MedWorm: Clopidogrel

  Journal Scan: Calcium-Channel Blockers Decrease Clopidogrel-Mediated Platelet Inhibition (Heart 2010;96:186-189.)

Adenosine-5-diphosphate (ADP)-inducible platelet reactivity was assessed by light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 162 patients after percutaneous intervention with stent implantation. Results in the fourth quartiles of both assays were considered as high on-treatment. . . (Source: Cardiosource)

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  The Levels of Inflammatory Markers in the Treatment of Stroke study (LIMITS): inflammatory biomarkers as risk predictors after lacunar stroke

Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In ...

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  Bristol Sees Post-Plavix Hit

Bristol-Myers Squibb sees its 2013 earnings about 9% to 13% lower than anticipated 2010 levels due to the expected loss of market exclusivity for its top-selling anti-clotting drug Plavix. (Source: WSJ.com: Health)

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  Stability of generic clopidogrel tablets in monitored dosage systems

Source: North West Medicines Information Centre Area: Evidence > Medicines Q & A Concerns have been raised about the suitability of some generic clopidogrel tablet preparations in monitored dosage systems (MDS). This Medicines Q&A summarises information from SPCs and from manufacturers. (Source: NeLM - Medicines Q & A)

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  Bristol-Myers: 60 drugs in testing, other efforts will help overcome 2012 loss of Plavix sales

TRENTON, N.J. (AP) — Executives at Bristol-Myers Squibb Co. told analysts Thursday at a business briefing that the drugmaker has 60 potential drugs in development, seven in late-stage studies, and plenty of money for dealmaking. "Five potential new... (Source: OrlandoSentinel: Medical Research)

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  Bristol Expects Impact From Plavix Patent Loss

Bristol-Myers Squibb sees its 2013 earnings about 9% to 13% lower than anticipated 2010 levels due to the expected loss of market exclusivity for its top-selling anti-clotting drug Plavix. (Source: WSJ.com: Health)

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  Basic Principles of Platelet Biology and Clinical Implications.

Authors: Angiolillo DJ, Ueno M, Goto S Platelet activation and subsequent accumulation at sites of vascular injury are the first steps in hemostasis. Excessive platelet activation after atherosclerotic plaque rupture or endothelial cell erosion may also lead to the formation of occlusive thrombi, which are responsible for acute ischemic events. Multiple pathways are involved in platelet activation, including those activated by adenosine diphosphate (ADP), thromboxane A(2) (TXA(2)), serotonin, collagen, and thrombin. Antiplatelet agents used for prevention of atherothrombosis have focused on blocking the formation of TXA(2) (eg, aspirin) and interfering with ADP stimulation mediated by the P2Y(12) receptor (eg, clopidogrel). These agents, used alone or in combination, significantly decr...

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  Platelet tissue factor synthesis in type 2 diabetes patients is resistant to inhibition by insulin.

Discussion We characterized the extra- and intracellular mechanisms that couple surface activation to TF-synthesis in adhering platelets. In healthy individuals, TF-synthesis is inhibited by insulin but in patients with type 2 diabetes inhibition is impaired. This leads to the novel finding that platelets from type 2 diabetes patients produce more TF than platelets from matched controls. PMID: 20200314 [PubMed - as supplied by publisher] (Source: Diabetes)

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  [Spontaneous haematoma of the psoas muscle with femoral neuropathy associated with antiplatelet treatment with clopidogrel: Is surgical decompression indicated?]

Authors: Ruiz-Tovar J, Aguilera A, Sánchez-Picot S, Rojo R, García-Villanueva A PMID: 20206343 [PubMed - as supplied by publisher] (Source: Cirugia eEspanola)

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  Fecal Occult Blood Test in Patients on Low-Dose Aspirin, Warfarin, Clopidogrel, or Non-steroidal Anti-inflammatory Drugs

Conclusion  Anticoagulants and antiplatelet medications lower the positive-predictive-value of FOBT for advance colonic neoplasia and should be stopped if clinically feasible prior to stool collection. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10620-010-1150-4Authors Mandeep S. Sawhney, Minneapolis Veterans Affairs Medical Center Division of Gastroenterology Minneapolis MN USAHeather McDougall, Minneapolis Veterans Affairs Medical Center Division of Gastroenterology Minneapolis MN USADouglas B. Nelson, Minneapolis Veterans Affairs Medical Center Division of Gastroenterology Minneapolis MN USAJohn H. Bond, Minneapolis Veterans Affairs Medical Center Division of Gastroenterology Minneapolis MN USA Journal Digestive Diseases and SciencesOnl...

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  Should Omeprazole or Clopidogrel Be Substituted When Given Concomitantly?

An "Ask the Expert" panelist answers readers' questions about the interaction between clopidogrel and PPIs. Medscape Pharmacists (Source: Medscape Today Headlines)

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  Clopidogrel: Mediastinal extracardiac haematoma in an elderly patient: case report

(Source: Reactions)

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  Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial

Conclusion Bivalirudin and unfractionated heparin during PCI provide comparable outcomes at 1 year in biomarker negative patients undergoing PCI after pre-treatment with 600 mg of clopidogrel. Clinical trial registration information: URL www.clinicaltrials.gov; Unique identifier NCT00262054. (Source: European Heart Journal)

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  PLAVIX (Clopidogrel Bisulfate) Tablet, Film Coated [STAT RX USA LLC]

Updated Date: Mar 1, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Patients under anti-platelet therapy

Interruption or maintenance of anti-platelet agents (APAs) during surgical or invasive procedures is associated with an increase in cardiovascular or haemorrhagic complications, respectively. The pharmacology and indications of aspirin, clopidogrel and prasugrel are summarised. The utility and risks of interruption, the optimal delay between stent implantation and surgery, the appropriate window of preoperative interruption, the potential usefulness of bridging, the safest delay between the end of surgery and resumption of APA are detailed in this review. Some non- evidence-based suggestions are given to help the physicians in their daily clinical practice. (Source: Best Practice and Research. Clinical Anaesthesiology)

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  Role of Ticagrelor in Clopidogrel Nonresponders: Resistance Is Futile?

Authors: Tapp L, Shantsila E, Lip GY PMID: 20194888 [PubMed - as supplied by publisher] (Source: Circulation)

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  Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies. The RESPOND Study.

Conclusions-Ticagrelor therapy overcomes nonresponsiveness to clopidogrel, and its antiplatelet effect is the same in responders and nonresponders. Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique Identifier: NCT00642811. PMID: 20194878 [PubMed - as supplied by publisher] (Source: Circulation)

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  PPI for Dual Therapy with Clopidogrel: To Use or not to Use?

Authors: Gross M, Petersen KU PMID: 20195945 [PubMed - as supplied by publisher] (Source: Zeitschrift fur Gastroenterologie)

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  Combination Antiplatelet Therapy for Secondary Stroke Prevention: Enhanced Efficacy or Double Trouble?

Conclusion: Aspirin and clopidogrel combined are associated with more bleeding than aspirin or clopidogrel alone. Summary: Aspirin is effective as an antithrombotic agent for secondary stroke prevention. It reduces the risk of secondary stroke 15% to 20% compared with placebo (BMJ 1994;308:81-106) but fails to prevent many events; therefore, other antithrombotic agents have been investigated for secondary stroke prevention. All antithrombotic agents, however, carry a bleeding risk, and some bleeding episodes are fatal; for example, bleeding associated with antithrombotic agents for secondary prevention leads to higher mortality in patients with acute coronary syndromes (Circulation 2006;114:774-82). In this report the authors sought to compare bleeding risk associated with secondary strok...

