Abstract:
BACKGROUND:Reduction in plasma low-density lipoprotein cholesterol (LDL-C) is a fundamental treatment for the prevention of acute coronary syndromes (ACS). Although statin therapy confers significant protection against ACS in both primary and secondary prevention, a considerable residual risk remains after intensive therapy. In addition, a significant proportion of high-risk patients do not achieve the optimal LDL-C goal recommended in the current guidelines (<1.8 mmol/L). Hence, novel LDL-C-lowering agents that act via mechanisms distinct from HMG-CoA reductase inhibition are under investigation. OBJECTIVE:We reviewed the recent literature on the development of novel LDL-C-lowering agents that could potentially be used as an alternative or adjunct to statin therapy in high-risk coronary patients. METHODS:PubMed and Scopus databases were searched to retrieve studies on the efficacy and/or tolerability of novel LDL-C-lowering agents in animals and humans. RESULTS:Agents that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein (apo) B, and microsomal triglyceride transfer protein (MTTP) are the most promising therapies. Inhibition of PCSK9, apoB, and MTTP has been achieved mostly via fully humanized monoclonal antibodies (mAbs), antisense oligonucleotides, and synthetic compounds, respectively. PCSK9 inhibitors increase the hepatic uptake of LDL-C, while apoB and MTTP inhibitors decrease the synthesis and secretion of apoB-containing lipoproteins. These 3 mechanisms lead to marked reductions in plasma LDL-C in patients with hypercholesterolemia at risk for ACS, particularly those with familial hypercholesterolemia. Moreover, these agents can exert additional benefits by decreasing plasma levels of apoB, triglycerides, and lipoprotein(a). Mipomersen and lomitapide have been approved by the United States Food and Drug Administration (US FDA) for use in patients with homozygous familial hypercholesterolemia. PCSK9 inhibitors are currently under final evaluation in clinical outcomes studies and are anticipated to find wide application either as monotherapy or as an adjunct to statins. A main safety concern is the risk for hepatic steatosis with apoB and MTTP inhibitors, which needs to be explored in prospective, long-term trials. CONCLUSIONS:PCSK9, apoB, and MTTP inhibitors can exert potent reductions in plasma LDL-C and apoB concentrations, either as monotherapy or in combination with statins. These effects are particularly relevant to high-risk individuals with marked hypercholesterolemia, such as those with familial hypercholesterolemia. Although the use of mipomersen and lomitapide is limited to severe familial hypercholesterolemia as a replacement for LDL-apheresis, PCSK9 inhibitors are likely to be more widely prescribed in patients at high risk for CVD, especially those who are resistant to or intolerant of high-intensity statin therapy. PCSK9 mAbs are efficacious and have an excellent safety profile, but their long-term impact on cardiovascular events is currently under investigation. Whether PCSK9 mAbs decrease the rates of recurrent cardiovascular events within 3 months following ACS is questionable; however, these agents, unlike statins, may not have pleiotropic benefits on the unstable plaque.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Sahebkar A,Watts GFdoi
10.1016/j.clinthera.2013.06.019subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1082-98issue
8eissn
0149-2918issn
1879-114Xpii
S0149-2918(13)00347-0journal_volume
35pub_type
杂志文章,评审abstract:BACKGROUND:Ezetimibe (EZE) is a cholesterol-lowering drug that inhibits absorption of dietary and biliary cholesterol across the intestinal wall without affecting absorption of bile acids, fatty acids, fat-soluble vitamins, or triglycerides. It has a complementary mechanism of action to the statins, which inhibit chole...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2005.02.011
更新日期:2005-02-01 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:BACKGROUND:In people with type 1 or type 2 diabetes, poor adherence to insulin therapy can compromise disease management. There are several reasons for poor adherence, including social embarrassment, inconvenience, needle anxiety, fear of injection pain, and complicated regimens. Attempts to facilitate implementation o...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2005.11.019
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers. M...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.09.022
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Insulin therapy may eventually be required to maintain glycemic control in many patients with type 2 diabetes mellitus. Premixed insulin analogues offer relatively physiologic and predictable time-action profiles and are available in more convenient delivery systems with finer needles than in the past. They ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2005.07.003
更新日期:2005-08-01 00:00:00
abstract::This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depre...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(97)80066-5
更新日期:1997-09-01 00:00:00
abstract:OBJECTIVES:This study evaluated adherence to anti-inflammatory controller medication for asthma in a French population. METHODS:This was an observational cohort study that employed data from the health insurance database for the Aquitaine region of France. Eligible subjects were aged between 15 and 45 years and had > ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.06.011
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Use of cholesterol-lowering regimens has been shown to reduce the risk of coronary heart disease (CHD), both in primary and secondary prevention. However, there have been few studies of the relative benefits and risks of the various cholesterol-lowering agents in patient groups with specific risk factors for...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(01)80050-3
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:The continuing increase in the rate of penicillin and cephalosporin resistance among respiratory pathogens and of cross-resistance to macrolide antibiotics has led to the recommendation that fluoroquinolone antibiotics be used to treat high-risk patients with community-acquired pneumonia (CAP) and acute bact...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(00)89007-4
