Abstract:
:Diabetes and CYP2C19 loss of function (LOF) alleles are associated with the variable antiplatelet activity of the prodrug clopidogrel. We conducted a randomized trial (NCT03613857) to compare the combined and individualized effects of diabetes and CYP2C19 polymorphisms on the antiplatelet reactivity of clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Patients (948, 1 year follow-up 943) were randomly allocated in a 1:1 ratio to receive either clopidogrel or ticagrelor, after PCI; patients were subdivided into 8 subgroups according to the diabetes and/or CYP2C19 allele status. The study outcomes were recurrent ACS, maximum platelet aggregation (MPA), high platelet reactivity index (PRI), and incidence of major bleeding events. Diabetic patients with LOF alleles taking clopidogrel had the highest recurrent ACS rate (6 of 33 patients) versus all other study groups (P < 0.05). However, both drugs had similar proportions of recurrent ACS in all other subgroups. Similarly, both PRI and MPA were significantly higher in the diabetic patients having LOF alleles and receiving clopidogrel versus all their study groups (P < 0.05). Nevertheless, ticagrelor caused higher rates of major bleeding versus clopidogrel (P < 0.001). PCI-treated ACS patients with diabetes and CYP2C19 LOF alleles are at a higher risk of recurrent ACS and high PRI/MPA, when treated with clopidogrel versus ticagrelor, but almost comparable outcomes are recorded in the absence of 1 or the 2 risk factors.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Mohareb MW,AbdElghany M,Zaki HF,El-Abhar HSdoi
10.1097/FJC.0000000000000881subject
Has Abstractpub_date
2020-10-01 00:00:00pages
478-488issue
4eissn
0160-2446issn
1533-4023journal_volume
76pub_type
杂志文章abstract::The effects of potent coronary vasodilator, 2- phenylaminoadenosine (CV-1808), on coronary circulatory failure and thromboxane (TX) A2 release were studied during coronary occlusion (for 60 min) and subsequent reperfusion (for 60 min) in anesthetized dogs. During coronary reperfusion, reactive hyperemic response was a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198405000-00011
更新日期:1984-05-01 00:00:00
abstract::Since the end of 1976 ten orally active converting enzyme inhibitors [SQ 14,225 (captopril), MK 421 (enalapril), MK 422, MK 521 (lysinopril), RHC 3659, CGS 13945, CGS 13928C, CGS 14824A, Hoe 498, S 9490-3, and Ro 31-2848] have been evaluated by our group in normal volunteers. Their ability to blunt the pressor respons...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198507001-00002
更新日期:1985-01-01 00:00:00
abstract::The in vivo renal microvascular effects of three antihypertensive drugs: nitrendipine, a calcium entry blocker, and two direct-acting vasodilator agents, hydralazine and minoxidil, were compared. The dilator responses of pre- and postglomerular vessels were directly observed after the topical or intravenous administra...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199004000-00002
更新日期:1990-04-01 00:00:00
abstract::Apoptosis, a genetically controlled programmed cell death, has been found to play a role in ischemic reperfusion injury in several animal species including rats and rabbits. To examine whether this also is true for other animals, a surgically relevant model was established using an isolated in situ swine heart. Hearts...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200011000-00009
更新日期:2000-11-01 00:00:00
abstract:ABSTRACT:Atrial tachypacing is an accepted model for atrial fibrillation (AF) in large animals and in cellular models. Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) provide a novel, human source to model cardiovascular diseases. Here we investigated whether optogenetic tachypacing of atrial-lik...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000951
更新日期:2020-12-22 00:00:00
abstract::Inhibition of plasma angiotensin II generation does not fully explain the chronic hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. Therefore, the pattern of tissue ACE inhibition in rats was studied after oral administration of perindopril, a new ACE inhibitor. Tissue ACE was measured by quantita...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812000-00013
更新日期:1988-12-01 00:00:00
abstract::Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199200111-00004
更新日期:1992-01-01 00:00:00
abstract::Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::The dependency of arteriolar tone on calcium influx was studied in 11 patients with essential hypertension (EHT) and compared to 11 age-matched normotensive (NT) subjects by measuring the forearm blood flow (FAF) response to intraarterial infusion of the calcium channel blocker verapamil (Verap) and the nonspecific va...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Lacidipine is a clinically active, antihypertensive calcium antagonist of the 1,4 dihydropyridine (DHP) class. It is also capable of vascular protection when administered (prophylactically and therapeutically) at nonsustained antihypertensive doses to salt-sensitive Dahl-S rats: useful animal models for studying the v...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200204000-00002
更新日期:2002-04-01 00:00:00
abstract::Heart failure (HF) is characterized by activation of both neurohumoral and sympathetic nervous systems. Specifically, HF is associated with increases in vasopressin (VP) and endothelin (ET) and in arterial baroreflex dysfunction. Hypothesis was that central ET-1 potentiates VP secretion in HF due to impaired pressor r...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200207000-00010
更新日期:2002-07-01 00:00:00
abstract::There is general agreement that the sympathetic nervous system is involved in the development of hypertension in spontaneously hypertensive rats (SHR). However, in a previous study we established that chronic administration of the selective alpha 1-adrenoceptor antagonist terazosin to SHR failed to prevent this phenom...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199305000-00015
更新日期:1993-05-01 00:00:00