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  Clinical relevance of clopidogrel unresponsiveness during elective coronary stenting: Experience with the point-of-care Platelet Function Assay–100 C/ADP

Conclusions: Unresponsiveness to clopidogrel as assessed by the point-of-care test PFA-100C/ADP is an independent major risk factor for thrombotic complications after coronary intervention. (Source: American Heart Journal)

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  Clopidogrel use and clinical events after drug-eluting stent implantation: Findings from the HealthCore Integrated Research Database

Conclusions: Higher clopidogrel use 12 months after drug-eluting stent implantation was associated with a greater risk of subsequent bleeding events. Lower use was associated with a greater risk of death or nonfatal myocardial infarction. (Source: American Heart Journal)

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  Heart failure

New evidence; conclusions changed for: Angiotensin II receptor blockers for diastolic heart failure One RCT added comparing irbesartan versus placebo found no significant difference between irbesartan and placebo in all-cause mortality or in hospital admission for cardiovascular causes at a mean follow-up of 49.5 months. Evidence for effect of irbesartan on hospital admission for cardiovascular disease differs from evidence previously reported for candesartan for this outcome. Effects of angiotensin II receptor blockers as a class in treatment of diastolic heart failure is unclear. Categorisation changed from Likely to be beneficial to Unknown effectiveness. New evidence; conclusion confirmed for: Multidisciplinary intervent...

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  Cilostazol in the Management of Atherosclerosis.

Authors: Sallustio F, Rotondo F, Di Legge S, Stanzione P The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspi...

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  New Details on Potential Adverse Coumarin-Clopidogrel Interaction

The study showing an interaction between coumarin derivatives and the antiplatelet effects of clopidogrel has now been published. Heartwire (Source: Medscape Today Headlines)

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  Un-POPULAR? Utility of Platelet-Function Tests "Modest"

The publication of the first head-to-head trial of platelet-function tests shows that three of the six assays examined helped indicate the likelihood of adverse cardiovascular events among patients taking clopidogrel who were undergoing elective PCI. Heartwire (Source: Medscape Today Headlines)

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  New details on potential adverse coumarin-clopidogrel interaction

The study showing an interaction between coumarin derivatives and the antiplatelet effects of clopidogrel has now been published. For complete story visit theheart.org. (Source: theHeart.org)

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  VASP, VerifyNow P2Y12 assays may best reflect clopidogrel responsiveness

The flow cytometric vasodilator-stimulated phosphoprotein assay and the VerifyNow P2Y12 assay are the most appropriate platelet function tests to monitor peak plasma levels of the active metabolite of clopidogrel, study findings indicate. (Source: MedWire News - Thrombosis)

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  Treatment of Coagulopathy in Intracranial Hemorrhage

Opinion statement  Intracranial hemorrhage (ICH) complicated by coagulopathy is a medical emergency, which can delay neurosurgical intervention, lead to larger hematoma size, and increase mortality until the coagulopathy is corrected. Prompt recognition of coagulopathy during ICH is essential for correct, rapid treatment to reduce ongoing bleeding and improve survival. The proper treatment of a coagulopathic ICH patient is centered on rapid identification of the coagulopathic defect and correction of the underlying coagulopathy to stop acute bleeding. Patients with coagulopathic ICH require admission to a neuro-intensive unit care with management of airway, oxygenation, and systemic arterial and cerebral perfusion pressure; optimization of serum glucose; aggressive treatmen...

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  Genetic Causes of Clopidogrel Nonresponsiveness: Which Ones Really Count?

Pharmacotherapy 30(3): 265-274 Abstract Clopidogrel decreases the morbidity and mortality associated with several cardiovascular diseases. However, clopidogrel is a prodrug that needs to be metabolized to the active thiol metabolite by the cytochrome P450 (CYP) system. This activation is a source of significant interindividual variability in clopidogrel responsiveness. Drug interactions with and genetic variation in CYP3A4, CYP3A5, and CYP2C19 enzymes have been implicated in decreasing active metabolite production. In addition, polymorphisms in the genes encoding P-glycoprotein (an efflux transporter) and purinergic receptor P2Y12 (the active site for clopidogrel) have been studied for their role in clopidogrel responsiveness. Several large studies have recently assessed the role of geneti...

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  Drug Interaction Between Clopidogrel and Proton Pump Inhibitors

Pharmacotherapy 30(3): 275-289 Abstract Proton pump inhibitors (PPIs) have been recommended for reducing the risk of gastrointestinal bleeding associated with dual antiplatelet therapy (aspirin plus clopidogrel). However, studies have found decreased efficacy of clopidogrel when concurrently administered with a PPI. To determine the mechanism of and evidence for the potential interaction between clopidogrel and PPIs, along with the clinical implications of this drug interaction, we reviewed recently published reports of trials that examined the interaction. A MEDLINE database search (1966-September 2009) for English-language reports of clinical trials in human subjects was performed, supplemented by a manual search of reference lists. Four trials that examined surrogate outcomes and eight ...

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  Effect of Combined Aspirin and Extended-Release Dipyridamole Versus Clopidogrel on Functional Outcome and Recurrence in Acute, Mild Ischemic Stroke. PRoFESS Subgroup Analysis.

CONCLUSIONS: Treatment with combined Asp/ER-DP vs clopidogrel in 1360 patients with acute, mild ischemic stroke did not differ in terms of effects on functional outcome, recurrence, death, bleeding, or serious adverse events. Both treatments were practical to administer. PMID: 20181679 [PubMed - as supplied by publisher] (Source: Stroke)

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  Antithrombotic activity of F 16618, a new PAR1 antagonist evaluated in extracorporeal arterio-venous shunt in the rat.

In conclusion, F 16618 exerted a potent antithrombotic activity by intravenous and oral routes, without affecting bleeding time. Furthermore, the antithrombotic activity was potentiated when combined with aspirin or clopidogrel. PMID: 20188709 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)

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  Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation [Original Contribution]

Conclusions  Of the platelet function tests assessed, only light transmittance aggregometry, VerifyNow, and Plateletworks were significantly associated with the primary end point. However, the predictive accuracy of these tests was only modest. None of the tests provided accurate prognostic information to identify low-risk patients at higher risk of bleeding following stent implantation. Trial Registration  clinicaltrials.gov Identifier: NCT00352014 (Source: JAMA)

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  PPIs Likely Risky in Drug-Eluting Stent Recipients

A new report from Washington, DC, adds to the evidence that proton pump inhibitors (PPIs) and clopidogrel don't mix. Reuters Health Information (Source: Medscape Medical News Headlines)

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  Journal Scan: Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation (JAMA 2010;303:754-762.)

The authors prospectively studied 1,069 consecutive patients that underwent elective stent-based PCI at their institution between December 2005 and December 2007. All patients were on clopidogrel, and on-treatment platelet reactivity was measured in all patients using light transmittance aggregomet. . . (Source: Cardiosource)

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  Cleveland Medical Malpractice Attorney Obtains Settlement in Wrongful Death Case

NASA engineer dies after instructions to stop taking Plavix® and Aspirin for elective colonoscopy. Cleveland medical malpractice attorney (http://medical-malpractice.spanglaw.com/) nets settlement for widow. (PRWeb Feb 23, 2010) Read the full story at http://www.prweb.com/releases/top-medical-malpractice/attorneys-cleveland-ohio/prweb3611524.htm (Source: PRWeb: Medical Pharmaceuticals)

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  State of the art of new P2Y12 antagonists

Abstract  The interaction of ADP with its platelet receptor P2Y12 plays a crucial role in platelet activation and thrombogenesis. This article reviews the pharmacology and clinical trials of specific antagonists of P2Y12. Clopidogrel is a thienopyridine with proven antithrombotic efficacy, but it has some important drawbacks: (a) it is a pro-drug that needs to be metabolized to its active metabolite; (b) it has a delayed onset and offset of action and (c) there is high inter-individual variability in pharmacological response. Prasugrel is also a thienopyridine, with faster onset of action and a more uniform inhibition of platelet function compared to clopidogrel, accounting for lower incidence of ischemic events in patients with acute coronary syndromes (ACS) undergoing per...

