Abstract:
PURPOSE:Clopidogrel is a thienopyridine prodrug that inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients receiving a stent implant in carotid, vertebral, or cranial arteries. The influence of cytochrome P-450 (CYP) 2C19 on the response to clopidogrel has been widely studied; however, the effect of other genes involved in clopidogrel absorption and metabolism has not been established in this cohort of patients. METHODS:This observational retrospective study assessed the antiplatelet response and the prevalence of hemorrhagic or ischemic events after percutaneous neurointervention in clopidogrel-treated patients, related to 35 polymorphisms in the genes encoding the clopidogrel-metabolizing enzymes (CYP2C19, CYP1A2, CYP2B6, CYP2C9, CYP2C9, CYP3A4, CYP3A5, carboxylesterase-1 [CES1], and paraoxonase-1 [PON1]), P-glycoprotein transporter (ABCB1), and platelet receptor P2Y12. Polymorphisms were analyzed by quantitative real-time polymerase chain reaction and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Antiplatelet response was documented with the VerifyNow system (Accriva, San Diego, California). FINDINGS:We confirmed that CYP2C19 is the most important enzyme involved in clopidogrel response. The carriage of the CYP2C19*2 allele was strongly associated with hyporesponse to clopidogrel, while the CYP2C19*17 allele was a protective factor for the development of ischemic events (odds ratio = 0.149; P = 0.002) but a risk factor for bleeding (odds ratio = 3.60; P = 0.038). Patients carrying ABCB1 mutated alleles showed lower aggregation values, suggesting that clopidogrel absorption is influenced by P-glycoprotein. In fact, the percentage of responders was significantly higher in the group carrying the mutated haplotype compared to the wild type (80.8% vs 43.3%; P = 0.009). Patients with the CES1 G143E C/T genotype showed a considerably lower, aggregation value versus wild-type patients, although the difference was not significant likely due to the small sample size (59.0 [21.2] vs 165.2 [86.0] PRU; P = 0.084), which suggests an increased active metabolite formation. No relationship was found between polymorphisms in other CYP genes, PON1, or P2RY12 and response to clopidogrel in patients subjected to neurointervention procedures. IMPLICATIONS:Therapeutic guidelines recommend that CYP2C19 intermediate and poor metabolizers with acute coronary syndromes undergoing percutaneous coronary intervention receive an alternative antiplatelet therapy; however, genotype-guided therapy is not a standard recommendation for neurovascular conditions. This is the first study to carry out a joint analysis of CYP2C19 and other genes involved in clopidogrel treatment in patients receiving percutaneous neurointervention. Our findings support routine genotyping in clopidogrel-treated patients. Moreover, we encourage considering an alternative antiplatelet therapy in CYP2C19 intermediate, poor and ultrarapid metabolizers. Additionally, ABCB1 polymorphisms could be considered for a better pharmacogenetic approach.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Saiz-Rodríguez M,Belmonte C,Caniego JL,Koller D,Zubiaur P,Bárcena E,Romero-Palacián D,Eugene AR,Ochoa D,Abad-Santos Fdoi
10.1016/j.clinthera.2019.04.037subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1199-1212.e2issue
6eissn
0149-2918issn
1879-114Xpii
S0149-2918(19)30240-1journal_volume
41pub_type
杂志文章abstract:OBJECTIVE:This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. BACKGROUND:Prolonged treatment with oral NAC has...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/S0149-2918(00)88479-9
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Despite favorable evidence from clinical trials for single-dose palonosetron versus other commercially available 5-HT(3)-receptor antagonists for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV), clinical comparative data are scarce from hospital outpatient settings, where these antiemetic ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.04.009
更新日期:2011-04-01 00:00:00
abstract::In two multicenter, double-blind studies, ciclopirox olamine cream 1% was compared with either its cream vehicle or with 1% clotrimazole cream for the treatment of patients with tinea pedis. Evaluations were made before treatment, weekly for four weeks during treatment, and for two weeks posttreatment. Ciclopirox olam...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute ep...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(97)80120-8
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Dual antiplatelet therapy with a thienopyridine (ticlopidine or clopidogrel) and aspirin is used to reduce the risk of late stent thrombosis and complications (myocardial infarction [MI] and death) after placement of a drug-eluting stent (DES). OBJECTIVE:This article reviews available clinical efficacy and ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.01.003
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2019.05.019
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Seasonal allergic rhinitis (SAR) is an allergen-induced inflammatory reaction that occurs during periods of high pollen count. Current treatments for SAR include allergen avoidance, systemic antihistamines, and steroidal and nonsteroidal intranasal sprays. Olopatadine is a selective antihistamine and an inhi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2009.01.016
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.10.018
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Physiologic changes of aging may affect processes of drug absorption and distribution, in some cases necessitating age-dependent dose adjustment. OBJECTIVE:The possibility of age dependence in the pharmacokinetic behavior and tolerability of levormeloxifene was investigated in a single-center, open-label st...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(01)80030-8
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES:Two studie...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2007.03.018
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE:The objective of this study was to evaluate the cost-effect...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.12.011
