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Clopidogrel
Selected AbstractsIncreased Mortality Associated With Low Use of Clopidogrel in Patients With Heart Failure and Acute Myocardial Infarction Not Undergoing Percutaneous Coronary InterventionCONGESTIVE HEART FAILURE, Issue 5 2010Scott Harris DO We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI). Background. Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel is associated with absolute mortality reduction in AMI patients. Methods. All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan,Meier method and Cox regression analyses. Results. We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n=5050) and a mean follow-up of 1.50 years (SD=1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively (P=.002). The corresponding numbers for patients without HF (n=6092), with a mean follow-up of 2.05 years (SD=1.3), were 285 (9.4%) and 294 (9.7%), respectively (P=.83). Patients with HF receiving clopidogrel demonstrated reduced mortality (hazard ratio, 0.86; 95% confidence interval, 0.78,0.95) compared with patients with HF not receiving clopidogrel. No difference was observed among patients without HF (hazard ratio, 0.98; 95% confidence interval, 0.83,1.16). Conclusions. Clopidogrel was associated with reduced mortality in patients with HF who do not undergo PCI after their first-time AMI, whereas this association was not apparent in patients without HF. Further studies of the benefit of clopidogrel in patients with HF and AMI are warranted.,Bonde L, Sorensen R, Fosbol EL, et al. Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention: a nationwide study. J Am Coll Cardiol. 2010;55:1300,1307. [source] Effects of Clopidogrel and Aspirin Combination vs.CONGESTIVE HEART FAILURE, Issue 1 2004Aspirin Alone on Platelet Aggregation, Major Receptor Expression in Patients With Heart Failure: The Plavix Use for Treatment of Congestive Heart Failure (PLUTO-CHF) Trial No abstract is available for this article. [source] Prevention of secondary stroke and transient ischaemic attack with antiplatelet therapy: the role of the primary care physician roleINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2007H. S. Kirshner Summary Background:, Stroke risk is heightened among patients who have had a primary stroke or transient ischaemic attack (TIA). The primary care physician is in the best position to monitor these patients for stroke recurrence. Because stroke recurrence can occur shortly after the primary event, guidelines recommend initiating antiplatelet therapy as soon as possible. Aspirin, with or without extended-release dipyridamole (ER-DP), and clopidogrel are options for such patients. Low-dose aspirin (75,150 mg/day) has the same efficacy as higher doses but with less gastrointestinal bleeding. Clopidogrel remains an option for prevention of secondary events and may benefit patients with symptomatic atherothrombosis, but its combined use with aspirin can harm patients with multiple risk factors and no history of symptomatic cerebrovascular, cardiovascular or peripheral vascular disease. Results:, Low dose aspirin is effective in secondary stroke prevention. Trials assessing aspirin plus ER-DP have shown that the combination is more effective than aspirin monotherapy in preventing stroke, with efficacy increasing among higher risk patients, notably those with prior stroke/TIA. Clopidogrel does not appear to have as much advantage over aspirin in secondary stroke prevention as aspirin plus ER-DP. Smoking cessation and cholesterol, blood glucose and blood pressure control are also important concerns in preventing recurrent stroke. In choosing pharmacological therapy, the physician must consider the individual patient's risk factors and tolerance, as well as other issues, such as use of aspirin among patients with ulcers. Conclusion:, Antiplatelet therapy is effective in secondary stroke prevention. Low dose aspirin can be used first-line, but aspirin plus ER-DP improves efficacy. Clopidogrel is another option in secondary stroke prevention, especially for aspirin-intolerant patients, but it appears to have less advantage over aspirin than aspirin plus ER-DP, and its combined use with aspirin has only marginally better efficacy and increased bleeding risk. [source] Berend Houwen Memorial Lecture: ISLH Las Vegas May 2009INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2009The pathogenesis, management of thrombotic microangiopathies Summary Thrombotic microangiopathies are a relatively rare group of congenital and inherited disorders caused by defects in processing the ultra large forms of von Willibrand factor which