Clopidogrel resistance: identifying and overcoming a barrier to effective antiplatelet treatment.

Abstract:

:Clopidogrel is an inhibitor of the ADP receptor P2Y12 and platelet aggregation. It is widely used for the management of atherothrombotic disease in patients who have experienced severe vascular events such as stroke or myocardial infarction or with peripheral artery disease. However, some patients show "resistance" to clopidogrel, and show impaired inhibition of platelet aggregation. In this review, I discuss the clinical evidence of the extent of the problem, potential implications for future cardiovascular events and clinical tests to assess platelet aggregation. I also discuss the mechanisms that appear responsible for clopidogrel resistance. Clopidogrel is administered as a prodrug and the active metabolite is generated by the cytochrome P450 system. Therefore, inadequate responses to clopidogrel may be caused by polymorphisms in one or more of the cytochrome P450 enzymes and interaction/competition with other drugs metabolized by the cytochrome P450 system (e.g., statins and proton pump inhibitors). Finally, I discuss the therapeutic options available for patients with known or suspected clopidogrel resistance, including the use of drugs with alternative molecular targets (e.g., cilostazol), metabolized via different pathways (e.g., prasugrel) or administered in an active form (e.g., ticagrelor). Clopidogrel resistance is a clinically significant problem with potentially severe consequences if it is not identified or managed appropriately. The availability of point-of-care assays and novel treatments provide clinicians with an extensive array of tools that should aid in the management of atherothrombotic diseases/events, and reduce the risk of future severe events in these patients.

journal_name

Cardiovasc Ther

authors

Uchiyama S

doi

10.1111/j.1755-5922.2010.00202.x

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

e100-11

issue

6

eissn

1755-5914

issn

1755-5922

journal_volume

29

pub_type

杂志文章,评审
  • Regenerative therapy in peripheral artery disease.

    abstract::Patients with peripheral artery disease (PAD) and critical limb ischemia are the main candidates for limb amputations and have a poor life expectancy. Frequently, these patients are not eligible for either surgical or percutaneous interventions aimed at mechanical revascularization. Therefore, new strategies need to b...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-5922.2009.00105.x

    authors: Germani A,Di Campli C,Pompilio G,Biglioli P,Capogrossi MC

    更新日期:2009-01-01 00:00:00

  • miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy.

    abstract:AIM:Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42, Pak1, and miR-30c in the p...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12113

    authors: Raut SK,Kumar A,Singh GB,Nahar U,Sharma V,Mittal A,Sharma R,Khullar M

    更新日期:2015-06-01 00:00:00

  • Circulating CTRP1 Levels Are Increased and Associated with the STOD in Essential Hypertension in Chinese Patients.

    abstract::This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1155/2019/4183781

    authors: Su Z,Tian S,Liang W

    更新日期:2019-06-02 00:00:00

  • Aspirin resistance and compliance with therapy.

    abstract:INTRODUCTION:Aspirin resistance is associated with increased cardiovascular risk in aspirin-treated patients. Poor compliance may explain many cases of "resistance," yet few clinical studies have used objective measurement of therapy compliance. We did so in a case-controlled study. METHODS:We enrolled patients within...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/j.1755-5922.2010.00188.x

    authors: Dawson J,Quinn T,Rafferty M,Higgins P,Ray G,Lees KR,Walters MR

    更新日期:2011-10-01 00:00:00

  • Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects.

    abstract:OBJECTIVES:Endothelial progenitor cells (EPCs) have been shown to participate in the process of vascular repair, thus playing a protective role against cardiovascular disease (CVD). It is known that atherosclerotic risk factors could affect EPC number and function. Advanced glycation end products (AGEs) contribute to t...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/j.1755-5922.2011.00264.x

    authors: Ueda S,Yamagishi S,Matsui T,Noda Y,Ueda S,Jinnouchi Y,Sasaki K,Takeuchi M,Imaizumi T

    更新日期:2012-08-01 00:00:00

  • Impact of Thrombocytopenia on In-Hospital Outcome in Patients Undergoing Percutaneous Coronary Intervention.

