Abstract:
AIMS:To analyse clinical outcomes with direct oral anticoagulants in patients with atrial fibrillation according to geographic region. METHODS:We systematically searched MEDLINE, CENTRAL, websites of regulatory agencies, clinical trials registers and conference proceedings for randomized controlled trials of direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) against warfarin for prophylaxis of stroke and systemic embolic events (SEE) in patients with atrial fibrillation (AF). Two investigators independently extracted data. Relative risks of stroke and SEE as well as major bleeding depending on geographic region were estimated using a random effect meta-analysis. RESULTS:Five trials in 72 963 patients were analysed; 32 089 (44%) patients were recruited in Europe (Western Europe: 13 676; Eastern Europe: 18 413). We found significant subgroup differences for stroke/SEE depending on the geographic region (interaction P = 0.003; I(2) 88.5%), with a neutral effect of the DOAC vs. warfarin in Europe [relative risk (RR) 0.97, 95% confidence interval (CI) 0.85-1.11, I(2) 0%] and a significant reduction of stroke/SEE in other regions including North America, Latin America and Asia-Pacific/other (RR 0.72, 95% CI 0.63-0.83, I(2) 33%). There was a similar reduction in risk of major bleeding in Europe (RR 0.82, 95% CI 0.73-0.92, I(2) 0%) and in other regions (RR 0.86, 95% CI 0.72-1.02, I(2) 78%). CONCLUSION:The DOAC did not provide additional benefit in reducing the risk of stroke/SEE compared with warfarin in European patients with AF, but were generally associated with a lower bleeding tendency than warfarin regardless of geographic region.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Gómez-Outes A,Terleira-Fernández AI,Calvo-Rojas G,Suárez-Gea ML,Vargas-Castrillón Edoi
10.1111/bcp.13005subject
Has Abstractpub_date
2016-09-01 00:00:00pages
633-44issue
3eissn
0306-5251issn
1365-2125journal_volume
82pub_type
杂志文章,meta分析,评审abstract:AIMS:The aims of this study were to determine the effects of the nonsteroidal, selective aromatase inhibitor, anastrozole, at steady-state concentrations, on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not anastrozole alone has any anticoagulant activity. METHODS:This was a randomiz...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.2001.01358.x
更新日期:2001-05-01 00:00:00
abstract:AIMS:To determine the paediatric licensing status in the USA, UK, Australia and New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to assess the importance of those medicines to paediatric practice. METHODS:The medicines granted a patent extension in the USA as of 10 November 2003 were iden...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02327.x
更新日期:2005-06-01 00:00:00
abstract:AIMS:To assess the antihistaminic activity of levocetirizine and fexofenadine 2 h and 24 h after drug administration using facial thermography and to compare the results with those using well-established parameters of antihistaminic activity in the nose and skin. METHODS:This was a randomized, double-blind, three-trea...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2006.02647.x
更新日期:2006-08-01 00:00:00
abstract::1. Lisinopril and enalapril were administered as 2.5 mg single doses and as eight single daily 2.5 mg doses to separate groups of six patients with chronic renal failure. Patients were receiving regular haemodialysis. 2. In the absence of haemodialysis, the decline in plasma concentrations of lisinopril and enalaprila...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05319.x
更新日期:1988-12-01 00:00:00
abstract:AIMS:To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS:The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: in...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.0306-5251.2001.01486.x
更新日期:2001-11-01 00:00:00
abstract:AIM:To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODS:Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13127
更新日期:2017-02-01 00:00:00
abstract::1 Fifty-two patients who had been treated for essential hypertension for at least 5 years with once-a-day pindolol alone or in combination with a diuretic participated in a strenuous exercise programme. The 24 h antihypertensive efficacy of once-a-day pindolol was shown in blood pressure readings made before the intak...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01443.x
更新日期:1982-05-01 00:00:00
abstract::A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determine...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05132.x
更新日期:1985-12-01 00:00:00
abstract:AIMS:Several studies have reported the under-representation of women in clinical trials, thereby challenging the external validity of the benefit/risk assessments of launched drugs. Our aim was to determine the extent to which women have been included in clinical trials used for drug registration and to analyse the fra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13497
更新日期:2018-04-01 00:00:00
abstract::Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14031
更新日期:2019-09-01 00:00:00
abstract:AIMS:The aim of this study was to use data from an experimental induced blood stage malaria clinical trial to characterize the antimalarial activity of the new compound Actelion-451840 using pharmacokinetic/pharmacodynamic (PK/PD) modelling. Then, using simulations from the model, the dose and dosing regimen necessary ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12962
更新日期:2016-08-01 00:00:00
abstract:AIMS:Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS:A randomized, two-way crossover stud...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2009.03564.x
更新日期:2010-02-01 00:00:00
abstract:AIMS:To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects. METHODS:Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (+/-10 years) and body weight (+/-20%) and administere...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/j.1365-2125.2005.02340.x