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that increases blood glucose and is a drug target for treatment of type 2 diabetes. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for w...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.06.004
更新日期:2011-07-01 00:00:00
abstract::Encapsulation affects the virulence and survival of anaerobic bacteria and their protection from phagocytosis. More encapsulated Bacteroides strains and anaerobic and facultative gram-positive cocci are isolated from patients with clinical infections than from healthy people. The pathogenicity of Bacteroides, Fusobact...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::Serum creatinine and beta 2-microglobulin levels, endogenous creatinine clearance, the urinary beta 2-microglobulin excretion rate, and urinary protein levels were monitored serially in 29 patients with duodenal ulcers randomly allocated to receive eight weeks of treatment with cimetidine, ranitidine, or an antacid. A...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Rufinamide is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients aged ≥4 years. OBJECTIVES:The primary purpose of this study was to compare the relative bioavailability and other pharmacokinetics of rufinamide administered as a 400-mg tablet formulation (r...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2011.01.016
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.02.009
更新日期:2015-05-01 00:00:00
abstract::This paper presents a state-of-the-art review of oral contraceptives (OCs), termed one of the epochal developments of modern times. OCs have had both direct and indirect influences on moral, social, and cultural values and on the interaction of population resources and the environment. In recent years there has been...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Many patients with asthma require an inhaled long-acting beta(2)-agonist (LABA) in addition to an inhaled corticosteroid to adequately control their disease. OBJECTIVE:The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate (SFC) hydrofluoroalkane...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2007.07.021
更新日期:2007-07-01 00:00:00
abstract::Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in T cells and monocytes in vitro by inhibiting posttranscriptional modification of the virus. An initial randomized, placebo-controlled cl...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(97)80045-8
更新日期:1997-09-01 00:00:00
abstract:PURPOSE:Surgery, radiotherapy, and chemotherapy are the mainstays of cervical cancer treatment. Many patients receive multiple treatment modalities, each with its own long-term effects. Given the high 5-year survival rate for cervical cancer patients, evaluation and improvement of long-term quality of life are essentia...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.11.013
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy. METHODS:A retrospec...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.09.012
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery. Adverse events associated with IFN alfa-2b use are primarily constitutional symptoms. However, hypertriglyceridemia requiring treatment has been reported. ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.12.002
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Patients' adherence to antiosteoporotic drug therapy is essential to prevent fracture and complications of osteoporosis over the long term. The guidance given in treating osteoporosis can potentially enhance adherence. OBJECTIVE:This study was conducted to compare adherence to osteoporosis regimens by patie...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.05.019
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:The goal of this health economic analysis was to asses the cost-effectiveness of a fixed combination of aspirin plus extended-release dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy for prevention of recurrent ischemic stroke. BACKGROUND:The second European Stroke Prevention Study (ASA/...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)80041-7
更新日期:2000-03-01 00:00:00
abstract::In this open-label, randomized, cross-over study, 12 healthy subjects received four doses of a new sustained-release formulation of diltiazem hydrochloride for six consecutive days. Blood samples were drawn on days 5 and 6 for determination of plasma diltiazem and desacetyldiltiazem levels. The peak concentrations aft...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-03-01 00:00:00
abstract::The US population is multiethnic in composition: many languages thrive, and Spanish is the second most frequently spoken language. The Hispanic population is one of the fastest growing ethnic groups in the United States. The majority of Hispanics speak Spanish at home (63%), and a significant proportion speak little o...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/0149-2918(95)80054-9
更新日期:1995-07-01 00:00:00
abstract::The increasing worldwide recognition of the deleterious sequelae of Chlamydia trachomatis urogenital tract infections makes rapid, inexpensive diagnostic tests a high priority. Cell culture, still the standard for all other methods, is only 90% sensitive. Direct fluorescent antibody (FA) tests use highly specific mono...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::The effects of long-term aprindine administration on cardiac function were clinically investigated in seven patients with supraventricular or ventricular arrhythmias associated with organic heart disease. Three patients had normal cardiac function and four had various degrees of cardiac dysfunction before treatment wi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Inhibitors of platelet glycoprotein (GP) IIb-IIIa have been demonstrated to be effective in controlling acute cardiac complications in patients presenting with acute ischemic coronary syndromes (AICS). Since patients with atherosclerotic coronary vascular disease may present with AICS on multiple occasions, it is impo...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)88273-9
更新日期:1999-01-01 00:00:00