opces is a bioequivalent , randomized , double blind , multi - centric clinical trial enrolling six centers in five cities of iran . from march 2007 to november 2009 , 442 patients were included in this study . those centers that have the facility and requirements for stenting and also the tendency for research collaboration patients were randomized at least 12 hours before planned pci to receive a 300 mg loading dose of plavix or osvix ( 1:1 ) and followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy before pci and were continued until one and six months in bms and des groups , respectively . the study was approved by the ethical committee of the isfahan cardiovascular research center , a who collaborating center and was registered in the iranian registration clinical trial ( irct138712111723n1 ) . patients were eligible for enrollment if they were  18 years of age , had chronic stable angina and selected for stenting in a coronary artery with diameter  2.5 mm . exclusion criteria included previous treatment with a clopidogrel or warfarin for any reason , history of allergy or any contraindication to clopidogrel , high - risk patients ( e.g. , severe left ventricular dysfunction with ejection fraction less than 30% , stenting of saphenous vein grafts or internal mammary artery ) , total vessel occlusion without myocardial viability in des and large thrombus in angiography before pci . baseline and demo graphic information including sex , age , indications for stenting , morphology , length , and diameter of stent , previous cardiac interventions , and left ventricular ejection fraction based on echocardiography reports were recorded according to the patients medical charts . history of smoking , hypercholesterolemia , hypertriglyceridemia , high blood pressure , diabetes mellitus and family history of premature coronary heart disease ( cad ) in first relatives were also recorded . blood samples were drawn from each patient before the intervention to measure the platelet and neutrophil counts as well as liver enzymes . patients who were selected for stenting were randomly assigned to receive a 300 mg loading dose of plavix ( n = 221 ) or osvix ( n = 221 ) ( 1:1 randomization ratio ) 12 hours before the procedure followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy three days before pci and were continued until one and six months in bms and des groups , respectively . the laboratory assessment was performed for all patients before the study , then one month after pci for patients with bms and one and six months after pci for patients with des . blood samples were taken in one month and six months in bms and des groups to measure platelets , neutrophils , alanine ami - notransferase ( alt ) , and aspartate ami - notransferase ( ast ) . pci was considered successful when a residual diameter stenosis was less than 20% with thrombolysis in myocardial infarction ( timi ) flow less than iii . timi iii means contrast material flows briskly into and clears rapidly from the distal segment or good distal runoff.13 timi grade 3 flows were obtained . type a included lesions with the following characteristics : discrete ( < 10 mm length ) , concentric , readily accessible , non - angulated segment , smooth contour , little or no calcium , less than totally occlusive , not ostial in location , no major side branch involvement , and absence of thrombus . type b included lesions of tubular ( 10 - 20 mm length ) , eccentric , moderate tortuosity of proximal segment  45 , irregular contour , moderate to heavy circulation , total occlusion , ostial location , bifurcation lesion requiring double guide wire , and some thrombus present . type c involved diffuse ( > 20 mm length ) , excessive tortuosity of proximal segment , extremely angu - lated segments (  90 ) , with total occlusion > 3 months old , inability to protect major side braches , and degenerated side branches with friable lesions . mace which is the primary endpoint of this study included death , q wave and non - q wave mi , stroke , target lesion revascularization ( tlr ) , target vascular revascularization ( tvr ) , in - stent thrombosis . cardiovascular death was considered as any death with a cardiovascular cause and included those deaths following a cardiovascular procedure ( for example , pci ) , cardiac arrest , mi , pulmonary embolus , stroke , hemorrhage or death due to unknown cause . non- cardiovascular death was defined as death due to a clearly documented non - cardiovascular cause ( e.g. , trauma , infection , malignancy ) . mi was defined by symptoms suggestive of infarction , electrocardiographic changes , and positive cardiac enzymes . in - stent thrombosis was classified in three groups ; definite : the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion ; probable : unexplained deaths within 30 days after procedure or acute myocardial infarction involving the target - vessel territory without angiographic confirmation ; possible : all unexplained deaths occurring at least 30 days after the procedure . stroke defined as a new focal neurological deficit thought to be vascular in origin with signs and symptoms lasting more than 24 hours . secondary endpoints included changes of platelet or neutrophil number or liver enzymes , hospitalization for angina , and major bleeding . all primary and secondary end points were assessed during hospitalization and after 30 days in bms and six months in des group . the academic research consortium definitions were used for stent thrombosis.14 results were reported as mean  standard deviation ( sd ) for the quantitative variables and percentages for the categorical variables . the groups were compared using the chi - square test ( or fisher 's exact