Abstract:
OBJECTIVES:The goal of this study was to evaluate the effect of smoking on the pharmacokinetics and pharmacodynamics (PD) of clopidogrel and prasugrel therapy. BACKGROUND:Major randomized trial data demonstrated that nonsmokers experience less or no benefit from clopidogrel treatment compared with smokers (i.e., the "smokers' paradox"). METHODS:PARADOX was a prospective, randomized, double-blind, double-dummy, placebo-controlled, crossover study of objectively assessed nonsmokers (n = 56) and smokers (n = 54) with stable coronary artery disease receiving aspirin therapy. Patients were randomized to receive clopidogrel (75 mg daily) or prasugrel (10 mg daily) for 10 days and crossed over after a 14-day washout. PD was assessed by using VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein phosphorylation assays. Clopidogrel and prasugrel metabolite levels, cytochrome P450 1A2 activity, CYP2C19 genotype, and safety parameters were determined. RESULTS:During clopidogrel therapy, device-reported inhibition of platelet aggregation (IPA) trended lower in nonsmokers than smokers (least squares mean treatment difference ± SE: 7.7 ± 4.1%; p = 0.062). Device-reported IPA was significantly lower in clopidogrel-treated smokers than prasugrel-treated smokers (least squares mean treatment difference: 31.8 ± 3.4%; p < 0.0001). During clopidogrel therapy, calculated IPA was lower and P2Y12 reaction units and vasodilator-stimulated phosphoprotein phosphorylation and platelet reactivity index were higher in nonsmokers than in smokers (p = 0.043, p = 0.005, and p = 0.042, respectively). Greater antiplatelet effects were present after prasugrel treatment regardless of smoking status (p < 0.001 for all comparisons). CONCLUSIONS:PARADOX demonstrated lower clopidogrel active metabolite exposure and PD effects of clopidogrel in nonsmokers relative to smokers. Prasugrel was associated with greater active metabolite exposure and PD effects than clopidogrel regardless of smoking status. The poorer antiplatelet response in clopidogrel-treated nonsmokers may provide an explanation for the smokers' paradox. (The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease; NCT01260584).
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Gurbel PA,Bliden KP,Logan DK,Kereiakes DJ,Lasseter KC,White A,Angiolillo DJ,Nolin TD,Maa JF,Bailey WL,Jakubowski JA,Ojeh CK,Jeong YH,Tantry US,Baker BAdoi
10.1016/j.jacc.2013.03.037subject
Has Abstractpub_date
2013-08-06 00:00:00pages
505-12issue
6eissn
0735-1097issn
1558-3597pii
S0735-1097(13)01478-2journal_volume
62pub_type
杂志文章,多中心研究,随机对照试验abstract:BACKGROUND:Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. OBJECTIVES:This study sought to investigate the association of exPH with ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2019.10.048
更新日期:2020-01-07 00:00:00
abstract::Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), platelet aggregation and procoagulant effect (in vitro) as compared with ionic contrast media. To study these effects in vivo, 30 consecutive patients undergoing routine angiography were prospectively randomized to three groups of 10 p...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0735-1097(91)90643-n
更新日期:1991-06-01 00:00:00
abstract::Alterations in the blood radioactivity affect ventricular volume calculations using count-based radionuclide ventriculography. To study this phenomenon, the effect of time, posture and supine exercise on blood radioactivity, red blood cell count and splenic radioactivity was evaluated. The red blood cell count, and bl...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(84)80178-3
更新日期:1984-05-01 00:00:00
abstract:BACKGROUND:There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline. OBJECTIVES:This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Inte...
journal_title:Journal of the American College of Cardiology
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doi:10.1016/j.jacc.2019.09.041
更新日期:2019-11-26 00:00:00
abstract:OBJECTIVES:The aim of the present study was to verify whether angiotensin-II converting enzyme (ACE) inhibition is also effective in preventing relapses of lone atrial fibrillation (LAF), that is, in the absence of hypertension and/or heart disease. BACKGROUND:Several studies have shown that ACE inhibitors are effecti...