pathologically give rise to platelet rich microthrombi in the micro arterial circulation leading to end organ damage particularly in the brain, heart and kidneys. Identification of the ADAMTS 13 gene has led to the definition of congenital deficiency of its activity or failure of activity due to the development of an inhibitory IgG antibody. The idiopathic autoimmune form of the disease is the most common. There are various subgroups of acquired TTP associated with HIV infection, pregnancy, pancreatitis, associated with bone marrow transplantation, various disseminated malignancies and certain drugs, particularly Clopidogrel. Diagnostic assays are now becoming widely available to identify ADAMTS 13 activity and also acquired antibodies to the enzyme. Mainline treatment is associated with daily plasma exchange with associated other immunosuppressant treatments particularly steroids and recently the use of Rituximab, a monoclonal anti-CD20 antibody. Despite improvement in treatment modalities there is still significant mortality of 10,20%, particularly if there is a delay in initiating plasma exchange. Relapse also occurs in 20,50% of patients although this may be improved by Rituximab therapy. [source] Highly Efficient Chemoenzymatic Synthesis of Methyl (R)- o -Chloromandelate, a Key Intermediate for Clopidogrel, via Asymmetric Reduction with Recombinant Escherichia coliADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2008Tadashi Ema Abstract Methyl (R)- o -chloromandelate [(R)- 1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o -chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178,g/L was attained at 20,°C on a 2-g scale (1.0,M). The optimized reaction could be scaled up easily to transform 20,g of 2 in 100,mL of buffer. Three synthetic methods for 2 are compared. [source] Regular or "Super-Aspirins"?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2001A Review of Thienopyridines or Aspirin to Prevent Stroke PURPOSE: To review the evidence for the effectiveness and safety of the thienopyridines (ticlopidine and clopidogrel) compared with aspirin for the prevention of vascular events among patients at high risk of vascular disease. BACKGROUND: Atherosclerosis and resultant cardiovascular disease are important causes of morbidity and mortality in older people. In particular, atherosclerosis of the cerebral arteries can lead to transient ischemic attacks (TIAs) and stroke. Stroke ranks as the third-leading cause of death in the United States and in 1997 was responsible for over 150,000 fatalities.1 In addition to the mortality associated with this disease, stroke is also a leading source of long-term disability in survivors. Nearly 4.5 million stroke survivors are alive today,1 highlighting the fact that primary, but also secondary, prevention are extremely important for minimizing the complications of this illness. DATA SOURCES: Specialized trial registers of the Cochrane Stroke Group and the Antithrombotic Trialist's Collaboration, MEDLINE, and Embase were searched. Additional unpublished information and data were sought from Sanofi, the pharmaceutical company that developed and manufactures ticlopidine and clopidogrel, as well as the principal investigators of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial,7 the largest of the trials identified. STUDY SELECTION CRITERIA: All unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin among patients at high risk of vascular disease (those with symptoms of ischemia of the cerebral, coronary, or peripheral circulations) who were followed for at least 1 month for the recurrence of vascular events were included. DATA EXTRACTION: Data were extracted from four completed randomized trials completed in the past 20 years, which included 22,656 patients.7,10 Two authors independently extracted the data from these trials for the following information: the types of patients enrolled; the entry and exclusion criteria; the randomization method; the number of patients originally allocated to the treatment and control groups; the method and duration of follow-up; the number of patients in each group lost to follow-up; information on compliance with the treatment allocated; the definitions of outcome events; the number of outcome events in each treatment group; and any method used for blinding patients, treating clinicians, and outcome assessors to treatment allocation. MAIN RESULTS: Four completed trials involving a total of 22,656 patients were identified. Aspirin was compared with ticlopidine in three trials (3,471 patients)8,10 and with clopidogrel in one trial (19,185 patients).7 A recent TIA or ischemic stroke was the