test if required ) for categorical variables and the t - test or mannwhitney u test for the continuous variables . all the statistical analyses were performed using spss version 16.0 ( spss inc . , chicago , il , usa ) for windows . opces is a bioequivalent , randomized , double blind , multi - centric clinical trial enrolling six centers in five cities of iran . from march 2007 to november 2009 , 442 patients were included in this study . those centers that have the facility and requirements for stenting and also the tendency for research collaboration patients were randomized at least 12 hours before planned pci to receive a 300 mg loading dose of plavix or osvix ( 1:1 ) and followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy before pci and were continued until one and six months in bms and des groups , respectively . the study was approved by the ethical committee of the isfahan cardiovascular research center , a who collaborating center and was registered in the iranian registration clinical trial ( irct138712111723n1 ) . patients were eligible for enrollment if they were  18 years of age , had chronic stable angina and selected for stenting in a coronary artery with diameter  2.5 mm . exclusion criteria included previous treatment with a clopidogrel or warfarin for any reason , history of allergy or any contraindication to clopidogrel , high - risk patients ( e.g. , severe left ventricular dysfunction with ejection fraction less than 30% , stenting of saphenous vein grafts or internal mammary artery ) , total vessel occlusion without myocardial viability in des and large thrombus in angiography before pci . baseline and demo graphic information including sex , age , indications for stenting , morphology , length , and diameter of stent , previous cardiac interventions , and left ventricular ejection fraction based on echocardiography reports were recorded according to the patients medical charts . history of smoking , hypercholesterolemia , hypertriglyceridemia , high blood pressure , diabetes mellitus and family history of premature coronary heart disease ( cad ) in first relatives were also recorded . blood samples were drawn from each patient before the intervention to measure the platelet and neutrophil counts as well as liver enzymes . patients who were selected for stenting were randomly assigned to receive a 300 mg loading dose of plavix ( n = 221 ) or osvix ( n = 221 ) ( 1:1 randomization ratio ) 12 hours before the procedure followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy three days before pci and were continued until one and six months in bms and des groups , respectively . the laboratory assessment was performed for all patients before the study , then one month after pci for patients with bms and one and six months after pci for patients with des . blood samples were taken in one month and six months in bms and des groups to measure platelets , neutrophils , alanine ami - notransferase ( alt ) , and aspartate ami - notransferase ( ast ) . pci was considered successful when a residual diameter stenosis was less than 20% with thrombolysis in myocardial infarction ( timi ) flow less than iii . timi iii means contrast material flows briskly into and clears rapidly from the distal segment or good distal runoff.13 timi grade 3 flows were obtained . type a included lesions with the following characteristics : discrete ( < 10 mm length ) , concentric , readily accessible , non - angulated segment , smooth contour , little or no calcium , less than totally occlusive , not ostial in location , no major side branch involvement , and absence of thrombus . type b included lesions of tubular ( 10 - 20 mm length ) , eccentric , moderate tortuosity of proximal segment  45 , irregular contour , moderate to heavy circulation , total occlusion , ostial location , bifurcation lesion requiring double guide wire , and some thrombus present . type c involved diffuse ( > 20 mm length ) , excessive tortuosity of proximal segment , extremely angu - lated segments (  90 ) , with total occlusion > 3 months old , inability to protect major side braches , and degenerated side branches with friable lesions . mace which is the primary endpoint of this study included death , q wave and non - q wave mi , stroke , target lesion revascularization ( tlr ) , target vascular revascularization ( tvr ) , in - stent thrombosis . cardiovascular death was considered as any death with a cardiovascular cause and included those deaths following a cardiovascular procedure ( for example , pci ) , cardiac arrest , mi , pulmonary embolus , stroke , hemorrhage or death due to unknown cause . non- cardiovascular death was defined as death due to a clearly documented non - cardiovascular cause ( e.g. , trauma , infection , malignancy ) . mi was defined by symptoms suggestive of infarction , electrocardiographic changes , and positive cardiac enzymes . in - stent thrombosis was classified in three groups ; definite : the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion ; probable : unexplained deaths within 30 days after procedure or acute myocardial infarction involving the target - vessel territory without angiographic confirmation ; possible : all unexplained deaths occurring at least 30 days after the procedure . stroke defined as a new focal neurological deficit thought to be vascular in origin with signs and symptoms lasting more than 24 hours . secondary endpoints included changes of platelet or neutrophil number or liver enzymes , hospitalization for angina , and major bleeding . all primary and secondary end points were assessed during hospitalization and after 30 days in bms and six months in des group . the academic research consortium definitions were used