更新日期:2000-04-01 00:00:00
abstract::Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheles...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The field of rheumatology has made major contributions to medicine through the identification of cellular and molecular targets and with the development of therapies for the treatment of an impressive range of immune-mediated rheumatic diseases. In recent years new milestones have been achieved. These include the reco...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.04.014
更新日期:2019-07-01 00:00:00
abstract:PURPOSE:Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. METHODS:Pati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.10.013
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:The International Conference on Harmonisation E14 guideline mandates an intensive cardiac safety evaluation in a clinical thorough QT study, typically in healthy subjects, for all new non-antiarrhythmic drugs with systemic bioavailability. This thorough QT study investigated the effects of therapeutic (2 mg) an...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.09.006
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Migraine is a common, chronic, often disabling neurologic condition that is underdiagnosed and undertreated. OBJECTIVE:We undertook this questionnaire-based study as a substudy of a multicenter trial of rizatriptan effectiveness. Our goal was to assess the history of acute migraine medication use and the re...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0149-2918(03)80204-7
更新日期:2003-07-01 00:00:00
abstract::This paper reviews the issues that are critical for the valuation of medical resources in the context of health economic studies. There are several points to consider when undertaking the valuation of medical resources. The perspective of the analysis should be established before determining the valuation process. Fut...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1994-05-01 00:00:00
abstract::The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these pati...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/j.clinthera.2008.01.015
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Heart failure places a burden on patients and health care systems worldwide. Although the advent of angiotensin-converting enzyme (ACE) inhibitors markedly improved management of this chronic disorder, treatment is still not optimal, and morbidity and mortality remain high. OBJECTIVE:This review summarizes ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/s0149-2918(01)80120-x
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data. OBJECTI...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(00)83032-5
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singap...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.05.009
更新日期:2014-07-01 00:00:00
abstract::Neisseria microorganisms (Neisseria lactamica, Neisseria sicca, and Neisseria mucosa) are regarded as normal respiratory commensals. Branhamella catarrhalis (formerly Neisseria catarrhalis) has also been regarded as a normal respiratory commensal, but reports indicate that it can be pathogenic. The role of Neisseria s...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Twenty-four patients with pulmonary infections (7 pneumoniae, 17 exacerbations of chronic bronchitis) were treated with a combination of 250 mg of amoxicillin and 125 mg of clavulanic acid supplemented by 500 mg of amoxicillin every eight hours. All patients showed good clinical, roentgenological, and bacteriological ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND:The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. OBJEC...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.09.010
更新日期:2011-11-01 00:00:00
abstract::The efficacy and safety of transferring 76 patients with poorly controlled type II diabetes mellitus from various self-mixed human insulin regimens to a premixed insulin regimen (Novolin 70/30, 70% NPH and 30% Regular insulin, semisynthetic) were evaluated in a 24-week, multicenter, open-label study. During the initia...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Geriatric patients are more sensitive to the anesthetic effects of propofol and its adverse effects, such as hypotension, than is the general population; thus, a reduced dose (1-1.5 mg/kg) is recommended for the induction of anesthesia. The extent to which clinicians follow established dosing guidelines has not...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.10.005
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:Few studies have determined the benefits of pharmacist-run clinics within a tertiary institution, and specifically on their capability to improve clinical outcomes as well as reduce the cost of illness. This study was designed to investigate the effectiveness of a pharmacist-managed risk factor management clini...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.10.009
更新日期:2017-12-01 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::The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid-acting insulin with a shorter duration of activity than human regular insulin. This compound has the advantage of reducing early postprandial hyperglycemia and the accompanying late hypoglycemia, thereby improving overall blood glucose control...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80040-4
更新日期:1998-01-01 00:00:00
abstract::The causes of past accidental viral transmissions associated with blood derivatives are reviewed briefly, as are the safety procedures instituted in Europe on the basis of viral validation studies. A comprehensive five-class classification system for delineating viral risk according to source material and comparative ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(96)80194-9
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:The prevalence of asthma is increasing, and this chronic condition imposes a substantial economic burden worldwide. It is not known whether newer therapies, such as leukotriene receptor antagonists (LTRAs), can ease this burden. OBJECTIVE:This analysis examined the association between choice of first-line a...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(01)80130-2
更新日期:2001-09-01 00:00:00