qualifying event in 9,840 patients, a recent myocardial infarction in 6,302 patients, and symptomatic peripheral arterial disease in 6,514 patients. The average age of the patients was approximately 63, with approximately two-thirds of the patients being male and white. The duration of follow-up ranged from 12 to 40 months. CONCLUSIONS: This systematic review demonstrates that, compared with aspirin, thienopyridines are only modestly more effective in preventing serious vascular events in high-risk patients. For patients who are intolerant of, or allergic to aspirin, the available safety and efficacy data suggest that clopidogrel is an appropriate, but more-expensive, alternative antiplatelet drug. It appears safer than ticlopidine and as safe as aspirin but it should not replace aspirin as the first-choice antiplatelet agent for all patients. Further studies are necessary to determine which, if any, particular types of patients would benefit most and least from clopidogrel instead of aspirin. [source] Smoking behaviour modulates pharmacokinetics of orally administered clopidogrelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008A.-M. Yousef PhD Summary Background and objectives:, Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. Methods:, Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0,,). Results:, One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC0,, (smokers: 6·24 ± 2·32 ,g/h/mL vs. non-smokers: 8·93 ± 3·80 ,g/h/mL, P < 0·001) and shorter half-life (smokers: 5·46 ± 2·99 vs. non-smokers: 8·43 ± 4·26, P = 0·001). Smoking behaviour had no influence on Cmax (P = 0·3) and Tmax (P = 0·7). There was no statistically significant difference in Cmax, AUC0,,, Tmax and t1/2e between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean ± SE; 26·93 ± 0·16 vs. 23·11 ± 0·27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (Cmax = 3·09 ± 0·99 ,g/mL, CV = 32%), (Tmax =0·76 ± 0·24 h, CV = 31·6%), (AUC0,, = 7·98 ± 3·58 ,g/h/mL, CV = 44·8%), and (t1/2e = 7·38 ± 4·10 h, CV = 55·6%). Conclusion:, Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed. [source] Development and Validation of a Risk Scoring Model to Predict Net Adverse Cardiovascular Outcomes after Primary Percutaneous Coronary Intervention in Patients Pretreated with 600 mg Clopidogrel: Rationale and Design of the RISK-PCI StudyJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009IGOR MRDOVIC M.D., Ph.D Background: No comprehensive primary PCI (pPCI) risk model to predict net adverse cardiovascular events (NACE) has been reported with the use of clopidogrel 600 mg, which is now considered the standard loading dose. The primary hypothesis of the RISK-PCI trial is that an accurate risk prediction may be achieved by using clinical, angiographic, and procedural variables available at the time of intervention. Methods: The present single-center, longitudinal, cohort study will include 1,750 consecutive patients with ST-elevation myocardial infarction (STEMI), undergoing pPCI after pretreatment with 300 mg aspirin and 600 mg clopidogrel. The primary end-points of the trial (NACE) include major adverse cardiovascular events (MACE) and major bleeding. A logistic regression model will be developed to predict 30-day and 1-year NACE after pPCI. A risk score derived from study set data will be validated using validation set data. Results: Until June 1, 2008, 1,166 patients have been enrolled. Thirty-day follow-up is available in 1,007 patients. Conclusions: The RISK-PCI study is designed to develop an accurate risk scoring system, using variables available at the time of intervention, to predict long-term adverse outcomes after pPCI. Trial Registration: Current Controlled Trials Register,ISRCTN83474650,http://www.controlled-trials.com/ISRCTN83474650). [source] Crushed Clopidogrel Administered via Nasogastric Tube Has Faster and Greater Absorption than Oral Whole TabletsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009M. UROOJ ZAFAR M.B.B.S. Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers. Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading. Methods: Nine healthy human subjects (34.7 ± 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following ,2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points. Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28,0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84,1.32, P = 0.646). Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated. [source] Ambulatory Use of Ticlopidine and Clopidogrel in Association with Percutaneous Coronary Revascularization Procedures in a National Managed Care OrganizationJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2002DEBORAH SHATIN PH.D. The aim of this study was to quantify ambulatory use of ticlopidine and clopidogrel in association -with percutaneous coronary revascularization procedures (PTCA, atherectomy, stent) in a national managed care organization. Retrospective administrative claims data over a 3-year period (1996,1998) from 12 UnitedHealth Group-affiliated health plans in four geographic regions were collected. Pharmacy and medical claims data were used to determine the patients exposed to ticlopidine and clopidogrel between January 1, 1996 and December 31, 1998, the duration of use, prescriptions within 2 weeks of a coronary procedure, and stent patients prescribed either drug within 2 weeks of stent placement in 1998. Substantial short-term use of ticlopidine and clopidogrel was found. The percentage of members with duration of use , 30 days ranged from 50.4% in 1996 to 56.9% in 1998 for ticlopidine and was 52.7% for clopidogrel. In 1998, 46% and 33% of ticlopidine and clopidogrel users, respectively, had a medical claim for a coronary procedure that fell within 2 weeks of a prescription. The rate was lower for Medicare beneficiaries. In 1998, 78% of stent patients filled a prescription for either drug within 2 weeks of stent implantation. Although little difference was found overall in the use of these agents across geographic regions, a higher proportion of stent patients in the Southeast were prescribed ticlopidine within this timeframe. The findings suggest that during the study time period ticlopidine and clopidogrel are frequently used off-label in association with percutaneous coronary revascularization procedures. These results were important in considering the overall benefit-risk profile. [source] A randomized, placebo-controlled study of the effects of naproxen, aspirin, celecoxib or clopidogrel on gastroduodenal mucosal healingALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009A. DIKMAN Summary Background, Many individuals with gastroduodenal ulcers require on-going, non-steroidal anti-inflammatory drug (NSAID) or anti-platelet therapy. Aims, To evaluate the effects of these agents on gastroduodenal mucosal healing. Methods,Helicobacter pylori -negative volunteers were randomized to receive naproxen, celecoxib, aspirin, clopidogrel or placebo. Antral and duodenal lesions were created endoscopically with a biopsy forceps. After 7 days of medication dosing, each lesion was scored [from 0 (low) to 8 (high)] using a validated methodology. The primary endpoint was the mean injury score. The secondary endpoint was the percentage of subjects with ,1 unhealed lesion. Results, In all, 108 subjects completed the study. Naproxen impaired antral lesion healing more than placebo, clopidogrel, aspirin or celecoxib (mean injury score of 4.3 vs. 3.0, 2.7, 3.2, and 3.2, respectively, P < 0.05). Naproxen impaired duodenal lesion healing more than placebo, clopidogrel or aspirin (mean injury score of 4.0 vs. 2.4, 2.6, and 2.2, respectively, P < 0.05). More subjects taking naproxen than placebo or clopidogrel had ,1 unhealed antral lesions (72.2% vs. 36.0% and 32.0%, respectively, P < 0.05) and unhealed duodenal lesions (61.1% vs. 16.0% and 28.0%, respectively, P < 0.05). Conclusions, Naproxen may impair gastroduodenal healing more than aspirin or celecoxib in H. pylori negative subjects. Clopidogrel did not impair mucosal healing. [source] Optimale individualisierte antithrombozytäre Therapie.PHARMAZIE IN UNSERER ZEIT (PHARMUZ), Issue 4 2009Nach koronarer Stentimplantation Zusammenfassend ist die optimale therapeutische Strategie für Patienten nach koronarer Stentimplantation komplex und benötigt einen zunehmend individuellen Ansatz. Hinzu kommt das Problem des unzureichenden Ansprechens mancher Patienten auf Clopidogrel, Alter, Komorbiditäten, Patienten- Compliance etc. Obwohl wir versucht haben, einen Algorithmus zu definieren, der für die meisten Patienten geeignet ist, muss das individuelle Risikoprofil jedes einzelnen Patienten berücksichtigt werden, bevor eine koronare Intervention bei diesem Hochrisiko-Kollektiv durchgeführt wird. Ein wichtiger Aspekt ist z.B. die Tatsache, dass ein erhöhtes Alter einen Risikofaktor sowohl für eine Stentthrombose als auch für thrombembolische Komplikationen, z.B. bei Vorhofflimmern, und für lebensbedrohliche Blutungskomplikationen darstellt. [source] Clopidogrel and platelet transfusion in patients undergoing coronary artery bypass graft surgery,ANAESTHESIA, Issue 6 2003E. G. Pivalizza No abstract is available for this article. [source] The management of patients with hip fractures who are taking ClopidogrelAUSTRALASIAN JOURNAL ON AGEING, Issue 