for stent thrombosis.14 results were reported as mean  standard deviation ( sd ) for the quantitative variables and percentages for the categorical variables . the groups were compared using the chi - square test ( or fisher 's exact test if required ) for categorical variables and the t - test or mannwhitney u test for the continuous variables . all the statistical analyses were performed using spss version 16.0 ( spss inc . , chicago , il , usa ) for windows . opces is a bioequivalent , randomized , double blind , multi - centric clinical trial enrolling six centers in five cities of iran . from march 2007 to november 2009 , 442 patients were included in this study . those centers that have the facility and requirements for stenting and also the tendency for research collaboration patients were randomized at least 12 hours before planned pci to receive a 300 mg loading dose of plavix or osvix ( 1:1 ) and followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy before pci and were continued until one and six months in bms and des groups , respectively . the study was approved by the ethical committee of the isfahan cardiovascular research center , a who collaborating center and was registered in the iranian registration clinical trial ( irct138712111723n1 ) . patients were eligible for enrollment if they were  18 years of age , had chronic stable angina and selected for stenting in a coronary artery with diameter  2.5 mm . exclusion criteria included previous treatment with a clopidogrel or warfarin for any reason , history of allergy or any contraindication to clopidogrel , high - risk patients ( e.g. , severe left ventricular dysfunction with ejection fraction less than 30% , stenting of saphenous vein grafts or internal mammary artery ) , total vessel occlusion without myocardial viability in des and large thrombus in angiography before pci . all the patients underwent complete history and physical examination . baseline and demo graphic information including sex , age , indications for stenting , morphology , length , and diameter of stent , previous cardiac interventions , and left ventricular ejection fraction based on echocardiography reports were recorded according to the patients medical charts . history of smoking , hypercholesterolemia , hypertriglyceridemia , high blood pressure , diabetes mellitus and family history of premature coronary heart disease ( cad ) in first relatives were also recorded . blood samples were drawn from each patient before the intervention to measure the platelet and neutrophil counts as well as liver enzymes . patients who were selected for stenting were randomly assigned to receive a 300 mg loading dose of plavix ( n = 221 ) or osvix ( n = 221 ) ( 1:1 randomization ratio ) 12 hours before the procedure followed by 75 mg / day for 30 days in bms and 6 months in des groups . all patients received daily aspirin therapy three days before pci and were continued until one and six months in bms and des groups , respectively . the laboratory assessment was performed for all patients before the study , then one month after pci for patients with bms and one and six months after pci for patients with des . blood samples were taken in one month and six months in bms and des groups to measure platelets , neutrophils , alanine ami - notransferase ( alt ) , and aspartate ami - notransferase ( ast ) . pci was considered successful when a residual diameter stenosis was less than 20% with thrombolysis in myocardial infarction ( timi ) flow less than iii . timi iii means contrast material flows briskly into and clears rapidly from the distal segment or good distal runoff.13 timi grade 3 flows were obtained . type a included lesions with the following characteristics : discrete ( < 10 mm length ) , concentric , readily accessible , non - angulated segment , smooth contour , little or no calcium , less than totally occlusive , not ostial in location , no major side branch involvement , and absence of thrombus . type b included lesions of tubular ( 10 - 20 mm length ) , eccentric , moderate tortuosity of proximal segment  45 , irregular contour , moderate to heavy circulation , total occlusion , ostial location , bifurcation lesion requiring double guide wire , and some thrombus present . type c involved diffuse ( > 20 mm length ) , excessive tortuosity of proximal segment , extremely angu - lated segments (  90 ) , with total occlusion > 3 months old , inability to protect major side braches , and degenerated side branches with friable lesions . mace which is the primary endpoint of this study included death , q wave and non - q wave mi , stroke , target lesion revascularization ( tlr ) , target vascular revascularization ( tvr ) , in - stent thrombosis . cardiovascular death was considered as any death with a cardiovascular cause and included those deaths following a cardiovascular procedure ( for example , pci ) , cardiac arrest , mi , pulmonary embolus , stroke , hemorrhage or death due to unknown cause . non- cardiovascular death was defined as death due to a clearly documented non - cardiovascular cause ( e.g. , trauma , infection , malignancy ) . mi was defined by symptoms suggestive of infarction , electrocardiographic changes , and positive cardiac enzymes . in - stent thrombosis was classified in three groups ; definite : the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion ; probable : unexplained deaths within 30 days after procedure or acute myocardial infarction involving the target - vessel territory without angiographic confirmation ; possible : all unexplained deaths occurring at least 30 days after the procedure . stroke defined as a new focal neurological deficit thought to be vascular in origin with signs and