelet membrane glycoprotein GPIbα , 1018C > T , suggesting that 924 T and 1018C alleles are involved in aspirin resistance Aspirin resistance may increase the risk of major adverse cardiac events ( MACE ) more than threefold in patients with stable coronary artery disease ( CAD ) . This study aim ed to determine the prevalence of aspirin resistance in patients with stable CAD , the role of aspirin resistance on outcome in the follow-up , and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals . We detected the prevalence of aspirin resistance in 234 patients with stable CAD . Platelet function was determined by PFA-100 with collagen and /or epinephrine and collagen and /or ADP cartridges . The mean follow-up time was 20.6 ± 6.9 months . The primary endpoints of the study were occurrence of myocardial infa rct ion , unstable angina , stroke and cardiac death . Of patients , 22.2 % ( n = 52 ) were aspirin resistant by PFA-100 . During follow-up , MACE occurred in eight patients ( 15.4 % ) with aspirin resistance and in 20 patients ( 11.0 % ) with aspirin-sensitive platelet aggregation ( P = 0.269 ) . MACE increased in aspirin-resistant patients after termination of clopidogrel therapy . Eleven patients experienced MACE after cessation of clopidogrel therapy ( P < 0.001 ) . The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100 . The MACE prevalence increased during follow-up , however , just after cessation of clopidogrel therapy OBJECTIVE To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infa rct ion ( AMI ) by use of the Platelet Function Analyzer-100 . INTRODUCTION Previous studies have demonstrated the existence of aspirin resistance , but the clinical relevance of the phenomenon remains to be clarified . If aspirin resistant patients comprise a high-risk subgroup , it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI . We hypothesized that the prevalence of aspirin resistance in patients with AMI was twice the prevalence in patients without AMI . METHODS We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI . All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission .  Platelet function was measured immediately at admission , and aspirin resistance was defined as a collagen/epinephrine Closure Time ( CT(CEPI))<165 s. RESULTS We found that 70 ( 23.5 % ) patients were  aspirin resistant , and 70 ( 23.5 % ) patients ended up with the diagnosis of an AMI . The prevalence of aspirin resistance was significantly higher in patients with AMI as compared to patients without ( 36 % versus 20 % , OR 2.26 , CI 95 % 1.19 - 4.22 , p=0.0058 ) . The CT(CEPI ) measured at admission was an independent factor associated with an AMI . CONCLUSIONS  Aspirin resistance is present in almost one fourth of patients admitted to hospital with symptoms suggestive of an AMI , and aspirin resistance is significantly associated with the diagnosis of a definite AMI We determined the prevalence and clinical predictors of aspirin resistance by prospect ively study ing 325 patients with stable cardiovascular disease who were receiving aspirin ( 325 mg/day for > or = 7 days ) but no other antiplatelet agents .  We also compared the detection of aspirin resistance with optical platelet aggregation , a widely accepted method , with a newer , more rapid method , the platelet function analyzer (PFA)-100 , a whole blood test that measures platelet adhesion and aggregation ex vivo . Blood sample s were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate ( ADP ) and arachidonic acid , and by PFA-100 using collagen and /or epinephrine and collagen and /or ADP cartridges to measure aperture closure time . Aspirin resistance was defined as a mean aggregation of > or = 70 % with 10 microM ADP and a mean aggregation of > or = 20 % with 0.5 mg/ml arachidonic acid . Aspirin semiresponders were defined as meeting one , but not both of the above criteria . Aspirin resistance by PFA-100 was defined as having a normal collagen and /or epinephrine closure time ( < or = 193 seconds ) . By optical aggregation , 5.5 % of the patients were aspirin resistant and 23.8 % were aspirin semiresponders . By PFA-100 , 9.5 % of patients were aspirin resistant . Of the 18 patients who were aspirin resistant by aggregation , 4 were also aspirin resistant by PFA-100 . Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women ( 34.4 % vs 17.3 % , p = 0.001 ) and less likely to be smokers ( 0 % vs 8.3 % , p = 0.004 ) compared with aspirin-sensitive patients . There was a trend toward increased age in patients with aspirin resistance  or aspirin semiresponders ( 65.7 vs 61.3 years , p = 0.06 ) . There were no differences in aspirin sensitivity by race , diabetes , platelet count , renal disease , or liver disease Recently , great interest has focused on the phenomenon of aspirin resistance , which may be defined as clinical or laboratory resistance . Monitoring the antiplatelet effect appears to be relevant in the presence of clinical implication s , but no data are available on the possible clinical implication s of the failure of aspirin to inhibit tests