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  Relation of proton pump inhibitor use after percutaneous coronary intervention with drug-eluting stents to outcomes

Source: Am J Cardiology Area: News According to research published early online in the American Journal of Cardiology, patients who received drug-eluting coronary stents and took clopidogrel had an increased risk of major adverse cardiac events if they were also taking a proton pump inhibitor (PPI).   Researchers sought to examine the effect of a PPI at discharge from the hospital after percutaneous coronary intervention with drug-eluting stents on the incidence of major adverse cardiac events (MACE) at 1 year. The study involved a total of 820 patients of whom 502 patients were not prescribed a PPI at discharge and 318 patients who were prescribed a PPI. All patients were taking clopidogrel, and followed up for 1 year.   The following results were reported:   ....

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  Platelet Function Tests Only Modestly Predict Outcomes

Three tests of platelet function can modestly predict outcomes such as death and stroke in patients taking clopidogrel (Plavix) and undergoing elective coronary stent implantation, but they do not identify patients at higher risk of bleeding, according to a study in the Feb. 24 issue of the Journal of the American Medical Association. (Source: Modern Medicine)

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  Pre-operative clopidogrel use cautioned for cardiac patients

Study findings highlight the risk for bleeding complications in patients who undergo coronary artery bypass graft surgery within a day of clopidogrel treatment. (Source: MedWire News - Thrombosis)

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  Clopidogrel-Proton Pump Inhibitor Interaction: A Primer for Clinicians

(Source: Cardiovascular & Haematological Disorders - Drug Targets(Formerly Current D rug Targets - Cardiovascular & Hematological Disorders))

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  Clinical Trial Summary: Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With AMI (ACCEL-AMI)

The goal of the trial was to evaluate three regimens of antiplatelet therapy after stenting for acute myocardial infarction (AMI): 1) cilostazol plus standard-dose clopidogrel, 2) high-dose clopidogrel, or 3) standard-dose clopidogrel. (Source: Cardiosource)

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  Impact of High-Responsiveness to Dual Antiplatelet Therapy on Bleeding Complications in Patients Receiving Drug-Eluting Stents.

Conclusions: In the present study high-responsiveness to antiplatelet therapy was associated with an increased risk of bleeding with no reduction in adverse cardiac events. Measuring platelet reactivity may be useful for risk stratification according to bleeding complications, as well as adverse cardiac events, in patients treated with drug-eluting stents. PMID: 20173303 [PubMed - as supplied by publisher] (Source: Circulation Journal)

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  European CHMP concludes arbitration on authorisation of Clopidogrel Teva and Clopidogrel Orion

Source: EMEA Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has completed its arbitration procedures initiated because of disagreement among EU Member States regarding the authorisation of Clopidogrel Teva 75 mg Film coated Tablets and Clopidogrel Orion 75 mg Film coated Tablets. The procedures were initiated because of concerns about the use of a clopidogrel base as the active substance, which had to be stabilised using the antioxidant butylated hydroxyanisole. The Committee concluded that the antioxidant in the medicine did not pose a serious risk to patients and that the benefit-risk profile of these medicines was positive and recommended that marketing authorisations should be granted. (Source: NeLM - News)

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  Circulation: Clopidogrel helps halt stroke recurrence after carotid stenting

A large single-center study has found that carotid artery restenosis (post-stenting) greater than 50 percent and cerebral events rather than retinal events are risk factors for recurrent stroke. Clopidogrel, however, reduced the risk, according to the investigation published in the February issue of Circulation: Cardiovascular Interventions. (Source: Cardiovascular Business News)

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  Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Myocardial Infarction: 3-Year Results of the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) Trial

Conclusions: The clinical benefits of SES have been shown to be greater than those of BMS at 3-year follow-up. (Source: Journal of the American College of Cardiology)

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  Slow Response to Clopidogrel Predicts Low Response

Objectives: The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response.Background: Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established.Methods: We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 μmol/l maximal platelet aggregation (MPA) and ΔMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non–ST-segment elevation acute coronary syndrome patients. Low response was defined as ΔMPA (Source: Journal of the America...

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  Initial Clopidogrel Response May Predict Final Response

In patients with acute coronary syndrome, a slow clopidogrel response within the first hour after loading may identify those with a low response after 24 hours and high post-treatment platelet reactivity, according to a study in the Feb. 23 issue of the Journal of the American College of Cardiology. (Source: Modern Medicine)

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  Multivariate-adjusted pharmacoepidemiologic analyses of confidential information pooled from multiple health care utilization databases

Mandated post-marketing drug safety studies require vast databases pooled from multiple administrative data sources which can contain private and proprietary information. We sought to create a method to conduct pooled analyses while keeping information private and allowing for full confounder adjustment.We propose a method based on propensity score (PS) techniques. A set of propensity scores are computed in each data-contributing center and a PS-adjusted analysis is then carried out on a pooled basis. The method is demonstrated in a study of the potentially negative effects of concurrent initiation of clopidogrel and proton pump inhibitors (PPIs) in four cohorts of patients assembled from North American claims data sources. Clinical outcomes were myocardial infarction (MI) hospitalization ...

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  DES in AMI: Benefits Maintained at Three Years in SESAMI

One-year results had suggested sirolimus-eluting stents were superior, driven by a lower rate of repeat procedures; researchers now say that advantage has been maintained out to three years, with no apparent uptick in events when clopidogrel is stopped. Heartwire (Source: Medscape Today Headlines)

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  Review: Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events

Source: Lancet Neurology Area: News The Lancet Neurology has featured a review of the evidence for use of antithrombotic therapies to prevent stroke and other major vascular events among patients with transient ischaemic attack (TIA) and ischaemic stroke.  The following topics and evidence supporting these are discussed:   . Prevention of recurrent ischaemic stroke of arterial origin, using aspirin, clopidogrel, aspirin plus extended-release dipyridamole, other antithrombotic regimens, and promising future antithrombotic regimens . Prevention of recurrent ischaemic stroke of cardiac origin using aspirin, warfarin, aspirin and clopidogrel versus warfarin, aspirin and clopidogrel versus aspirin alone, aspirin and warfarin, direct thrombin inhibitors, factor Xa inhibi...

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  Phenprocoumon attenuates antiplatelet effects of clopidogrel?

Source: Eur Heart J Area: News According to research published early online in the European Heart Journal, phenprocoumon significantly attenuates the antiplatelet effects of clopidogrel. However, the impact of this interaction on the risk of thrombotic and bleeding events after percutaneous coronary intervention (PCI) requires further investigations.   Considering that both clopidogrel and phenprocoumon are metabolised by the hepatic cytochrome P450 system and a drug-drug interaction may exist at this level, and the combination of aspirin, clopidogrel and an oral anticoagulant are often used in certain patients after PCI, researchers sought to investigate the effect of phenprocoumon on the antiplatelet effects of clopidogrel in patients with coronary artery disease.   Th...

