Ezetimibe for Management of Hypercholesterolemia

2003 ◽  
Vol 37 (6) ◽  
pp. 839-848 ◽  
Author(s):  
Vincent F Mauro ◽  
Chad E Tuckerman
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Outcome Data ◽  
Lipoprotein Cholesterol ◽  
Intestinal Cell ◽  
Medline Search ◽  
Concurrent Use

OBJECTIVE: To review the primary literature describing the pharmacology of ezetimibe and clinical trials investigating its use in the management of hypercholesterolemia. DATA SOURCES: A MEDLINE search (1966–December 2002) was performed using SCH 48461, SCH 58235, ezetimibe, and 2-azetidinone as key words. English-language articles were identified and the references of these articles were used to further identify pertinent articles and abstracts. Given the paucity of published articles available on ezetimibe, many of the references cited are abstracts. STUDY SELECTION: All acquired articles that discussed the pharmacology, pharmacokinetics, chemistry, and clinical efficacy of ezetimibe were reviewed. DATA EXTRACTION: Articles were selected based on content regarding the medicinal chemistry, pharmacology, and clinical use of ezetimibe. DATA SYNTHESIS: Ezetimibe, approved for use in October 2002, belongs to a new class of antihyperlipidemic agents that uniquely inhibit the absorption of cholesterol by inhibiting the cholesterol transport system located within intestinal cell walls. In humans, ezetimibe reduced cholesterol absorption by >50%. In clinical trials, ezetimibe 10 mg/d reduced low-density lipoprotein cholesterol (LDL-C) by approximately 18% and further enhanced the LDL-C–lowering effect of statin medications by an additional 15–20%. In addition, ezetimibe lowered triglycerides about 5% and increased high-density lipoprotein cholesterol (HDL-C) approximately 3%. Ezetimibe is well tolerated. At present, no serious adverse effects have been directly attributable to ezetimibe. CONCLUSIONS: Based on the data currently available, it appears that ezetimibe has a potential role in the treatment of primary hypercholesterolemia; however further data are needed to determine its long-term tolerability and efficacy. The potential roles for ezetimibe include its concurrent use with a statin to further enhance the lowering of LDL-C. Other possible roles for ezetimibe include its concurrent use with a statin to permit a lowering of statin dosage to avoid statin-related complications or its use as monotherapy to treat hypercholesterolemia when statin use cannot be tolerated or is contraindicated. Outcome data demonstrating that cardiovascular morbidity and/or mortality are reduced by ezetimibe therapy have yet to be generated.

Leukotriene-Receptor Antagonists and 5-Lipoxygenase Inhibitors in Asthma

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Background Information ◽  
Receptor Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Medline Search ◽  
Leukotriene Receptor Antagonists ◽  
Patient Tolerance ◽  
Leukotriene Receptor

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.

Levoleucovorin as Replacement for Leucovorin in Cancer Treatment

2012 ◽  
Vol 46 (10) ◽  
pp. 1349-1357 ◽  
Author(s):  
Victor Tuan Giam Chuang ◽  
Manabu Suno
Keyword(s):  
Clinical Trials ◽  
Cancer Treatment ◽  
Clinical Studies ◽  
English Language ◽  
Antitumor Agents ◽  
Data Extraction ◽  
Phase 1 ◽  
Phase 3 ◽  
Medline Search ◽  
Reasonable Alternative

Objective: To comprehensively review the literature regarding the efficacy, safety, and costs associated with the use of levoleucovorin in cancer treatment and to assess whether levoleucovorin would be a reasonable alternative to the use of racemic leucovorin. Data Sources: A MEDLINE search was conducted for English-language human studies published between January 1980 and April 2012 using the terms I-LV. levoleucovorin, d,I-LV, leucovorin, folinic acid, tolinate, 5-formyltetrahydrofolate, folic acid, folates, methotrexate, 5-fluorouracil, and clinical trials. Study Selection and Data Extraction: Articles pertinent to clinical trials (Phase 1, 2, 3) related to evaluating the efficacy, interchangeability, and safety of levoleucovorin were collected and their contents reviewed. Data Synthesis: From these pharmacokinetics and clinical studies, information on the use of levoleucovorin as a modulator of fluorouracil as well as when combined with other antitumor agents were scrutinized and extracted for comparison with leucovorin whenever possible. Two randomized Phase 3 clinical studies comparing the efficacy and adverse effect profiles of leucovorin and levoleucovorin demonstrated that levoleucovorin is as effective as leucovorin in terms of response, toxicity, and survival. Six randomized Phase 3 clinical studies demonstrated the safety and efficacy of levoleucovorin as a modulator of fluorouracil in combination with/without other antitumor agents in colorectal cancer patients. Levoleucovorin has been studied in other cancers. These clinical Phase 1/2/3 studies demonstrated efficacy and safety of levoleucovorin in combination chemotherapeutic regimens comprising fluorouracil and other antitumor agents. Conclusions: The results of the clinical studies suggest that levoleucovorin is efficacious and can be used safely in combination with fluorouracil and other antitumor agents. Levoleucovorin can be used interchangeably with leucovorin for modulating fluorouracil. The current shortage of the supply of leucovorin centered in North America renders levoleucovorin a reasonable alternative in terms of efficacy and toxicity profile, but from the perspective of cost, leucovorin remains the drug of choice.