of platelet function in the setting of acute coronary syndromes . This study evaluated the role of aspirin resistance in the occurrence of 1-year major adverse coronary events ( MACEs ) in patients with acute myocardial infa rct ion ( AMI ) who have undergone percutaneous coronary intervention ( PCI ) . We prospect ively evaluated 146 patients ( 115 men and 31 women ; median age 65 years , range 30 to 84 ) with AMI who underwent primary PCI . Exclusion criteria were the use of glycoprotein IIb/IIIa inhibitors , hematocrit < or=30 % , and a platelet count < 100,000/mm3 . Platelet function analyzer-100 closure times by collagen-epinephrine were used for measuring platelet function in venous blood sample s obtained 12 to 15 hours after revascularization . Patients were considered aspirin resistant in the presence of a collagen-epinephrine closure time of < 203 seconds . After 1-year follow-up , MACEs were recorded in 44 of 146 patients ( 30.1 % ) . A significantly higher percentage of patients with MACEs had aspirin resistance ( 39.1 % vs 23.2 % , p < 0.05 ) . A Kaplan-Meier survival curve showed that the overall risk of MACEs was significantly higher among patients with aspirin resistance ( p = 0.02 ) . A Cox regression analysis that adjusted for age , gender , traditional cardiovascular risk factors , systolic left ventricular function , number of stenosed coronary arteries , and previous AMI , PCI , or coronary artery bypass graft showed aspirin resistance to be a significant and independent risk factor for the future MACEs ( hazard ratio 2.9 , 95 % confidence interval 1.1 to 9.2 , p < 0.05 ) . In conclusion , our data demonstrate that aspirin resistance after PCI is a significant and independent predictor of MACEs in patients with AMI undergoing primary PCI BACKGROUND Acetylsalicylic acid , or aspirin , is widely used in secondary prevention of coronary artery diseases , but the inhibition of platelet aggregation is not uniform in all individuals . OBJECTIVE To investigate the prevalence of aspirin resistance at rest and during exercise in coronary artery disease patients . MATERIAL S AND METHODS Fifty patients with stable coronary artery disease were prospect ively studied . All patients received aspirin ( 75 - 300 mg/day for > 1 month ) and no other antiplatelet therapy . Aspirin resistance was studied , at rest and immediately after a stress test , using the st and ardized platelet function analyzer ( PFA-100(R ) , Dade-Behring ) . Aspirin resistance was defined as a normal collagen/epinephrine closure time ( < 186 s ) . RESULTS Ten patients ( 20 % ) were  aspirin-resistant  at rest . Out of the 40 patients who were aspirin-sensitive at rest , 9 ( 22 % ) were aspirin-resistant immediately after the exercise stress test . There were no differences in aspirin sensitivity regarding gender , age , diabetes , hypertension , dyslipidemia , platelet count , medical treatment or number of the coronary arteries involved . CONCLUSIONS Aspirin resistance is detected , at rest , in 20 % of our patients with stable coronary artery disease .  Aspirin treatment does not seem to protect against exercise-induced platelet activation in 22 % of such patients , despite aspirin sensitivity at rest 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 - Abstract Background : Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events ( MACE ) in patients with stable coronary artery disease . Aim : The aim of our study was to determine ; the prevalence of aspirin resistance in patients with acute coronary syndromes , the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects . Material and methods : We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome .  Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 ( Dade Behring , Germany ) with collagen and /or epinephrine ( Col/Epi ) and collagen and /or ADP ( Col/ADP ) cartridges . Primary end points of the study were myocardial infa rct ion , unstable angina , cardiac death . Results : 19 % ( n = 20 ) of patients were aspirin resistant by PFA-100 . In the follow-up , MACE occured in 9 patients ( 45 % ) with aspirin resistance and in 10 patients ( 11.7 % ) with aspirin sensitive platelet aggregation ( p = 0.001 ) . Multivariate analysis showed that aspirin resistance was an independant predictor of MACE . The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months ( p = 0.040 ) . Conclusions : We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance , was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation . Our results showed that aspirin resistance , was an independant predictor of MACE in patients with acute coronary syndrome Previous studies have shown that more complete platelet inhibition improves the coronary flow reserve ( CFR ) , a measure of microvascular integrity , in patients undergoing percutaneous coronary intervention ( PCI ) . We hypothesized that patients with aspirin resistance would have impaired CFR after elective PCI . We used VerifyNow Aspirin to determine the response to aspirin in 117 consecutive patients who underwent elective single-lesion