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  Warfarin after anterior myocardial infarction in current era of dual antiplatelet therapy: a randomized feasibility trial

Abstract  In the current era of early revascularization and routine use of dual antiplatelet therapy, the incremental benefit of warfarin to reduce the incidence of left ventricular thrombus (LVT) in patients with impaired left ventricular ejection fraction post anterior ST-elevation myocardial infarction (aSTEMI), remains uncertain. The purpose of this study is to assess the feasibility of evaluating the added benefit and safety of triple therapy (TT-warfarin, ASA, and clopidogrel) versus dual therapy (DT-ASA and clopidogrel) in patients at risk of LVT post aSTEMI. Design: Open-label randomized controlled trial. Inclusion: aSTEMI, ejection fraction <40%, and no evidence of LVT. Exclusion: contraindication to, or alternate indication for anticoagulation. Intervention: TT...

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  Poor response to clopidogrel: current and future options for its management

Abstract  Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). Clopidogrel, a thienopyridine antiplatelet agent, has been used to prevent vascular complication in atherothrombotic patients, to prevent stent trombosis in patients undergoing PCI, and in long term prevention of cardiovascular and cerebrovascular events. More than 40 million patients in the world receive clopidogrel but unfortunately about 20% of these are either non or poor responders. Several methods have been used to assess clopidogrel-induced antiplatelet effects. However, none of these tests have been fully standardized or fully agreed upon to measure clopidogrel responsiveness. Nevertheless, many s...

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  Effects of clopidogrel on perioperative blood loss in off pump elective coronary artery bypass surgery. A prospective single blinded observational study

Conclusions  There is no statistically significant difference in blood loss between three groups. In our study we could not find any significant association between perioperative blood loss and clopidogrel. Content Type Journal ArticleDOI 10.1007/s12055-009-0031-yAuthors Ranjith Baskar Karthekeyan, Sri Ramachandra Medical College and Research Institute Department of Cardiothoracic and Vascular Surgery Porur Chennai IndiaHarish Babu, Sri Ramachandra Medical College and Research Institute Department of Cardiothoracic and Vascular Surgery Porur Chennai IndiaMahesh Vakamudi, Sri Ramachandra Medical College and Research Institute Department of Cardiothoracic and Vascular Surgery Porur Chennai IndiaKarthikeyan Selvaraju, Sri Ramachandra Medical College and Research Institute ...

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  Aspirin/clopidogrel/heparin: Haemorrhage: 2 case reports

(Source: Reactions)

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  Clopidogrel: Drug resistance resulting in subacute and very late stent thrombosis, with myocardical infarction: case report

(Source: Reactions)

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  Bivalirudin similar to unfractionated heparin during PCI for patients with angina - one year follow-up

Source: European Heart Journal Area: News This paper presents findings from a one year follow-up of patients enrolled in the ISAR-REACT 3 study, which compared bivalirudin to unfractionated heparin (UFH) in patients with stable and unstable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).   The study included 4,570 biomarker-negative patients undergoing PCI after pre-treatment with 600mg clopidogrel (>2 hours prior to the intervention) and 325-500mg aspirin.  Patients were randomised to double-blind treatment with bivalirudin (0.75mg/kg bolus then infusion of 1.75mg/kg/hr for the duration of the procedure; n=2289) or UFH (140 units/kg bolus followed by placebo infusion for the duration of the procedure; n=2281).  Following the inter...

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  [Review] Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events

Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) and ischaemic stroke of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease activated receptor-1 antagonist, SCH 530348, are currently being evaluated. For patients with TIA and ischaemic stroke of cardiac origin due to atrial fibrillation, vitamin K antagonists (VKAs) are highly effective in preventing recurrent ischaemic stroke but have important limitations and are thus underused. Antiplatelet therapy ...

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  Clopidogrel-induced acute generalized exanthematous pustulosis with elevated Th17 cytokines levels as determined by a drug lymphocyte stimulation test.

Authors: Nakamizo S, Kobayashi S, Usui T, Miyachi Y, Kabashima K PMID: 20163408 [PubMed - as supplied by publisher] (Source: The British Journal of Dermatology)

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  Slippery Platelet Syndromes in Subdural Hematoma

Conclusion  Platelet dysfunction was found in 38% of SDH patients. This finding adds to our understanding of the pathophysiology of SDH. Since platelet transfusions are indicated for platelet dysfunction accompanied by major bleeding or need for surgery, these results impact peri-operative management. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s12028-010-9336-3Authors Paul Taylor Akins, University of California Department of Neurosurgery San Francisco CA USAKern Hayden Guppy, University of California Department of Neurosurgery San Francisco CA USAKamran Sahrakar, University of California Department of Neurosurgery San Francisco CA USAMark Wade Hawk, University of California Department of Neurosurgery San Francisco CA USA Journal Neurocritic...

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  Antiplatelet Therapy Approaches for PCI Evaluated

Patients who receive a loading dose of clopidogrel just before percutaneous coronary intervention have similar ischemic and mortality outcomes to those who receive the antiplatelet therapy well in advance of the procedure (as recommended in professional guidelines), according to research published in the Feb. 1 issue of the American Journal of Cardiology. (Source: Modern Medicine)

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  Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of 'bridging' antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel

Conclusions In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a ‘bridging strategy’ using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding. (Source: British Journal of Anaesthesia)

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  Journal Scan: Comparison of Ticagrelor With Clopidogrel in Patients With a Planned Invasive Strategy for Acute Coronary Syndromes (PLATO): A Randomised Double-Blind Study (Lancet 2010;375:283-293.)

The authors reported the outcome of 13,408 patients who were treated with a planned invasive strategy for an ACS and were enrolled in the PLATO trial. In this trial, patients were randomly assigned in a double dummy fashion to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day. . . (Source: Cardiosource)

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  Takeda Announces Initiation Of Trial To Study The Concomitant Use Of Dexlansoprazole And Other Proton Pump Inhibitors With Plavix(R)

Takeda Global Research & Development Center, Inc., U.S., (TGRD U.S.) announced that it has initiated a trial to study how dexlansoprazole and several other proton pump inhibitors (PPIs) affect the pharmacokinetics and pharmacodynamics of Plavix (clopidogrel bisulfate) in healthy subjects. Takeda has been evaluating all published data and communications from the U.S. Food and Drug Administration (FDA) regarding the potential risks associated with concomitant use of clopidogrel and PPIs... (Source: Health News from Medical News Today)

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  Takeda Announces Initiation of Trial to Study the Concomitant Use of Dexlansoprazole and Other Proton Pump Inhibitors With Plavix(R) (Clopidogrel Bisulfate)

DEERFIELD, IL - (HSMN NewsFeed) - Takeda Global Research & Development Center, Inc., U.S., (TGRD U.S.) announced today that it has initiated a trial to study how dexlansoprazole and several other proton pump inhibitors (PPIs) affect the pharmacokinetics an... BiopharmaceuticalsTakeda Pharmaceutical, dexlansoprazole, Plavix, clopidogrel (Source: HSMN NewsFeed)

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  Bristol-Myers Squibb to Stop All Non-Mandated Salary Raises in 2010 to Cut Costs

From Canadian Press DataFile (February 5, 2010) NEW YORK -- Drugmaker Bristol-Myers Squibb Co. says it is freezing employee salaries for 2010 as it cuts spending and prepares for a drop in sales of its blockbuster blood thinner Plavix. The New... (Source: Drugs.com - Pharma News)

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  Bristol-Myers Squibb to Stop All Non-Mandated Salary Raises in 2010 to Cut Costs

From Canadian Press DataFile (February 5, 2010) NEW YORK -- Drugmaker Bristol-Myers Squibb Co. says it is freezing employee salaries for 2010 as it cuts spending and prepares for a drop in sales of its blockbuster blood thinner Plavix. The New... (Source: Drugs.com - Pharma News)

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  The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy

Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.The study cohort consisted of 662 patients with adenocarcinoma of the prostate who received radiotherapy (RT) with curative intent. Among those 622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin). All patients received external-beam RT, permanent seed implantation, or a combination of both. Prostate-specific antigen (PSA) values were monitored for biochemical control of disease.At a median follow-up of 49 months, the biochemical control rate at 4-years was sig...