4 2009Welkee Sim Aim:, To assess the outcomes of patients with acute proximal hip fractures who were taking Clopidogrel. Method:, A retrospective study of 135 patients with proximal hip fractures. Demographic data and clinical outcomes were collected via review of hospital medical records. Results:, 21 patients taking Clopidogrel on admission were compared with 114 patients not on Clopidogrel. The groups were similar in their baseline characteristics. Postoperative haemoglobin and wound haematoma, hospital length of stay and death rate were similar in both groups even when the patients on Clopidogrel were operated on within 2 days of fracture. Days to surgery were longer in the Clopidogrel group than the control group (3.5 vs 0.9). Conclusions:, This study demonstrated that patients on Clopidogrel do not have a worse outcome than those who were not taking the medication. We feel that it is safe to perform surgery as soon as possible. [source] Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug-drug interaction studiesBIOMEDICAL CHROMATOGRAPHY, Issue 3 2009Ramesh Mullangi No abstract is available for this article. [source] Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug,drug interaction studiesBIOMEDICAL CHROMATOGRAPHY, Issue 1 2009Ramesh Mullangi Abstract Clopidogrel, owing to its excellent inhibitory property of platelet aggregation, is used to reduce the cardiovascular risks in patients with multiple co-morbid conditions such as stroke, myocardial infarction and atherosclerosis. The current review focuses distinctly on three aspects: (a) an in-depth coverage on the bioanalytical methods for the quantification of clopidogrel and its inactive carboxylic acid metabolite as well as the active metabolite in pre-clinical and clinical samples; (b) an overview of the pharmacokinetic/pharmacodynamic aspects of clopidogrel; and (c) enumerating the key findings from drug,drug interaction studies of clopidogrel with various co-substrates such as lanzoprazole, fluvastatin, atorvastatin, pravastatin, digoxin, ketoconazole, donezepil and theophylline. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pharmacogenetics Testing: Implications for Cardiovascular Therapeutics with Clopidogrel and WarfarinCARDIOVASCULAR THERAPEUTICS, Issue 3 2010Jacob George First page of article [source] Clopidogrel: mechanisms of action and review of the evidence relating to use during skin surgery proceduresCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2010L. C. Stewart Summary Patients who have skin surgery may be taking medication that increases the likelihood of bleeding, such as clopidogrel, aspirin, warfarin, heparin and nonsteroidal anti-inflammatory drugs (NSAIDS). All of these may increase the risk of perioperative and postoperative bleeding. This article examines the mechanism of action of clopidogrel, current practice, and evidence for or against continuing its use during skin surgery. The mechanisms of action of aspirin, warfarin, heparin and NSAIDS will also be briefly discussed. [source] Antiplatelet Strategies: Evaluating Their Current Role in the Setting of Acute Coronary SyndromesCLINICAL CARDIOLOGY, Issue S1 2008Eugene Braunwald Abstract Numerous clinical trials have established the value of antiplatelet therapies for acute coronary syndromes (ACS). Aspirin (ASA), thienopyridines (i.e., clopidogrel and ticlopidine) and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS and for the prevention of thrombotic complications of percutaneous coronary intervention (PCI). Clopidogrel is beneficial when administered before and after PCI, and is more effective when combined with either ASA or GP IIb/IIIa inhibitors in preventing post-PCI complications, coronary subacute stent thrombosis, and thrombotic events in general. It is currently unclear whether a higher loading dose of clopidogrel (600 mg) is better than the standard loading dose (300 mg), how long therapy should continue, and which maintenance dose is optimal. The role of the GP IIb/IIIa antagonists in ACS is less clear due to conflicting data from several studies with different patient populations. Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high-risk ACS patients scheduled to undergo PCI, who demonstrate non-ST-segment elevation myocardial infarction and elevated troponin levels. Copyright © 2008 Wiley Periodicals, Inc. [source] Clopidogrel versus low-dose aspirin as risk factors for epistaxisCLINICAL OTOLARYNGOLOGY, Issue 3 2009J.W. Rainsbury Objectives:, To quantify the relative risk of epistaxis for patients taking low-dose aspirin or clopidogrel compared to patients taking neither drug. Design:, Case-control study. Setting:, Primary care. Participants:, 10,241 patients from three GP practices in the West Midlands. Main outcome measures:, Epistaxis resulting in presentation to the GP, attendance at Accident & Emergency, or referral to ENT outpatients. Results:, There was a significant difference in the proportion of patients with epistaxis across the three groups (,2 = 84.1; 2 degrees of freedom; P < 0.000001). Relative risk of epistaxis was increased in both the aspirin (RR = 9.04; 95% CI = 5.13,15.96) and clopidogrel (RR = 6.40; 95% CI = 2.33,17.56) groups compared to the no drug group. There was no increased risk of epistaxis with aspirin compared to clopidogrel (RR = 1.4; 95% CI = 0.6,3.4). Conclusion:, There is an increased risk of troublesome epistaxis in patients taking aspirin or clopidogrel. There is no significant difference in risk of epistaxis between the two drug groups. [source] Bleeding risk with AZD6140, a reversible P2Y12 receptor antagonist, vs. clopidogrel in patients undergoing coronary artery bypass grafting in the DISPERSE2 trialINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2009S. Husted Summary AZD6140, the first reversible oral P2Y12 receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped , 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y12 receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects. [source] Increased Mortality Associated With Low Use of Clopidogrel in Patients With Heart Failure and Acute Myocardial Infarction Not Undergoing Percutaneous Coronary InterventionCONGESTIVE HEART FAILURE, Issue 5 2010Scott Harris DO We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI). Background. Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel is associated with absolute mortality reduction in AMI patients. Methods. All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan,Meier method and Cox regression analyses. Results. We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n=5050) and a mean follow-up of 1.50 years (SD=1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively (P=.002). The corresponding numbers for patients without HF (n=6092), with a mean follow-up of 2.05 years (SD=1.3), were 285 (9.4%) and 294 (9.7%), respectively (P=.83). Patients with HF receiving clopidogrel demonstrated reduced mortality (hazard ratio, 0.86; 95% confidence interval, 0.78,0.95) compared with patients with HF not receiving clopidogrel. No difference was observed among patients without HF (hazard ratio, 0.98; 95% confidence interval, 0.83,1.16). Conclusions. Clopidogrel was associated with reduced mortality in patients with HF who do not undergo PCI after their first-time AMI, whereas this association was not apparent in patients without HF. Further studies of the benefit of clopidogrel in patients with HF and AMI are warranted.,Bonde L, Sorensen R, Fosbol EL, et al. Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention: a nationwide study. J Am Coll Cardiol. 2010;55:1300,1307. [source] SPONTANEOUS COLONIC HEMATOMA: ENDOSCOPIC APPEARANCEDIGESTIVE ENDOSCOPY, Issue 2 2007Marcus Martins Dos Santos Intramural colonic hematoma is a rare complication of anticoagulation therapy. We report a patient under therapy with acetylsalicylic acid, low-molecular-weight heparin and clopidogrel for unstable angina, who presented with massive lower gastrointestinal bleeding secondary to spontaneous intramural colonic hematoma, with unremarkable coagulation tests. Diagnosis was promptly made by colonoscopy, and the patient was successfully managed with a conservative approach, with complete resolution of symptoms after 7 days. This is the first report of spontaneous intramural colonic hematoma presumed to be related to acetylsalicylic acid, enoxaparin and clopidogrel. [source] Aggressive chronic platelet inhibition with prasugrel and increased cancer risks: revising oral antiplatelet regimens?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2009Victor L. Serebruany Abstract The TRITON-TIMI 38 was a head-to-head trial to assess the efficacy and safety of the experimental antiplatelet agent prasugrel vs. standard care with clopidogrel on top of aspirin. Besides some ischemic protection at expense of overwhelming bleeding disadvantage, prasugrel treated patients experienced three times higher rate of colonic neoplasms then after clopidogrel, and this difference was significant. Importantly, known gastrointestinal bleeding preceded the diagnosis of colonic neoplasms only in half of the patients. Three potential mechanisms responsible for such harmful association are reviewed, namely: (i) direct hazard of the experimental drug on cancer occurrence and progression; (ii) indirect