PCI . The assay results are expressed quantitatively in Aspirin Reaction Units based on the degree of platelet aggregation . All patients received a 300-mg loading dose of clopidogrel > 12 hours before and a 75-mg maintenance dose the morning of PCI . CFR was estimated using the Thrombolysis In Myocardial Infa rct ion frame count method . Of the 117 patients , 22 ( 18.8 % ) were aspirin resistant . The clinical , angiographic , and procedural characteristics of the aspirin-sensitive and -resistant patients were balanced . All patients underwent successful PCI with < 50 % residual diameter stenosis and Thrombolysis In Myocardial Infa rct ion grade 3 flow after PCI . Aspirin-resistant patients had a lower CFR than the aspirin-sensitive patients ( 1.42 + /- 0.35 vs 1.80 + /- 0.64 , p = 0.018 ) . Univariate correlates of CFR included the Aspirin Reaction Unit ( r = -0.227 , p = 0.014 ) and post-PCI creatine kinase-MB elevation ( p = 0.048 ) . Multivariate linear regression analysis revealed the Aspirin Reaction Unit to be the only independent determinant of CFR after PCI ( r2 = 0.051 , p = 0.014 ) . Thus , aspirin resistance was associated with impaired CFR in patients who underwent elective PCI , implicating insufficient aspirin-induced platelet inhibition as a cause of microvascular dysfunction by distal atherothrombotic embolization and /or spasm Aspirin , compared with placebo , reduces the risk of cardiovascular events by 25 % in population s of patients with and without known arterial vascular disease . However , the phenomena of ‘ aspirin resistance ’ that has been described in 5–50 % of this population may critically reduce aspirin 's efficacy . One study has suggested that aspirin-resistant patients have a 3.5 times higher risk of cardiovascular death . Presently , there are no established , simple , broadly used methods determining antiplatelet properties of aspirin , while conventional aggregometry requires special equipment and trained personnel . We sought to determine the validity of an Ultegra analyzer with the novel aspirin-sensitive cartridge before and after one pill of non-enteric coated aspirin ( 325 mg ) in subjects with multiple risk factors for coronary artery disease . One hundred and fifty-four volunteers were enrolled into the multicenter study , but six of them were excluded . Data from 148 participants were analyzed . Platelets were assessed twice at baseline ( pre-aspirin ) , and after 2–30 h ( post-aspirin ) . We employed 5 μmol/l epinephrine-induced conventional aggregometry , and aspirin response units stimulated by propyl gallate with the point-of-care Ultegra analyzer . A single pill of aspirin  reduced platelet-rich plasma aggregation from 72 ± 21 % to 25 ± 10 % , and diminished aspirin reduction units from 647 ± 95 to 436 ± 69 . The overall agreement between the two methods was 87 % with 85 % sensitivity for Ultegra and 88 % for platelet aggregation , respectively . The correlation between the two methods was 0.902 . Timely determination of aspirin resistance represents an indispensable application in current medicine . The Ultegra RPFA-ASA analyzer is a novel , fast method that could be used in clinical practice for monitoring efficacy of aspirin , and for triaging the aspirin-resistant population . The clinical implication s of these data need to be proven in r and omized trials BACKGROUND In inhibiting platelet function , aspirin seems to reduce the risk of cerebrovascular accidents , death , and acute coronary events in patients with nonrheumatic atrial fibrillation .  Aspirin given on alternate days might have the advantage of not hindering prostacyclin synthesis . Thus a study was performed to evaluate whether aspirin used in this way might improve the results reported with daily treatment . METHODS To test this hypothesis 285 patients ( age range 40 to 82 years ) with primary atrial fibrillation were r and omly allocated in an open multicenter trial to 3 groups : ( 1 ) group A1 , treated with 125 mg aspirin daily ( n = 104 ) ; ( 2 ) group A2 , treated with 125 mg aspirin on alternate days ( n = 90 ) , ( 3 ) group C ( controls ) , who were not treated with anticoagulants or platelet inhibitors ( n = 91 ) . RESULTS Inclusion took place from January 1990 to July 1994 , and follow-up ended in May 1996 ( range 1 to 62 months ) . Sudden cardiac death in association with heart failure or angina was the most common final event : 4.8 % , 1.1 % , and 6.6 % in groups A1 , A2 , and C , respectively . Both cardiovascular mortality rate and the incidence of main events were reduced , in relative terms , by 80 % ( 1 . 