    abstract:Background:Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1155/2021/8836450

    authors: Chen Z,Liu Z,Li N,Liu R,Wang M,Wang D,Li C,Li K,Luo F,He Y

    更新日期:2021-01-13 00:00:00

  • Sulforaphane protection against the development of doxorubicin-induced chronic heart failure is associated with Nrf2 Upregulation.

    abstract:BACKGROUND:Doxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose-dependent cardiotoxicity and even progresses to chronic heart failure (CHF). OBJECTIVE:This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX-induced CHF. METHODS:Male ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12277

    authors: Bai Y,Chen Q,Sun YP,Wang X,Lv L,Zhang LP,Liu JS,Zhao S,Wang XL

    更新日期:2017-10-01 00:00:00

  • The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single-Center Study of 409 Patients.

    abstract:AIM:Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12178

    authors: Koektuerk B,Turan CH,Yorgun H,Keskin K,Schoett M,Dahmen A,Gorr E,Yang A,Hoppe C,Horlitz M,Turan RG

    更新日期:2016-06-01 00:00:00

  • Efficacy and safety of a second-generation biodegradable polymer sirolimus-eluting stent: One-year results of the CREDIT 2 trial.

    abstract:AIMS:We performed a multicenter, randomized controlled trial to determine the noninferiority of a novel biodegradable polymer drug-eluting stent (BP-DES), the EXCEL 2 stent, to the first-generation BP-DES, the EXCEL stent. METHODS AND RESULTS:Patients (n = 419) scheduled to undergo percutaneous coronary intervention (...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1111/1755-5922.12327

    authors: Xu K,Han Y,Xu B,Yang Y,Wang G,Li H,Sun Y,Tao L,Wang H,Yuan Z,Liu H,Liu J,Jia Y,Ma G,Fu G,Li X,Li S,Wang S,Pu K,CREDIT 2 Investigators.

    更新日期:2018-06-01 00:00:00

  • Extended dual antiplatelet therapy after acute coronary syndrome in Spain: Results from the EPICOR study.

    abstract:INTRODUCTION:Real-world, country-specific studies of dual antiplatelet therapy (DAPT) duration among survivors of acute coronary syndrome (ACS) are important for improving long-term prognosis. AIMS:To investigate DAPT duration after hospital discharge for ACS in Spain. RESULTS:Data from patients enrolled in the Spani...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,多中心研究

    doi:10.1111/1755-5922.12237

    authors: Bardají A,Leal M,Arrarte V,Garcia-Moll X,Pérez de Isla L,Bueno H

    更新日期:2017-04-01 00:00:00

  • Female Sex as a Thromboembolic Risk Factor in the Era of Nonvitamin K Antagonist Oral Anticoagulants.

    abstract::Sex-specific differences have been definitively demonstrated in cardiovascular (CV) diseases. These differences can also impact on the effects of CV therapies. Female sex is recognized as an independent predictor of thromboembolic risk, particularly in older patients. Most of strokes are due to atrial fibrillation (AF...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1155/2020/1743927

    authors: Gallù M,Marrone G,Legramante JM,De Lorenzo A,Di Daniele N,Noce A

    更新日期:2020-06-18 00:00:00

  • Fenoldopam in critically ill patients with early renal dysfunction. A crossover study.

    abstract:BACKGROUND:Acute kidney injury is a frequent problem among many critically ill patients, commonly in the context of multiple organ failure and decreased renal perfusion. Its presence conveys a poor prognosis. Currently, effective therapeutic interventions are limited and dopaminergic agonists have been suggested as an ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1755-5922.2010.00217.x

    authors: Cobas M,Paparcuri G,De La Pena M,Cudemus G,Barquist E,Varon A

    更新日期:2011-08-01 00:00:00

  • Cilnidipine: a new generation Ca channel blocker with inhibitory action on sympathetic neurotransmitter release.

    abstract::Cilnidipine is a unique Ca(2+) channel blocker with an inhibitory action on the sympathetic N-type Ca(2+) channels, which is used for patients with hypertension in Japan. Cilnidipine has been clarified to exert antisympathetic actions in various examinations from cell to human levels, in contrast to classical Ca(2+) c...

    journal_title:Cardiovascular therapeutics

    pub_type: 历史文章,杂志文章,评审

    doi:10.1111/j.1755-5922.2009.00079.x

    authors: Takahara A

    更新日期:2009-07-01 00:00:00

  • Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus.