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  Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

In conclusion, in patients undergoing percutaneous coronary intervention with drug-eluting stents and receiving clopidogrel, the prescription of a PPI at discharge was associated with a greater rate of MACE at 1 year. (Source: The American Journal of Cardiology)

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  Absolute platelet aggregation unaffected by tapered clopidogrel cessation

Study findings indicate that tapering the end of clopidogrel therapy does not result in significantly lower absolute platelet aggregation values compared with abrupt termination in patients with drug-eluting stents. (Source: MedWire News - Thrombosis)

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  Triple Therapy: Triple Safety or Triple Danger?

We read the report by Zinn and Feit with great interest. We learned from the article by Zinn and Feit to individualize care and tailor therapy according to the risk for bleeding but also to ischemic and embolic complications. Zinn and Feit state that all data were retrospective and that most came from single-center series. A randomized trial with head-to-head assessment of differing antithrombotic regimens is needed. Zinn and Feit state that there are no randomized trials prospectively addressing a comparison of triple therapy and dual-antiplatelet therapy to guide clinical decision making. In patients with indication for long-term oral anticoagulation (OAC) who need to undergo percutaneous coronary intervention, there are theoretically 4 possibilities: the combinations of aspirin plus clo...

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  Warning on treating MI with long-term clopidogrel

GPs treating patients at risk of recurrent myocardial infarction with clopidogrel may be keeping some of them on the drug for far longer than necessary, researchers believe. (Source: Pulse)

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  Review: Proton pump inhibitor and clopidogrel interaction

Source: Am J Gastroenterol Area: News This review on the interaction between proton pump inhibitors (PPIs) and clopidogrel addresses the following questions and topics:   . What is the role of clopidogrel in cardiovascular disease? . What is the risk of GI bleeding with clopidogrel? . Do PPIs decrease GI bleeding in patients taking clopidogrel? . Clopidogrel metabolism . PPI metabolism . Do PPIs influence clopidogrel's pharmacodynamic effects? . Do PPIs influence clopidogrel's clinical efficacy? . Recommendations to health-care providers   The authors conclude "the current evidence does not justify the conclusion that PPIs decrease the clinical efficacy of clopidogrel. Nonetheless, until further reliable data become a...

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  Clopidogrel and calcium-channel blockers: a clinically important interaction?

(Source: Heart)

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  Calcium-channel blockers decrease clopidogrel-mediated platelet inhibition

Conclusion CCBs decrease clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease. (Source: Heart)

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  A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment

Conclusions: Tapering of clopidogrel does not result in lower PA values after clopidogrel withdrawal. The course of PA values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets. (Source: Journal of the American College of Cardiology)

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  Review: Combination antithrombotic therapies

Source: Circulation Area: News This review summarises the role of combination antiplatelet therapies in the treatment and prevention of atherothrombosis. The following topics and drug combinations are discussed:   . Pathophysiology of atherothrombosis . Aspirin . Aspirin dose and bleeding . Thienopyridines . Aspirin monotherapy vs. thienopyridine monotherapy . Thienopyridine plus aspirin: stenting . Clopidogrel plus aspirin and vs. aspirin monotherapy for acute coronary syndromes, primary and secondary prevention . clopidogrel plus aspirin vs. clopidogrel monotherapy: TIA and stroke . Limitations of clopidogrel plus aspirin . Overcoming clopidogrel non-esponsiveness o Higher doses o Prasugrel plus asp...

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  No Rebound Seen in Platelet Aggregation After Clopidogrel

There was no rebound in platelet aggregation observed in cardiovascular patients who stopped taking clopidogrel abruptly or tapered off the medication gradually after the prescribed course of treatment, according to a study in the Feb. 9 issue of the Journal of the American College of Cardiology. (Source: Modern Medicine)

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  CYP2C19-17 linked to elevated clopidogrel bleeding risk

Patients carrying the cytochrome P450 2C19-17 variant have an enhanced response to clopidogrel treatment, increasing their risk for bleeding, caution German researchers. (Source: MedWire News - Thrombosis)

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  No Rebound Effect With Platelets After Stopping Clopidogrel

Tapering off clopidogrel treatment after the implantation of a drug-eluting stent does not result in lower platelet-aggregation values than those seen after the antiplatelet medication is abruptly stopped. Heartwire (Source: Medscape Today Headlines)

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  High Maintenance Dosage of Clopidogrel is Associated with a Reduced Risk of Stent Thrombosis in Clopidogrel-Resistant Patients

(Source: American Journal of Cardiovascular Drugs)

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  Omeprazole and clopidogrel: Should clinicians be worried?

The US Food and Drug Administration has issued a warning that omeprazole (Prilosec) reduces the antiplatelet activity of clopidogrel (Plavix) by about 50%. However, the warning is based largely on ex vivo data. Preliminary results from a randomized clinical trial revealed no effect on cardiovascular outcomes when omeprazole was given with clopidogrel. We recommend that physicians continue to prescribe a proton pump inhibitor for patients receiving dual antiplatelet therapy who are at risk of gastrointestinal bleeding or have an indication for use of a proton pump inhibitor. (Source: Cleveland Clinic Journal of Medicine)

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  Impact of genetic variation on cardiovascular outcomes in clopidogrel-treated patients with PCI

Source: Circulation Area: News Recent research has suggested that the CYP2C19*17 allelic variant is associated with increased transcriptional activity, leading to extensive metabolisation of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment. To investigate this further, this study assessed the impact of CYP2C19*17 on ADP-induced platelet aggregation, the risk of bleeding, and stent thrombosis in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI).   Study investigators enrolled 1524 patients undergoing PCI after pre-treatment with a loading dose of 600 mg clopidogrel. The primary safety end point was the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria, a...

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  Efficacy and Safety of Ticagrelor: A Reversible P2Y12 Receptor Antagonist (March) (CE).

CONCLUSIONS: Ticagrelor's improved pharmacokinetic and pharmacodynamic profile builds upon the limitations of currently available P2Y12 receptor antagonists. Ticagrelor represents a promising approach for the prevention of cardiovascular events in patients with ACS. PMID: 20124464 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

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  In vitro effects of recombinant activated factor VIIa (NovoSeven) on clopidogrel-induced platelet inhibition.

Authors: Szlam F, Tanaka KA, Rumph B, Bolliger D, Levy JH PMID: 20135070 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)

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  Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis.

Authors: Sofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF We performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients follo...

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  Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome.

Authors: Cuisset T, Hamilos M, Delrue L, Frère C, Verhamme K, Bartunek J, Saut N, Bonnet JL, Eijgelsheim M, Wijns W, Alessi MC, Barbato E Platelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet alpha2A- (alpha2A-AR) and beta2-adrenergic receptor (beta2-AR) stimulation. It was the objective of this study to assess the potential influence of alpha2A-AR and beta2-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3...