symptoms lasting more than 24 hours . secondary endpoints included changes of platelet or neutrophil number or liver enzymes , hospitalization for angina , and major bleeding . all primary and secondary end points were assessed during hospitalization and after 30 days in bms and six months in des group . results were reported as mean  standard deviation ( sd ) for the quantitative variables and percentages for the categorical variables . the groups were compared using the chi - square test ( or fisher 's exact test if required ) for categorical variables and the t - test or mannwhitney u test for the continuous variables . all the statistical analyses were performed using spss version 16.0 ( spss inc . , chicago , il , usa ) for windows . the total study population represents a group of 442 patients ( mean age 59  9.5 years ) with stable angina pectoris in whom pci was performed . among them , 225 participants implanted bms and the rest implanted des . a total of 224 patients treated with osvix ( 110 patients in bms and 114 patients in des ) and 218 subjects were treated with plavix ( 115 patients in bms and 103 patients in des ) . except male to female ratio that was higher in the osvix than the plavix group , the two drug groups were comparable with respect to baseline characteristics , clinical data especially left ventricular ejection fraction , and medical history . there were significantly more frequent hypertensive patients in the osvix than in the plavix group ( p < 0.01 ) , but no other significant differences were seen in patient characteristics between the two groups table 2 . besides , in both groups with des and bms , there was no significant difference in the type of coronary lesion , direct stenting , stent length and stent diameter ( table 3 ) . baseline characteristics and clinical data of all participants based on plavix or osvix use recorded characteristics and clinical data of all patients based on their stent type . coronary angiography and stent characteristics of patients and drug type used figure 1 shows the frequency and 95% confidence intervals of events such as death , instant thrombosis , mace rate , and mi following osvix or plavix placement in bare - metal or drug eluting stents patients . frequency and 95% confidence intervals of events following osvix or plavix placement in bare - metal or drug eluting stents patients there was no significant difference regarding mace rate in patients treated with osvix compared with plavix ( figure 1 ) . the study groups had the same frequency of mi , thrombosis , stroke and tvr ( figure 1 ) . regarding changes in laboratory variable , no significant changes were found concerning liver enzymes , platelet and neutrophil counts between the two drug regimens in both des and bms groups ( figures 2 and 3 ) . changes of serum platelet and neutrophil counts following osvix and plavix regimens in patients who underwent bare - metal or drug eluting stenting changes of serum aspartate aminotransferase and alanine aminotransferase levels following osvix and plavix regimens in patients who underwent bare - metal or drug eluting stenting opcess is the first randomized trial to compare the effect of a generic form of clopidogrel on mace after coronary stenting in iran . increased platelet activity has been shown to increase cardiovascular complications in acute coronary syndrome ( acs ) , and subsequent to pci.15 various studies have demonstrated that administration of antiplatelet drugs such as aspirin , ticlopidine and clopidogrel reduce short and long - term cardiovascular events in patients suffering acs or undergoing pci.16 we studied the short and long - term cardiovascular complications , including death , myocardial infarction , stroke , tlr and tvr in patients treated with osvix ( 300 mg bolus , and 75 mg / daily maintenance ) or plavix ( 300 mg bolus , and 75 mg / daily maintenance ) . assessment of secondary end - points such as angina , heart failure ( hf ) , major hemorrhagic episodes , and reduction of platelet or neutrophil counts and liver enzyme changes revealed no significant difference between the two treated groups . reduced systolic performance and ageing are among important factors underlying mace in these patients . however , the frequency distribution of age , sex and left ventricular systolic function were similar in osvix and plavix groups . tavazzi showed that concomitant disease and cvd risk factors can increase mace.17 whereas these risk factors were evenly distributed in the two groups in this randomized clinical trial ; a higher frequency of hypertension in the osvix group was seen ( p = 0.001 ) ( table 2 ) . kang and colleagues demonstrated that hypertension does not affect short and long - term cardiovascular complications of pci.18 patients in osvix group showed nonsignificant lower mace rate than the plavix group ( p < 0.05 ) . thus , it can be concluded that osvix has at least similar cvd complications as plavix . ali - doosti and colleagues showed that the type of vessel selected for pci did not affect the short and long term complications of the procedure.19 in our study , the frequency distribution according to the vessel elected for angioplasty was the same in both groups . various studies have demonstrated an increase in short and long term post - angioplasty complications in patients with complex lesions : the worse the anatomy and morphology of the lesion , the more difficult the procedure and the poorer the outcomes.2021 in our study , the frequency distribution of the type of coronary lesion elected for angioplasty was not significantly different in the osvix and plavix groups . in separate studies , singh and pompa showed that the length and diameter of stents are