    abstract::Atherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/1755-5922.12436

    authors: Tang N,Jiang S,Yang Y,Liu S,Ponnusamy M,Xin H,Yu T

    更新日期:2018-08-01 00:00:00

  • Risk factors for intracranial hemorrhage during vitamin K antagonist therapy in patients with nonvalvular atrial fibrillation: A case-control study.

    abstract:BACKGROUND:Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH. PURPOSE:Search for individual risk factors an...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12458

    authors: Zanella L,Zoppellaro G,Marigo L,Denas G,Padayattil Jose S,Pengo V

    更新日期:2018-10-01 00:00:00

  • Expression of NO Synthase Under Medication with Cyclosporine A, Mycophenolate Mofetil, and Tacrolimus during Development of Transplant Vasculopathy on Rat Cardiac Allograft.

    abstract:OBJECTIVE:The transplant vasculopathy as a sign of chronic graft rejection affects both the epicardial and the intramyocardial arteries of the graft. This is at least partially mediated by NO synthases. The aim of this study was to assess possible protective effects of cyclosporine A (CsA), tacrolimus (FK506), and myco...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12181

    authors: Bogossian H,Frommeyer G,Ninios I,Bandorski D,Seyfarth M,Matzaroglou C,Lemke B,Eckardt L,Zarse M,Kafchitsas K

    更新日期:2016-08-01 00:00:00

  • Therapeutic development in cardiac syndrome X: a need to target the underlying pathophysiology.

    abstract::Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-5922.2008.00070.x

    authors: Lim TK,Choy AJ,Khan F,Belch JJ,Struthers AD,Lang CC

    更新日期:2009-04-01 00:00:00

  • Thiazide-induced hyponatraemia: epidemiology and clues to pathogenesis.

    abstract::Thiazide diuretics are one of the most widely used and cost-effective classes of antihypertensive agents worldwide. Thiazides however have a significant side effect profile and are frequently insufficient to normalize blood pressure alone. Thiazide-induced hyponatraemia (TIH) is a major adverse effect, affecting up to...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-5922.2011.00286.x

    authors: Glover M,Clayton J

    更新日期:2012-10-01 00:00:00

  • Effect on mode of death of heart failure treatment started with bisoprolol followed by Enalapril, compared to the opposite order: results of the randomized CIBIS III trial.

    abstract:BACKGROUND:Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. METHODS:We ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1111/j.1755-5922.2010.00185.x

    authors: Krum H,van Veldhuisen DJ,Funck-Brentano C,Vanoli E,Silke B,Erdmann E,Follath F,Ponikowski P,Goulder M,Meyer W,Lechat P,Willenheimer R,behalf of the CIBIS III Investigators.

    更新日期:2011-04-01 00:00:00

  • Impact of high loading dose of atorvastatin in diabetic patients with renal dysfunction undergoing elective percutaneous coronary intervention: a randomized controlled trial.

    abstract:INTRODUCTION:The effectiveness of statin pretreatment in reducing the incidence of contrast-induced nephropathy (CIN) has been examined in some observational and randomized studies, yielding controversial results. AIM:This study sought to evaluate the role of atorvastatin in prevention of CIN in diabetic patients with...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/1755-5922.12108

    authors: Shehata M,Hamza M

    更新日期:2015-04-01 00:00:00

  • Effects of the recombinant form of the natural human B-type natriuretic peptide and levosimendan on pulmonary hyperventilation and chemosensivity in heart failure.

    abstract:BACKGROUND:The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1755-5922.2011.00297.x

    authors: Bocchi EA,Moura LZ,Issa VS,Cruz F,Carvalho VO,Guimarães GV

    更新日期:2013-04-01 00:00:00

  • Review: Nutriceuticals as antithrombotic agents.

    abstract::Thrombus formation in a disrupted endothelium is influenced not only by the platelet redox state and reactive oxygen and nitrogen species but also by the presence of endogenous or exogenous antioxidants. Thrombus formation in the stenotic arteries is triggered predominantly by attenuated shear stress. Superoxide and n...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-5922.2010.00161.x

    authors: Chakrabarti S,Freedman JE

    更新日期:2010-08-01 00:00:00

  • Secondary prevention in concurrent coronary artery, cerebrovascular, and chronic kidney disease: focus on pharmacological therapy.