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  No rebound effect with platelets after stopping clopidogrel

Tapering off clopidogrel treatment after the implantation of a drug-eluting stent does not result in lower platelet-aggregation values than those seen after the antiplatelet medication is abruptly... For complete story visit theheart.org. (Source: theHeart.org)

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  European Medicines Agency (EMA)

Public Statement on the withdrawal of the marketing authorisation in the European Union for Clopidogrel BMS (clopidogrel) (Source: National Prescribing Centre eCAB Week in Review)

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  No Rebound Seen After Antiplatelet Withdrawal (CME/CE)

No evidence of a platelet aggregation rebound occurs with abrupt discontinuation of clopidogrel (Plavix) in patients undergoing percutaneous coronary intervention (PCI), investigators in a randomized clinical trial concluded. (Source: MedPage Today Cardiovascular)

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  Triple antiplatelet therapy reduces ischemic events after drug-eluting stent implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces Adverse Serious cardiac Events (DECREASE registry)

Conclusions: Triple antiplatelet therapy significantly reduced 12-month risks of stent thrombosis and MI after DES implantation compared with dual antiplatelet therapy without increased risk of bleeding complications. The longer duration of triple therapy after DES implantation was associated with the lower risk of stent thrombosis and MI. (Source: American Heart Journal)

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  Lack of outcome benefit and clopidogrel "resistance".

This study was the first in a decade to challenge clopidogrel monopoly, and to indirectly test the "resistance" hypothesis. The primary endpoint was the rate of cardiovascular death, non-fatal myocardial infarction, or stroke, and occurred in 12.1% of patients treated with clopidogrel, and 9.9% of patients randomised to prasugrel, suggesting impressive vascular outcome benefit of prasugrel over clopidogrel. However, the Food and Drug Administration (FDA) presented more balanced, and realistic outlook on TRITON. While very early periprocedural benefit exists, long-term prasugrel therapy yielded identical to clopidogrel vascular outcomes among 13,608 TRITON patients challenging the postulate that clopidogrel "resistance" phenomenon is clinically relevant. Despite the fact that prasugrel 10 m...

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  The influence of variation in the P2Y12 receptor gene on in vitro platelet inhibition with the direct P2Y12 antagonist cangrelor.

Authors: Bouman HJ, van Werkum JW, Rudez G, Leebeek FW, Kruit A, Hackeng CM, Ten Berg JM, de Maat MP, Ruven HJ Novel P2Y12 inhibitors are in development to overcome the occurrence of atherothrombotic events associated with poor responsiveness to the widely used P2Y12 inhibitor clopidogrel. Cangrelor is an intravenously administered P2Y12 inhibitor that does not need metabolic conversion to an active metabolite for its antiplatelet action, and as a consequence exhibits a more potent and consistent antiplatelet profile as compared to clopidogrel. It was the objective of this study to determine the contribution of variation in the P2Y12 receptor gene to platelet aggregation after in vitro partial P2Y12 receptor blockade with the direct antagonist cangrelor. Optical aggregometry was perfor...

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  Ticagrelor With Invasive Strategy Cut Deaths

Major Finding: ACS patients with a planned invasive strategy who received ticagrelor had a 16% reduction in risk of cardiovascular death, MI, or stroke, compared with patients given clopidogrel over 1 year. (Source: Cardiology News)

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  Antiplatelet therapy with clopidogrel or ticlopidine reduces intimal hyperplasia in an animal model of experimental arterial injury.

Authors: Kloppenburg G PMID: 20149999 [PubMed - in process] (Source: Anadolu Kardiyol Der...)

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  Inhibitory effects of ticlopidine and clopidogrel on the intimal hyperplastic response after arterial injury.

CONCLUSION: The results of our study suggest that ticlopidine and clopidogrel, which are widely used in antiplatelet treatment in clinics, can similarly prevent the development of intimal hyperplasia after experimental arterial injury. PMID: 20149998 [PubMed - as supplied by publisher] (Source: Anadolu Kardiyol Der...)

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  [Epidemiological study of the cardiovascular risk factors and clinical medications in patients with cardiovascular diseases in Guangzhou hospitals.]

CONCLUSION: The cardiovascular risk factors and clinical medications underwent significant changes in Guangzhou hospitals in the period from 1995 to 2005, and the blood pressure, blood glucose, hypertriglyceridemia of the patients did not appear to be well controlled. The application rate of ACEI, ARB, beta-blockers, diuretics, aspirin, clopidogrel and statins increased rapidly for treatment of cardiovascular diseases, and these drugs have become the first-line drugs. PMID: 20159710 [PubMed - in process] (Source: Journal of Southern Medical University)

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  Clopidogrel and proton pump inhibitors: Are the goal posts shifting?

Modern treatment of acute coronary syndrome involves reducing platelet activity. Currently this is achieved orally by generally targeting 2 pathways of platelet activation, the cyclooxygenase pathway, with aspirin and the ADP receptor, most commonly with clopidogrel. This leads to a reduction in death from cardiovascular causes, non fatal myocardial infarction and stroke in both patients treated with medical therapy and in those undergoing percutaneous coronary angioplasty . Any impact of reducing the efficacy of such antiplatelet therapies may lead to potentially worse outcomes in coronary patients. Therefore any drug-drug interaction that impairs antiplatelet drug efficacy should be avoided. (Source: Thrombosis Research)

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  Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy

Abstract: Introduction: Currently, there is an intense debate about whether comedication with proton pump inhibitors (PPIs) weakens the antiplatelet effect of clopidogrel in patients undergoing coronary stent implantation. Competing mechanisms on the hepatic cytochrome 2C19 level are proposed. The aim of this study was to assess the impact of PPI treatment on clopidogrel response by measuring the ex vivo platelet aggregation in patients with coronary intervention.Methods: 1425 consecutive patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention were enrolled in this single centre study. PPI comedication was defined as PPI intake ≥1 week prior to a 600 mg clopidogrel loading dose. PPI treatment was based on physician preference. Residual platelet a...

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  Clopidogrel increases blood transfusion and hemorrhagic complications in patients undergoing cardiac surgery.

CONCLUSIONS: Patients receiving clopidogrel within 24 hours of surgery are at increased risk for transfusion and hemorrhagic complication. Timing of surgery for patients receiving clopidogrel should take into account the interval from the last dose. PMID: 20103308 [PubMed - indexed for MEDLINE] (Source: The Annals of Thoracic Surgery)

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  High-Intensity Exercise for Patients in Cardiac Rehabilitation After Myocardial Infarction

Mrs. R is a 62-year-old woman with a history of diabetes, hypertension, hyperlipidemia, smoking, and obesity who was admitted 6 weeks ago with acute onset of substernal chest pain while climbing stairs. She had an acute myocardial infarction (MI) with ST-segment elevation on her cardiogram and was emergently taken for cardiac catheterization. Drug-eluting stents were placed in the first diagonal and second obtuse marginal arteries. She is now taking clopidogrel bisulfate, beta blockade, and aspirin and has been counseled regarding lifestyle modifications. Her insurance has approved her for only 18 sessions of outpatient cardiac rehabilitation (CR), and she is planning to make her annual migration south for the winter in 8 weeks. (Source: PM&R)

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  ATP induced microglial cell migration through non-transcriptional activation of matrix metalloproteinase-9.

In this study, we investigated whether ATP modulates microglial migration by regulating the activity of matrix metalloproteinases (MMPs). ATP induced rapid microglial migration and increased the activity of MMP-9 in the culture supernatants (secreted compartments) in a concentration-dependent manner. The increased activity of secreted MMP-9 is due to the increased protein secretion, but not by the increased MMP-9 mRNA and protein expression. Inhibition of MMP-9 activity by treatment with specific inhibitors including GM6001 and SB-3CT prevented ATP-induced microglial migration. ATP-induced microglial migration was also inhibited by P2Y receptor antagonists including clopidogrel as well as PI3K inhibitor such as wortmanin. Taken together, ATP non-transcriptionally increased MMP-9 activity b...

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  Acute myocardial infarction in a patient with post-splenectomy thrombocytosis: a case report and review of literature.