directly , and inversely proportional to tlr.2223 in our study , the stent length and diameter , as well as angioplasty technique had similar distribution in both groups , although the rate of tvr was low in our study as shown by results . this may have been due to the short follow - up period ( one month for non - pharmacological stents and six months for pharmacological stents ) . tvr was seen in two of our patients who underwent cabg a day after unsuccessful angioplasty . based on comparison of frequency distribution of patients according to mace in the preceding one and six months for bms and des stents , respectively , the incidence of mace including death was similar in the osvix and plavix groups . the incidence of mi was 0.4% in the osvix and 1.4% in the pla - vix groups with no significant difference . no significant difference was observed between the two groups in regard to episodes of angina , hf and bleeding which suggest no inferiority of osvix compared to plavix . although the occurrence of events was not significantly different in the two groups , the distribution of findings revealed an up - sloping trend in complications in the plavix group . thus , it may be concluded that osvix was not associated with more complications than plavix in patients who underwent pci . safety of antiplatelet drugs is of great importance and must be assessed against possible side - effects . gurbel demonstrated that including clopidogrel in the therapy of unstable angina patients , significantly reduced mortality from mace . although clopidogrel may significantly increase the risk of bleeding , its benefits have been shown to outweigh the risks.24 yusuf and colleagues showed that adding clopidogrel to aspirin reduced mace but increased the risk of bleeding . however , in our study , the rate of major bleeding in osvix and plavix groups who were treated with aspirin too , were not significant . during our follow - up period , mean platelet counts did not change significantly in either groups ( plavix , p = 0.80 and osvix , p = 0.99 ) or between them ( p = 0.87 ) . however , neutrophil counts were reduced significantly in the two groups ( p < 0.001 ) , but the trend of change in counts was not significantly different between the two groups . the above findings showed that adverse hematological effects ( thrombopenia or neutropenia ) did not increase in the osvix group as compared to the plavix group . we noted some limitations to our study , the most important of which was the small study population . however , the power of the study was enough to achieve the main and secondary objectives of the study . the other important limitation was that the angiographies were performed by different cardiologists in different centers . thus , interobserver variability was inevitable . in conclusion , our data demonstrated the safety of osvix in improving clinical outcome compared to plavix after coronary stenting in bms or des using patients . the frequency of mace , non - cardiac events or adverse hematological changes did not increase with osvix compared to plavix patients which suggest it 's safety . however , due to more cost advantages of osvix regimen over plavix , administration of osvix among iranian patients is preferable . akh designed the study and drafted this manuscript , mp designed the study , mo , gkm , mn , akh , mh , fr , shs , and jk carried the study , mgh drafted the manuscript and tables , hz helped in designing the study and carried the study , aat helped in designing the study , bs data analysis and drafted the tables , mgh helped in designing the study , mrkh and fn helped in statistical analysis , ekh and mj helped in data gathering , and ns helped in designing the study , revising the manuscript procedures , and drafting the manuscript .
background : to compare the early and late cardiovascular events as well as side effects of osvix , a generic form of clopidogrel versus plavix regimens in patients with chronic stable angina , undergoing bare metal stent ( bms ) or drug eluting stent ( des ) placement , this study was carried out.methods:a total of 442 patients with chronic stable angina who were scheduled for elective percutaneous coronary intervention ( pci ) were included in a randomized , double blind , multi - centric clinical trial being performed in 6 distinct university hospitals in 5 cities of iran from march 2007 to november 2009 . 
 baseline , demographic and history of risk factors were recorded using the patients medical charts . 
 stenting procedure was performed via transfemoral approach using low osmolar contrast agents . 
 patients underwent bms or des placements based on the physician selection and were randomly assigned to osvix or plavix groups . 
 patients were followed by telephone in 0 and 6 months intervals regarding the major adverse cardiovascular events ( mace ) including death , myocardial infarction , in - stent thrombosis , stroke , target lesion revascularization , and target vascular revascularization . 
 angina episodes , bleeding , liver enzymes , neutrophils and platelets count were also assessed in these intervals.results:there was not any significant difference between these two groups regarding the baseline characteristics . in the des group , 
 the 6-month mortality rate and the incidence of mace in osvix and plavix groups were 0.9% and 1.9% ( p = 0.61 ) and 1.8% and 4.9% ( p = 0.26 ) , respectively . during the follow up period after des or bms placement , there was nt any significant difference regarding neutrophil and platelet counts or liver enzymes between study groups.conclusions:using osvix and plavix are followed by similar major cardiovascular events and side - effect profile in patients undergoing pci .