abstract::The effects of nitrendipine, a new antihypertensive agent, have been examined using the isolated rabbit aortic strip stimulated with either noradrenaline (1.7 X 10(-8) - 1.7 X 10(-5) mol/L) or potassium (22.7-52.7 mmol/L). Nifedipine, verapamil, phentolamine, papaverine, and minoxidil were used as reference compounds....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::Therapeutic response to angiotensin-converting enzyme (ACE) inhibitors was reported to be better related to tissular than to circulating levels of ACE inhibition, especially during chronic therapy. We studied the relations between plasma concentrations of angiotensin I (AI), plasma renin activity (PRA), angiotensin II...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199607000-00003
更新日期:1996-07-01 00:00:00
abstract::The pharmacologic profile of SK-1080, a nonpeptide AT1-selective angiotensin-receptor antagonist, was investigated by receptor-binding studies, functional in vitro assays with rabbit and rat aorta, and in vivo experiments in pithed rats. SK-1080 inhibited the specific binding of [125I]-[Sar1, Ile8]-angiotensin II to h...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199903000-00004
更新日期:1999-03-01 00:00:00
abstract::The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting beta-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 microg/ kg/min. Each infusion wa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199907000-00012
更新日期:1999-07-01 00:00:00
abstract::The acute effects of daunomycin on the mechanical and energetic outputs of rabbit papillary muscles have been examined at 27 degrees C using a myothermic technique. Contrary to expectations, daunomycin, in concentrations ranging from 10 to 160 micrograms/ml, acted as a positive inotropic agent in terms of peak stress ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198505000-00023
更新日期:1985-05-01 00:00:00
abstract::The antihypertensive effect of the combination of ketanserin, a new antiserotonergic agent, and thiazide has been evaluated in 35 patients with arterial hypertension of mild to moderate degree in the greater than 50-year-old age group. Twenty patients were given ketanserin (20 mg) + hydrochlorothiazide (25 mg) (treatm...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1987-01-01 00:00:00
abstract::Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ET(A)/ET(B)) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU13525...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00074
更新日期:2000-11-01 00:00:00
abstract::We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200312001-00013
更新日期:2003-12-01 00:00:00
abstract::Reperfusion of ischemic myocardium is accompanied by intracellular Ca overload, leading to cardiac dysfunction. However, the mechanisms underlying intracellular Ca overload have yet to be fully elucidated. The mechanism may involve the activation of store-operated Ca entry, which is primarily mediated through the tran...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000566
更新日期:2018-04-01 00:00:00
abstract::The comparative contributions of arachidonic acid (AA) metabolites and 5-hydroxytryptamine (5-HT) to the delay of reperfusion and rate of reocclusion after coronary thrombolysis with streptokinase were assessed in dogs using (a) single TXA2 synthase inhibition; (b) single 5-HT2-receptor blockade; (c) dual TXA2 synthas...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199301000-00009
更新日期:1993-01-01 00:00:00
abstract::Endothelin-1 (ET-1) is synthesized and secreted by cardiomyocytes and induces cardiac hypertrophy. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a lipid-activated nuclear receptor that negatively regulates the vascular inflammatory gene response by interacting with transcription factors, such as nuc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166303.33313.01
更新日期:2004-11-01 00:00:00
abstract::The functional and anatomical abnormalities of the right ventricle may occur in hypertensive patients with left ventricular hypertrophy (LVH). The present study was designed to assess the functional and structural changes in both left and right ventricles induced by chronic antihypertensive therapy. Doppler and standa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199117002-00039
更新日期:1991-01-01 00:00:00
abstract::We produced transgenic mice overexpressing Na+/ H+ exchanger as a model of salt-sensitive hypertension and reported that dietary salt loading elevates blood pressure in these transgenic mice. We speculate that this blood pressure elevation may be attributed to the elevation of intraarterial smooth muscle Ca2+ concentr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00024
更新日期:2000-03-01 00:00:00
abstract::Cardiovascular effects of Nifekalant were examined using halothane-anesthetized dogs, and its proarrhythmic potential was estimated with chronic complete atrioventricular block dogs. Nifekalant was intravenously administered to the halothane-anesthetized dogs in three doses of 0.03, 0.3, and 3 mg/kg/10 minutes with a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200405000-00015
更新日期:2004-05-01 00:00:00
abstract::Activity in central sympathetic pathways can be modified by stimulating central alpha 2-adrenoceptors, e.g., with clonidine, or, more recently, by stimulating central 5-hydroxytryptamine (5-HT1A) receptors. Stimulation of 5-HT1A receptors causes central sympathoinhibition and an increase in cardiac vagal drive, which ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract::Severe pulmonary arterial hypertension (PAH) is characterized by clustered proliferation of endothelial cells (ECs) in the lumina of small size pulmonary arteries resulting in concentric obliteration of the lumina and formation of complex vascular structures known as plexiform lesions. This debilitating disease occurs...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181f9ea8d
更新日期:2010-12-01 00:00:00
abstract::We studied the inotropic and possible antioxidant effects of levosimendan in human atrial strips, before and after induction of oxidative stress induced by H2O2. Levosimendan (10(-9) to 10(-6) M) increased contractions induced by electrical stimulation (ES) in human atrial strips. The maximal positive inotropic effect...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318123fbf9
更新日期:2007-10-01 00:00:00