We describe a case of acute myocardial infarction in a young heavy smoker with RT following splenectomy. Coronary angiography showed a linear filling defect at mid-part of left anterior descending artery. We performed balloon angioplasty and stenting for this lesion. Aspirin and clopidogrel were administered. His in-hospital course was uneventful and platelet count returned to the normal range at four month follow-up. We concluded that RT may not be an entirely benign process, especially in patients with a history of smoking. Regular monitoring of platelet count, and possibly antithrombotic agents like aspirin prescription for high risk patients with moderate thrombocytosis, may be useful. PMID: 20104461 [PubMed - in process] (Source: Cardiology Journal)

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  Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study

Conclusions: We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain. (Source: BMC Cardiovascular Disorders)

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  [Correspondence] HORIZONS-AMI

The 12-month results of HORIZONS-AMI (Oct 3, p 1149) show that, in patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), anticoagulation with bivalirudin reduced net adverse clinical events and major bleeding at 1 year compared with heparin plus a glycoprotein IIb/IIIa inhibitor. The difference, evident almost immediately after the procedure, was due to reduced bleeding with bivalirudin. Very early, but not 12-month, stent thrombosis was increased in the bivalirudin group. Of interest, major adverse cardiac events were lower in those given a 600 mg clopidogrel loading dose than in those given 300 mg, irrespective of antithrombin treatment. (Source: LANCET)

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  Influence of Microenvironment pH, Humidity, and Temperature on the Stability of Polymorphic and Amorphous Forms of Clopidogrel Bisulfate.

Authors: Raijada DK, Singh S, Bansal AK The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline pH, respectively. The samples without and with stressors were subjected for 3 months to (1) 0% RH, 25% RH, 75% RH, and 85% RH at 40 degrees C and also to (2) 60 degrees C, 80 degrees C, and 100 degrees C at 0% RH. In case of solid samples without stressors, the mixture of polymorphic and amorphous forms showed more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case ...

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  Safety of carotid endarterectomy while on clopidogrel (Plavix).

Conclusions Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA. PMID: 20113164 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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  Balancing the benefits and risks of antiplatelet agents in patients with non-ST-segment elevated acute coronary syndromes and undergoing percutaneous coronary intervention

Abstract  Selecting appropriate antiplatelet therapy requires close attention to the delicate balance between reducing risk of ischemic events while minimizing bleeding risk. The broad range of available agents, while permitting tailoring of pharmacotherapy to individual patients, also complicates selection of optimal regimens. Platelet physiology provides an underpinning for the rationale behind pharmacotherapeutic strategies for patients with non-ST-segment elevated acute coronary syndromes (NSTE ACS) undergoing percutaneous coronary intervention (PCI). The same mechanisms of action that confer anti-ischemic benefit with antiplatelet agents may also be associated with increased risk. In the context of ACS and PCI, antiplatelet agents are used in complex strategies and com...

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  Clopidogrel Increases Blood Transfusion and Hemorrhagic Complications in Patients Undergoing Cardiac Surgery [ORIGINAL ARTICLES: ADULT CARDIAC]

Conclusions Patients receiving clopidogrel within 24 hours of surgery are at increased risk for transfusion and hemorrhagic complication. Timing of surgery for patients receiving clopidogrel should take into account the interval from the last dose. (Source: The Annals of Thoracic Surgery)

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  Timing of PCI clopidogrel does not affect bleeding outcomes

Treatment with a high dose of clopidogrel immediately before or after percutaneous coronary intervention results in short-term ischemic outcomes and long-term mortality similar to those of patients who receive clopidogrel according to the current guidelines, research shows. (Source: MedWire News - Thrombosis)

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  Aspirin/clopidogrel: Subdural haematoma: case report

(Source: Reactions)

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  Clopidogrel/ticlopidine: Hypersensitivity followed by successful clopidogrel desensitisation: case report

(Source: Reactions)

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  Clopidogrel Interaction [Health Agencies Update]

(Source: JAMA)

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  Endothelial dysfunction linked to clopidogrel resistance pre-PCI

Impaired endothelial function in angina patients awaiting percutaneous coronary intervention appears to be associated with heightened platelet reactivity after loading clopidogrel, study findings show. (Source: MedWire News - Cardiology)

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  New Variant Linked to Platelet Response and Bleeding Events With Clopidogrel

Those homozygous for the CYP2C19*17 polymorphism had significantly reduced platelet aggregation and significantly greater risks of bleeding than individuals without the variant, although there was no difference in rates of stent thrombosis, report investigators. Heartwire (Source: Medscape Today Headlines)

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  New variant linked to platelet response and bleeding events with clopidogrel

Those homozygous for the CYP2C19*17 polymorphism had significantly reduced platelet aggregation and significantly greater risks of bleeding than individuals without the variant, although there was no... For complete story visit theheart.org. (Source: theHeart.org)

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  Antiplatelet Therapy and Outcomes after Trauma: Identifying a New High-Risk Group

Conclusion: Despite being less severely injured and requiring fewer blood transfusions, there is a markedly increased mortality rate in trauma patients on clopidogrel who suffered a fall compared to patients not injured by a fall. These findings identify a new high risk group in the trauma population that requires further study. (Source: Journal of Surgical Research)

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  Pelvic Fractures and Antiplatelet Agent Use: Why Should We Care? S

Conclusions: The use of APA at the time of injury does not significantly affect overall complications or mortality in patients with PFx. Despite greater early actual and corrected hemoglobin drops and increased number of early (within the initial 24hours) blood transfusions in the APA group, no differences were seen in platelet or late blood transfusions when comparing the two groups. (Source: Journal of Surgical Research)

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  Two Clopidogrel Loading Doses Compared in Patients With STEMI

What's the best loading dose of clopidogrel before primary percutaneous coronary intervention in patients with ST-segment elevation MI? Journal Watch (Source: Medscape Today Headlines)

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  Antiplatelet effect of 50-mg maintenance dose of clopidogrel compared to 200 mg ticlopidine: a preliminary study

Abstract  In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 μmol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% ± 11% vs 38% ± 15%, not significan...

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  [Comment] Ticagrelor in ACS: redefining a new standard of care?

Tremendous progress has been achieved over the past decade in the treatment of acute coronary syndromes (ST-segment elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], and unstable angina). In STEMI, primary percutaneous coronary intervention compared with fibrinolytic therapy reduces mortality, reinfarction, stroke, infarct size, and recurrent ischaemia. In moderate-risk and high-risk patients with NSTEMI, early angiography followed by revascularisation with either percutaneous coronary intervention or coronary artery bypass graft surgery compared with a more conservative approach reduces the rates of death or myocardial infarction, recurrent ischaemia, and rehospitalisation. Drug-eluting stents have been shown to be safe in acute coronary syndromes, and, compared with bare-metal...

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  [Articles] Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study

Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. (Source: LANCET)

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  Calcium-channel blockers blunt clopidogrel action after stenting

Calcium-channel blocker therapy appears to interfere with clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease, study results show. (Source: MedWire News - Cardiology)

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  Triple, Dual Restenosis Prevention Therapies Studied

Antiplatelet therapy including aspirin, clopidogrel and cilostazol helps prevent late stenosis following stent placement better than standard therapy with only aspirin and clopidogrel, according to a study in the Jan. 15 issue of the American Journal of Cardiology. (Source: Modern Medicine)

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  Pre-PCI clopidogrel response testing may reduce major bleeding risk

Testing platelet response to clopidogrel before percutaneous coronary intervention could help identify patients at risk for major bleeding, German researchers suggest. (Source: MedWire News - Thrombosis)

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  Clopidogrel Loading Can Sometimes Be Delayed Until PCI

In patients undergoing percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction, delaying clopidogrel loading until just before or after PCI does not appear to worsen outcomes compared with the standard approach of giving the drug before angiography, new research shows. Reuters Health Information (Source: Medscape Cardiology Headlines)

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  Clopidogrel/PPI interaction insignificant

(Source: Reactions)

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  Clopidogrel: Urticaria: case report

(Source: Reactions)

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  International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding.