1 % in group A2 vs 6.6 % in group C ) . The differences were smaller between group A1 and C but did not reach statistical significance . The reduction of main cardiovascular events between groups A1 and A2 was statistically significant ( 7.7 % vs 2.2 % = 5.5 % ; 95 % confidence limits 1 % , 11 % ; P < .05 ) . The difference did not reach statistical significance when other end points were analyzed . CONCLUSION In this trial low-dose aspirin given on alternate days seemed to be an efficient intervention in preventing major cardiovascular events . Regarding strokes , however , aspirin was less efficient . Mortality rate in the 3 groups as a whole was associated with heart failure and the development of ischemic heart disease BACKGROUND Aspirin is one of the main therapeutics in prevention of cardiovascular events due to its antiplatelet activity . However , a sufficient inhibition of platelet function by aspirin is not always achieved . This means that the extent of protection from cardiovascular event is limited . Recently , several studies have introduced the concept of residual platelet reactivity during aspirin therapy and suggested that about 40 % of aspirin users may not respond adequately . We sought to determine whether the profile and prevalence of residual platelet reactivity , measured with the platelet function analyzer ( PFA-100 ; Dade/Behring , Marburg , Germany ) device could predict a recurrent cardiovascular event in patients undergoing coronary artery bypass surgery . METHODS A cohort of 202 consecutive patients receiving primary coronary artery bypass surgery during 2004 was prospect ively recruited . All patients postoperatively received regular st and ard daily 100 mg aspirin .  Platelet function was analyzed by the PFA-100 at 30 + /- 6 days after surgery . A PFA100 closure time less than 190 seconds was defined as residual platelet reactivity . Eighty-six patients ( 43 % ) showed residual platelet reactivity . The mean follow-up time was 32 + /- 10 months and was 100 % complete . RESULTS A total of 75 cardiovascular events have been registered . The majority of these events were among patients with residual platelet activity ( p = 0.001 ) . Out of this number , graft failure was documented in 25 patients . The 42-month freedom from major cardiovascular events was significantly better for patients with adequate platelet inhibition ( p = 0.001 ) . At multivariable analysis residual platelet reactivity ( p = 0.012 ) , incomplete revascularization ( p = 0.029 ) , and diabetes ( p = 0.0009 ) were independently associated with occurrence of negative events . CONCLUSIONS Our results demonstrate that high residual platelet reactivity independently correlates with a worst clinical outcome in patients treated by  coronary artery bypass surgery . The PFA-100 point care test could cheaply and simply discover this condition and contribute to improve the outcome of this subset of patients OBJECTIVE This study was conducted to assess the thromboxane ( TX ) dependence of biochemical and functional indexes used to monitor the effect of low-dose aspirin . BACKGROUND Functional assays of the antiplatelet effects of low-dose aspirin variably reflect the TX-dependent component of platelet aggregation . Previous studies of aspirin resistance were typically based on a single determination of platelet aggregation . METHODS We assessed the TXB(2 ) dependence of biochemical and functional indexes , as well as their intersubject and intrasubject variability during administration of the drug and after its withdrawal in 48 healthy volunteers r and omized to receive aspirin 100 mg daily for 1 to 8 weeks . RESULTS Serum TXB(2 ) was uniformly suppressed by 99 % of baseline . Urinary 11-dehydro-TXB(2 ) , arachidonic acid-induced aggregation , and VerifyNow Aspirin  ( Accumetrics Inc. , San Diego , California ) showed stable , incomplete inhibition ( 65 % , 80 % , and 35 % , respectively ) . Adenosine diphosphate- and collagen-induced aggregation was highly variable and poorly affected by aspirin , with an apparent time-dependent reversal . Inhibition of platelet cyclooxygenase activity was nonlinearly related to inhibition of platelet aggregation . Platelet function largely recovered by day 3 post-aspirin , independently of treatment duration . With any functional assay , occasionally " resistant " subjects were found to be " responders " on previous or subsequent determinations . CONCLUSIONS Platelet cyclooxygenase activity , as reflected by serum TXB(2 ) levels , is uniformly and persistently suppressed by low-dose aspirin in healthy subjects . However , the effect of aspirin is variably detected by functional assays , potentially leading to misclassification of " responder " as " resistant " phenotypes owing to poor reproducibility of functional measurements . The nonlinearity of the relationship between inhibition of TX production and inhibition of platelet function has important clinical implication 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
Prevalences widely differ between studies reporting on aspirin resistance .
BACKGROUND The absolute risk of recurrences among patients using aspirin for prevention of cardiovascular events remains high .
Persistent platelet reactivity despite aspirin therapy might explain this in part .
Reported prevalences of this so-called aspirin resistance vary widely , between 0 % and 57 % .
OBJECTIVES The aim of the study was to systematic ally review all available evidence on prevalence of aspirin resistance and to study determinants of reported prevalence .