modulation of tumor growth; and (iii) enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates, or/and inability to keep the disease locally due by much more potent long-term platelet inhibition should be considered. Significant excess of cancer after prasugrel is alarming, and can be reasonably explained, with critical clinical implications not only for prasugrel further development, but also for existing and future chronic antiplatelet strategies. If the hypothesis that oral aggressive platelet inhibition cause higher cancer risks will turn out to be true, then intensity of platelet inhibition, and especially duration of chronic antiplatelet therapy should be reconsidered. More delicate platelet inhibition, and shorter exposure to oral antiplatelet agents will prevail. [source] BRIEF COMMUNICATION: Rapid and sequential desensitization to both aspirin and clopidogrelINTERNAL MEDICINE JOURNAL, Issue 8 2010S. L. Fernando Abstract Hypersensitivity reactions to aspirin and clopidogrel are 2.5% and 1%, respectively. Dual anti-platelet therapy with these drugs is effective in preventing thrombosis following deployment of stents for cerebrovascular and cardiovascular syndromes. Desensitization therapy with both aspirin and clopidogrel may be required for patients undergoing stent implantation that have experienced hypersensitivity to these agents. We report the case of a 58-year-old woman who developed urticaria and angioedema following aspirin therapy for ischaemic cerebrovascular disease. She developed an identical reaction after clopidogrel was subsequently administered. Investigations revealed the presence of an internal carotid artery aneurysm that required deployment of a stent. Rapid desensitization to aspirin over 5.5 h followed 3 days later by rapid desensitization to clopidogrel over 2.5 h was successfully performed prior to stenting. After 4 months she has tolerated this dual anti-platelet therapy without any adverse reaction. Rapid and sequential desensitization to both aspirin and clopidogrel can be successfully performed for patients who require stent deployment but have hypersensitivity to both these anti-platelet agents. [source] Bleeding risk with AZD6140, a reversible P2Y12 receptor antagonist, vs. clopidogrel in patients undergoing coronary artery bypass grafting in the DISPERSE2 trialINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2009S. Husted Summary AZD6140, the first reversible oral P2Y12 receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped , 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y12 receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects. [source] The challenge of ST-segment elevation myocardial infarctionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2007M. Cohen Summary Background/introduction:, Acute coronary syndromes (ACS) represent a spectrum of ischaemic myocardial events that share a similar pathophysiology. ST-segment elevation myocardial infarction (STEMI), the most severe form of ACS short of sudden cardiac death, is a significant public health problem with an estimated 500,000 STEMI events every year in the United States. Treatment/therapy:, The mortality and morbidity associated with STEMI is significant. Early reperfusion therapy is the most important aspect of the treatment of STEMI. There are two main methods of reperfusion therapy: percutaneous coronary intervention (PCI) and fibrinolytic therapy, with PCI being the preferred method. In addition to standard reperfusion therapy, antithrombotics (unfractionated heparin and low molecular weight heparins) and antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors) are critical adjuncts, effective in the treatment of acute STEMI. Conclusions:, The survival of patients with STEMI depends on rapid diagnosis and optimal early treatment. Guidelines for the management of patients with STEMI recommend PCI within 90 min of presentation and that fibrinolytics are administered within 30 min. However, only a fraction of patients undergo reperfusion within the recommended time. Improvements in protocols for identifying STEMI cases are therefore required to allow reperfusion therapy to be initiated sooner. Secondary prevention is another important aspect of STEMI management, and patients should be encouraged to adopt strategies that reduce the risk of subsequent ischaemic events. [source] Prevention of secondary stroke and transient ischaemic attack with antiplatelet therapy: the role of the primary care physician roleINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2007H. S. Kirshner Summary Background:, Stroke risk is heightened among patients who have