journal_title:Journal of the American College of Cardiology
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更新日期:2009-01-06 00:00:00
abstract:OBJECTIVES:This study sought to determine whether circadian patterns in ventricular arrhythmias (VAs) occur in a current primary prevention defibrillator (implantable cardioverter-defibrillator [ICD]) population. BACKGROUND:Cardiovascular events, including VAs, demonstrate biorhythmic periodicity. METHODS:We tested f...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2013.11.072
更新日期:2014-06-24 00:00:00
abstract:OBJECTIVES:Nonischemic contractile segmental performance was characterized by the end-systolic pressure-length and pressure-thickness relations during regional ischemia induced by proximal left anterior descending and left circumflex coronary artery occlusions. BACKGROUND:The increases in shortening and thickening of ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(94)90189-9
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVES:The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio). BACKGROUND:While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(98)00564-6
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVES:This study investigated the ability of QT duration, QT dispersion (QTD) and clinical diagnostic criteria to correctly identify genetically documented LQT1 type long QT syndrome (LQTS) patients, and to separate symptomatic and asymptomatic LQT1 patients. BACKGROUND:Ventricular repolarization has played an es...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(98)00248-4
更新日期:1998-08-01 00:00:00
abstract:OBJECTIVES:We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. BACKGROUND:The AFFIRM study showed that atrial fibrillation (AF) can be treated effect...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.jacc.2003.11.032
更新日期:2004-04-07 00:00:00
abstract::Humans are prone to sodium overload and potassium depletion. This electrolyte imbalance is important in the pathogenesis of cardiovascular disease and sudden cardiac death. Avoiding hypokalemia is beneficial in several cardiovascular disease states including acute myocardial infarction, heart failure, and hypertension...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2003.06.021
更新日期:2004-01-21 00:00:00
abstract:OBJECTIVES:The study was done to characterize the electrocardiographic and electrophysiologic features of focal atrial tachycardia originating at the mitral annulus (MA). BACKGROUND:Though the majority of left atrial tachycardias originate around the ostia of the pulmonary veins, only isolated reports have described f...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(03)00484-4
更新日期:2003-06-18 00:00:00
abstract:OBJECTIVES:The objective of this study was to compare the cerebral embolic load of filter-protected versus proximal balloon-protected carotid artery stenting (CAS). BACKGROUND:Randomized trials comparing filter-protected CAS with carotid endarterectomy revealed a higher periprocedural stroke rate after CAS. Proximal b...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2011.11.035
更新日期:2012-04-10 00:00:00
abstract::Hemodynamic stress testing was performed in four calves with a chronically implanted left ventricular assist device consisting of a double-valved pump interposed between the left ventricular apex and the descending thoracic aorta. The device was powered either pneumatically (n = 1) or with a transcutaneous energy tran...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(91)90521-a
更新日期:1991-12-01 00:00:00
abstract:OBJECTIVES:To assess whether 15-(p-[iodine-123] iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP) imaging can identify previous ischemic areas, BMIPP SPECT was performed in patients with acute chest pain to compare its findings with those of technetium-99m-tetrofosmin (tetrofosmin) SPECT and coronary angiography. B...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(01)01634-5
更新日期:2001-12-01 00:00:00
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/j.jacc.2014.01.046
更新日期:2014-05-20 00:00:00
abstract:OBJECTIVES:We tested the hypothesis that CD40 ligand (CD40L) induces a prothrombotic state by enhancing oxidative stress. BACKGROUND:Patients with hypercholesterolemia show an ongoing prothrombotic state, but the underlying mechanism is still unclear. METHODS:Circulating levels of the soluble form of CD40L (sCD40L), ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2004.09.047
更新日期:2005-01-04 00:00:00
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更新日期:2017-01-17 00:00:00
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更新日期:2002-06-05 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.jacc.2004.05.086
更新日期:2004-11-02 00:00:00
abstract::Percutaneous balloon valvuloplasty was attempted in 10 newborn infants with critical aortic valve stenosis and severe congestive heart failure. Three had a very small left ventricle and aortic anulus. In one infant, the aortic valve could not be passed, and in another infant, a technical error resulted in severe valvu...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
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更新日期:1985-07-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 指南,杂志文章
doi:10.1016/0735-1097(91)90556-o
更新日期:1991-11-01 00:00:00
abstract:OBJECTIVES:This study sought to develop quality indicators (QIs) for outpatient management of adult congenital heart disease (ACHD) patients. BACKGROUND:There are no published QIs to promote quality measurement and improvement for ACHD patients. METHODS:Working groups of ACHD experts reviewed published data and Unite...
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doi:10.1016/j.jacc.2013.07.099
更新日期:2013-12-10 00:00:00
abstract:OBJECTIVES:The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation. BACKGROUND:Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthe...
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pub_type: 杂志文章
doi:10.1016/j.jacc.2011.08.066
更新日期:2012-01-10 00:00:00
abstract:OBJECTIVES:This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND:Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique de...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1996-01-01 00:00:00
abstract:OBJECTIVES:Our goal was to compare histologically the mechanisms producing congenital complete heart block in normally structured hearts and in hearts with isomerism of the atrial appendages. BACKGROUND:It is known that several different histologic patterns can underscore the existence of congenital complete heart blo...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(92)90191-o
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to determine the incidence and significance of second- or third-degree heart block among patients with inferior myocardial infarction treated with thrombolytic therapy. BACKGROUND:Data from the prethrombolytic era suggest that heart block occurs in approximately 20% of patients wit...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/0735-1097(92)90004-7
更新日期:1992-09-01 00:00:00
abstract::The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Trial randomized 368 patients with symptoms and signs of acute myocardial infarction of less than 6 h duration to either conventional care or 1.5 million units of intravenous streptokinase. The mean time to randomization was 209 min and 52...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0735-1097(88)90197-0
更新日期:1988-04-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI). BACKGROUND:Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studi...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2008.12.044
更新日期:2009-04-14 00:00:00