更新日期:2005-05-01 00:00:00
abstract::The plasma concentration-response relationships of oral and intravenous pindolol and propranolol have been studied in a group of eight healthy male subjects who received each dosage form in a randomized single-blind cross-over manner. Despite similar elimination half-lives, the duration of action of pindolol was longe...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1985.tb05088.x
更新日期:1985-10-01 00:00:00
abstract::Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dos...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12789
更新日期:2016-03-01 00:00:00
abstract::1 Evidence concerning the convulsant effects of non-monoamine oxidase inhibitor antidepressant drugs has been reviewed. 2 Mianserin is convulsant in therapeutic doses but seizures have not been reported following overdose. 3 The convulsant effects of mianserin are probably no greater than for other non-monoamine oxida...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb05878.x
更新日期:1983-01-01 00:00:00
abstract::1. We have compared acute gastric bleeding caused by a new slow release preparation of indomethacin (indomethacin Continus) with that caused by aspirin and other indomethacin preparations. 2. In a randomized crossover study, blood loss into timed gastric aspirates was determined in 20 healthy volunteers after receivin...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1988.tb03382.x
更新日期:1988-08-01 00:00:00
abstract::1 The heart rate responses to increasing doses of isoprenaline (n = 6) (during infusion with atropine 0.5 mg/min i.v.) and noradrenaline (n = 5), (during infusion with phentolamine 160 mg/h i.v.) were recorded before and after the intravenous administration of propranolol (15 mg) or metoprolol (15 mg). 2 In the doses ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01911.x
更新日期:1982-01-01 00:00:00
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract::The excretion of diazepam, N-desmethyldiazepam, temazepam and oxazepam in breast milk was studied during withdrawal of a 22-year-old patient from combined high dose diazepam and oxazepam therapy. Concentrations of these benzodiazepines in plasma from both the woman and her nursing infant (1 year old) were also documen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03612.x
更新日期:1990-01-01 00:00:00
abstract::1. A novel formulation of nicardipine (50% standard (short acting), 50% sustained release) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled study, using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. Nicardipine 60 mg twice daily for 28 ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1989.tb03418.x
更新日期:1989-05-01 00:00:00
abstract::1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocyte 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of various groups of patients--those who have not received digoxin, those during the early phases of treatment, those...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb05811.x
更新日期:1979-08-01 00:00:00
abstract:AIMS:To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. METHODS:Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2009.03476.x
更新日期:2009-10-01 00:00:00
abstract:AIMS:Homeopathic medicines are frequently purchased over the counter (OTC). Respiratory complaints are the most frequent reason for such purchases. Children with upper respiratory tract infection (URTI) are frequent users of homeopathy. This study investigates the effect of self treatment with one of three self selecte...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2005.02336.x
更新日期:2005-04-01 00:00:00
abstract:AIM:In short-term studies, hormonal contraceptives (HC) have been suggested to induce a rise in blood pressure (BP) and urinary albumin excretion (UAE), while the effect of HC in renal function (GFR) is still under debate. Data on long-term and withdrawal effects of HC use on these outcomes are, however, not available....
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02747.x
更新日期:2007-02-01 00:00:00
abstract:AIMS:SAR247799 is a selective G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1 ) agonist with potential to restore endothelial function in vascular pathologies. SAR247799, a first-in-class molecule differentiated from previous S1P1 -desensitizing molecules developed for multiple sclerosis, can activate S1P1 wi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14422
更新日期:2020-06-10 00:00:00
abstract::1 We have given fifteen healthy volunteers single doses of racemic (+/-)-propranolol orally (40 mg) and intravenously (5-10 mg) to find out how large the variation was of the ratio between (-)- and (+)-propranolol plasma levels in relation to that of total levels of propranolol and 4-hydroxypropranolol. 2 Total propra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04937.x
更新日期:1982-07-01 00:00:00
abstract::1 In a preliminary double-blind trial the effects of ephedrine and pseudoephedrine on the blood pressure and heart rate of resting healthy volunteers were compared. Ephedrine 60 or 90 mg were required to raise the diastolic blood pressure above 90 mmHg, whereas 210 or 240 mg pseudoephedrine were required to produce th...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1978.tb04588.x
更新日期:1978-09-01 00:00:00
abstract:AIMS:To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of brotizolam. METHODS:Fourteen healthy male volunteers received erythromycin 1200 mg day(-1) or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2005.02380.x
更新日期:2005-08-01 00:00:00
abstract:AIMS:Changes in serotonergic sensory modulation associated with overexpression of 5-HT3 receptors in the central nervous system (CNS) have been implicated in the pathophysiology of neuropathic pain after peripheral nerve damage. 5-HT3 receptor antagonists such as ondansetron can potentially alleviate neuropathic pain, ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14412
更新日期:2020-06-04 00:00:00