had a primary stroke or transient ischaemic attack (TIA). The primary care physician is in the best position to monitor these patients for stroke recurrence. Because stroke recurrence can occur shortly after the primary event, guidelines recommend initiating antiplatelet therapy as soon as possible. Aspirin, with or without extended-release dipyridamole (ER-DP), and clopidogrel are options for such patients. Low-dose aspirin (75,150 mg/day) has the same efficacy as higher doses but with less gastrointestinal bleeding. Clopidogrel remains an option for prevention of secondary events and may benefit patients with symptomatic atherothrombosis, but its combined use with aspirin can harm patients with multiple risk factors and no history of symptomatic cerebrovascular, cardiovascular or peripheral vascular disease. Results:, Low dose aspirin is effective in secondary stroke prevention. Trials assessing aspirin plus ER-DP have shown that the combination is more effective than aspirin monotherapy in preventing stroke, with efficacy increasing among higher risk patients, notably those with prior stroke/TIA. Clopidogrel does not appear to have as much advantage over aspirin in secondary stroke prevention as aspirin plus ER-DP. Smoking cessation and cholesterol, blood glucose and blood pressure control are also important concerns in preventing recurrent stroke. In choosing pharmacological therapy, the physician must consider the individual patient's risk factors and tolerance, as well as other issues, such as use of aspirin among patients with ulcers. Conclusion:, Antiplatelet therapy is effective in secondary stroke prevention. Low dose aspirin can be used first-line, but aspirin plus ER-DP improves efficacy. Clopidogrel is another option in secondary stroke prevention, especially for aspirin-intolerant patients, but it appears to have less advantage over aspirin than aspirin plus ER-DP, and its combined use with aspirin has only marginally better efficacy and increased bleeding risk. [source] Highly Efficient Chemoenzymatic Synthesis of Methyl (R)- o -Chloromandelate, a Key Intermediate for Clopidogrel, via Asymmetric Reduction with Recombinant Escherichia coliADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2008Tadashi Ema Abstract Methyl (R)- o -chloromandelate [(R)- 1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o -chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178,g/L was attained at 20,°C on a 2-g scale (1.0,M). The optimized reaction could be scaled up easily to transform 20,g of 2 in 100,mL of buffer. Three synthetic methods for 2 are compared. [source] The Effect of Transitioning to Medicare Part D Drug Coverage in Seniors Dually Eligible for Medicare and MedicaidJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2008William H. Shrank MD OBJECTIVES: To evaluate medication use, out-of-pocket spending, and medication switching during the transition period for patients dually eligible for Medicaid and Medicare (dual eligibles). DESIGN: Time-trend analysis, using segmented linear regression. SETTING: Patient-level pharmacy dispensing data from January 2005 to December 2006 from a large pharmacy chain with stores in 34 states. PARTICIPANTS: Dual eligibles aged 65 and older. MEASUREMENTS: Changes in utilization, patient copayments, and medication switching were analyzed using interrupted time trend analyses. Utilization and spending were evaluated for five study drugs: clopidogrel, proton pump inhibitors (PPIs), warfarin, and statins (essential drugs covered by Part D plans) and benzodiazepines (not covered through Part D but potentially covered through Medicaid). RESULTS: Drug use for 13,032 dual eligibles was evaluated. There was no significant effect of the transition to Medicare Part D on use of all study drugs, including the uncovered benzodiazepines. Cumulative reductions were seen in copayments for all covered drugs after implementation of Part D, ranging from 25% annually for PPIs to 53% for warfarin, but there was a larger increase in copayments, 91% annually, for benzodiazepines after the transition. The rate of switching medications was 3.0 times as great for the PPIs after implementation of Part D than before implementation, but there was no significant change in the other study drug classes. CONCLUSION: These findings in a single, large pharmacy chain indicate that the transition plan for dual eligibles led to less medication discontinuation and switching than many had expected. The substantially greater cost sharing for benzodiazepines highlights the importance of implementing a thoughtful transition plan when executing such a national policy. [source] |