Authors: Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, Sinclair P, DESCRIPTION: A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RECOMMENDATIONS: Recommendations emphasize early risk stratification, b...

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  High Residual Platelet Reactivity After Clopidogrel: Extent of Coronary Atherosclerosis and Periprocedural Myocardial Infarction in Patients With Stable Angina Undergoing Percutaneous Coronary Intervention

Conclusions Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI. (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)

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  Therapeutic Effect of Clopidogrel on Cutaneous Polyarteritis Nodosa [Correspondence]

(Source: Archives of Dermatology)

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  [Reflection and Reaction] EARLY antiplatelet treatment after ischaemic stroke

Management of patients with recent ischaemic stroke includes measures to prevent recurrent thromboembolic events. The risk of early recurrent stroke, particularly within the first few days, can be high among people whose ischaemic stroke resolves spontaneously and rapidly (ie, in patients with transient ischaemic attack [TIA]). For this reason, management of these patients is approached with a sense of urgency and with the aim of initiating therapies rapidly to prevent a subsequent severe, disabling stroke. Antiplatelet drugs, such as aspirin monotherapy, clopidogrel alone or with aspirin, or the combination of aspirin and dipyridamole (most commonly in an extended-release formulation), are commonly prescribed. In two large trials, some success has been reported in improving outcomes among...

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  Clinical Trial Summary: PLATelet inhibition and patient Outcomes (PLATO)

The goal of the trial was to evaluate the safety and efficacy of treatment with ticagrelor, a novel reversible oral P2Y12 receptor antagonist, compared with clopidogrel among patients with an acute coronary syndrome (ACS) with or without ST-segment elevation. (Source: Cardiosource)

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  Genotyping, Clopidogrel Metabolism, and the Search for the Therapeutic Window of Thienopyridines.

Authors: Steinhubl SR PMID: 20083686 [PubMed - as supplied by publisher] (Source: Circulation)

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  Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement.

Conclusions-CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding. PMID: 20083681 [PubMed - as supplied by publisher] (Source: Circulation)

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  The Combination of Clopidogrel Plus Aspirin to Treat Atrial Fibrillation

Content Type Journal ArticleCategory Clinical Trial ReportDOI 10.1007/s11886-009-0078-9Authors Jesse Weinberger, One Gustave L. Levy Place Mount Sinai School of Medicine, Department of Neurology Box, 1052 New York NY 10029 USA Journal Current Cardiology ReportsOnline ISSN 1534-3170Print ISSN 1523-3782 (Source: Current Cardiology Reports)

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  Ticagrelor benefits seen in ACS patients undergoing invasive treatment

The reversible P2Y12 inhibitor ticagrelor reduces the risk for death and cardiovascular events compared with clopidogrel therapy in patients with acute coronary syndromes, show the results of PLATO-Invasive. (Source: MedWire News - Thrombosis)

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  Plavix-Prilosec interaction warning

FDA has announced that concomitant use of omeprazole (Prilosec, AstraZeneca, and Prilosec OTC, Procter & Gamble) and clopidogrel (Plavix, Sanofi Aventis/Bristol-Myers Squibb) can reduce the anti-clotting effectiveness of clopidogrel. (Source: Drug Topics - Top News)

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  Plavix-Prilosec interaction warning

FDA has announced that concomitant use of omeprazole (Prilosec, AstraZeneca, and Prilosec OTC, Procter & Gamble) and clopidogrel (Plavix, Sanofi Aventis/Bristol-Myers Squibb) can reduce the anti-clotting effectiveness of clopidogrel. (Source: Drug Topics - Clinical News)

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  Plavix-Prilosec interaction warning

FDA has announced that concomitant use of omeprazole (Prilosec, AstraZeneca, and Prilosec OTC, Procter & Gamble) and clopidogrel (Plavix, Sanofi Aventis/Bristol-Myers Squibb) can reduce the anti-clotting effectiveness of clopidogrel. (Source: Drug Topics - Pharmacy News)

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  Plavix-Prilosec interaction warning

FDA has announced that concomitant use of omeprazole (Prilosec, AstraZeneca, and Prilosec OTC, Procter & Gamble) and clopidogrel (Plavix, Sanofi Aventis/Bristol-Myers Squibb) can reduce the anti-clotting effectiveness of clopidogrel. (Source: Modern Medicine)

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  A Scalable Synthesis of (±)-2-Oxoclopidogrel

SynlettDOI: 10.1055/s-0029-1219177AbstractAs a precondition for detailed pharmacological investigations, an efficient chemical method for the conversion of the antiplatelet drug clopidogrel into its first metabolite 2-oxoclopidogrel was developed. The one-pot procedure, which can easily be performed on a gram scale, exploits the selective borylation of a di-­anionic intermediate derived from clopidogrel with subsequent oxidative workup.[...]© Georg Thieme Verlag Stuttgart ˙ New YorkGet connected:Table of contents  |  Abstract  |  Full text (Source: Synlett)

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  Evaluation of Platelet Inhibition by Tirofiban in Patients Stratified According to Aspirin and Clopidogrel Responsiveness: The 3T/2R (Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel)

Large interindividual variability in the response to aspirin and clopidogrel (oral antiplatelet agents [OAA]) is known to exist, and previous studies showed that poor response to OAA is associated with higher risk of ischemic complications after percutaneous coronary intervention (PCI) (). Whether poor responders to OAA display similar inadequate platelet inhibition (PI) also after glycoprotein (GP) IIb/IIIa inhibitor administration remains undefined. (Source: Journal of the American College of Cardiology)

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  Novel Antiplatelet Called New Standard in ACS (CME/CE)

Among patients who underwent planned stenting for treatment of acute coronary syndromes, those treated with the investigational antiplatelet agent ticagrelor (Brilinta) had fewer cardiovascular events than patients who received clopidogrel (Plavix). (Source: MedPage Today Cardiovascular)

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  Ticagrelor Better Than Clopidogrel in Early Invasive Treatment of ACS

(Source: Physician's First Watch current issue)

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  Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications

Conclusion Chronic oral combination antiplatelet regimens are associated with a very high (56.5–60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging. (Source: European Heart Journal)

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  Anticlotting Medication Tricagrelor Reduces Death Rates For Heart Attack Patients (PLATO Trial)

An article Online First and in an upcoming edition of The Lancet reports the new analysis of the PLATO trial (PLATelet inhibition and patient Outcomes). New research shows that the stronger anticlotting medication tricagrelor reduces death rates without increasing bleeding compared with the current standard treatment of clopidogrel for heart attack patients. The article is the work of Dr Christopher P Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA, and colleagues... (Source: Health News from Medical News Today)

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  Anticlotting Medication Tricagrelor Reduces Death Rates For Heart Attack Patients (PLATO Trial)

An article Online First and in an upcoming edition of The Lancet reports the new analysis of the PLATO trial (PLATelet inhibition and patient Outcomes). New research shows that the stronger anticlotting medication tricagrelor reduces death rates without increasing bleeding compared with the current standard treatment of clopidogrel for heart attack patients... (Source: Stroke / Neuroprotection News From Medical News Today)

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  New Anticlotting Drug Beats Plavix

Title: New Anticlotting Drug Beats PlavixCategory: Health NewsCreated: 1/14/2010 9:49:00 AMLast Editorial Review: 1/14/2010 9:49:58 AM (Source: MedicineNet Cholesterol General)

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