    abstract::Patients with coronary artery disease (CAD) commonly have varying degrees of coexisting cerebrovascular disease (CVD) and chronic kidney disease (CKD), and proper management is complicated partly because of a lack of unifying guidelines. The aim of this article is to review the current literature and propose the optim...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1755-5922.2009.00087.x

    authors: Notaro LA,Usman MH,Burke JF,Siddiqui A,Superdock KR,Ezekowitz MD

    更新日期:2009-10-01 00:00:00

  • New Clinical Classification for Ventricular Free Wall Rupture following Acute Myocardial Infarction.

    abstract::Ventricular free wall rupture (FWR) is a catastrophic complication after acute myocardial infarction (AMI). However, patients with FWR die of cardiac tamponade secondary to intrapericardial hemorrhage that can be treated if properly diagnosed. Unfortunately, FWR was still not diagnosed and classified quickly and accur...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1155/2021/1716546

    authors: Gong W,Nie S

    更新日期:2021-01-02 00:00:00

  • The efficacy of glucocorticoids for the prevention of atrial fibrillation, or length of intensive care unite or hospital stay after cardiac surgery: a meta-analysis.

    abstract:AIMS:cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that has been suggested playing a causative role in the development of perioperative atrial fibrillation (POAF). The goal of this meta-analysis was to determine the efficacy of glucocorticoid prophylaxis in ...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,meta分析,评审

    doi:10.1111/1755-5922.12062

    authors: Liu C,Wang J,Yiu D,Liu K

    更新日期:2014-06-01 00:00:00

  • A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects.

    abstract:AIMS:We investigated the relative pharmacokinetics, pharmacodynamics, and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab following injection at three different sites. METHODS:Sixty healthy subjects (39 male, 21 female; age 20-45 years) were randomized to receive a single subcu...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/1755-5922.12093

    authors: Lunven C,Paehler T,Poitiers F,Brunet A,Rey J,Hanotin C,Sasiela WJ

    更新日期:2014-12-01 00:00:00

  • Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis.

    abstract:AIM:To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement. METHODS:A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared a...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,meta分析,评审

    doi:10.1111/1755-5922.12230

    authors: Zhang J,Tian L,Huang J,Huang S,Chai T,Shen J

    更新日期:2017-02-01 00:00:00

  • Treatment of secondary pulmonary hypertension with bosentan after left ventricular assist device implantation.

    abstract:INTRODUCTION:Secondary pulmonary hypertension (PH) and right ventricular dysfunction are common and associated with poor prognosis in HF patients with left ventricular assist devices (LVADs). The role of pulmonary vasodilator therapy for these patients is currently unclear. AIMS:We sought to evaluate the safety and cl...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章

    doi:10.1111/1755-5922.12111

    authors: LaRue SJ,Garcia-Cortes R,Nassif ME,Vader JM,Ray S,Ravichandran A,Rasalingham R,Silvestry SC,Ewald GA,Wang IW,Schilling JD

    更新日期:2015-04-01 00:00:00

  • Inhibitors of advanced glycation end products (AGEs): potential utility for the treatment of cardiovascular disease.

    abstract::Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, stroke, blindness, and end-stage renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Recent clinical studies have substantiated the concept of "hyperglycemic...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/j.1527-3466.2007.00038.x

    authors: Yamagishi S,Nakamura K,Matsui T,Ueda S,Noda Y,Imaizumi T

    更新日期:2008-04-01 00:00:00

  • Microsomal transfer protein inhibitors, new approach for treatment of familial hypercholesterolemia, review of the literature, original findings, and clinical significance.

    abstract::The genetic causes of cholesterol metabolism disorders usually lead to premature atherosclerosis. The most well recognized genetically caused hypercholesterolemia is familial hypercholesterolemia. Although the disease is well known, as the discovery of low-density lipoprotein receptor, the classical treatment with lip...

    journal_title:Cardiovascular therapeutics

    pub_type: 杂志文章,评审

    doi:10.1111/1755-5922.12105

    authors: Kolovou G,Vasiliadis I,Gontoras N,Kolovou V,Hatzigeorgiou G

    更新日期:2015-04-01 00:00:00