Zolpidem: Distinct from Triazolam?

1997 ◽  
Vol 31 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Bob L Lobo ◽  
William L Greene
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Memory Impairment ◽  
English Language ◽  
Data Extraction ◽  
Residual Effects ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Pertinent Information

OBJECTIVE: TO review the literature that compares Zolpidem with triazolam, with an emphasis on efficacy and safety in humans. DATA SOURCES: Information was retrieved from a MEDLINE search (1983–1996) of the English-language literature using the terms triazolam and zolpidem. STUDY SELECTION: Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review. DATA EXTRACTION: Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects. CONCLUSIONS: Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.

Role of Acetyl-L-Carnitine in the Treatment of Diabetic Peripheral Neuropathy

2008 ◽  
Vol 42 (11) ◽  
pp. 1686-1691 ◽  
Author(s):  
Jeffery D Evans ◽  
Tibb F Jacobs ◽  
Emily W Evans
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
English Language ◽  
Data Extraction ◽  
Disease Process ◽  
Medline Search ◽  
Treatment And Prevention ◽  
Meta Analyses

Objective: To examine the role of acetyl-L-carnitine (ALC) in the treatment of diabetic peripheral neuropathy (DPN). Data Sources: A MEDLINE search (1966–April 2008) of the English-language literature was performed using the search terms carnitine, diabetes, nerve, and neuropathy. Studies identified were then cross-referenced for their citations. Study Selection and Data Extraction: The search was limited to clinical trials, meta-analyses, and reviews addressing the use of ALC for the treatment of DPN. Studies that included other disease states that could cause peripheral neuropathy were excluded. Two large clinical studies that used ALC for the treatment of DPN were identified. No case studies were identified. Data Synthesis: The results from 2 published clinical trials Involving 1679 subjects were included. Subjects who received at least 2 g daily of ALC showed decreases in pain scores. One study showed improvements in electrophysiologic factors such as nerve conduction velocities, while the other did not. Patients who had neuropathic pain reported reductions in pain using a visual analog scale. Nerve regeneration was documented in one trial. The supplement was well tolerated, A proprietary form of ALC was used in both studies. Conclusions: Data on treatment of DPN with ALC support its use. It should be recommended to patients early in the disease process to provide maximal benefit. Further studies should be conducted to determine the effectiveness of ALC in the treatment and prevention of the worsening symptoms of DPN.

Acute Management of Cancer-Related Hypercalcemia

1996 ◽  
Vol 30 (5) ◽  
pp. 507-513 ◽  
Author(s):  
Marie A Chisholm ◽  
Anthony L Mulloy ◽  
A Thomas Taylor
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Symptomatic Relief ◽  
Gallium Nitrate ◽  
Medline Search ◽  
Patients With Cancer ◽  
Study Selection ◽  
Life Threatening ◽  
Acute Hypercalcemia

OBJECTIVE: TO review the pathogenesis and pharmacologic treatment of acute hypercalcemia associated with malignancy. DATA SOURCES: A MEDLINE search (1966 to 1995) of the English-language literature pertaining to acute hypercalcemia was performed. Additional literature was obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles discussing the etiology and medical management of cancer-related acute hypercalcemia were considered in the review. Clinical trials reporting efficacy and safety of antihypercalcemic agents were also included. Information selected in the review was based on the discretion of the authors. DATA SYNTHESIS: Hypercalcemia is a life-threatening disorder associated with malignancy. It occurs in approximately 10–20% of patients with cancer. A variety of medications have been used in the management of hypercalcemia including bisphosphonates, calcitonin, furosemide, gallium nitrate, glucocorticoids, NaCl 0.9%, and plicamycin. Each of these agents has been reviewed with consideration of pharmacologic mechanism of action, evaluation of clinical trials, recommended dosages, efficacy, safety, cost, and role in treating cancer-related acute hypercalcemia. CONCLUSIONS: Immediate management of cancer-related acute hypercalcemia to prevent death and provide symptomatic relief is warranted. Severity determined by symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Although the specific role of individual agents may vary, hydration remains the cornerstone of therapy. NaCl 0.9%, calcitonin, and Pamidronate disodium have established roles as dominant first-line agents for the management of acute hypercalcemia associated with malignancy.

Lipid Management with Statins in Type 2 Diabetes Mellitus

2005 ◽  
Vol 39 (10) ◽  
pp. 1714-1719 ◽  
Author(s):  
Brian K Irons ◽  
Lisa A Kroon
Keyword(s):  
Cardiovascular Disease ◽  
Relative Risk ◽  
Risk Reduction ◽  
Relative Risk Reduction ◽  
Data Extraction ◽  
Density Lipoprotein ◽  
Coronary Event ◽  
Lipid Management ◽  
Medline Search ◽  
Patients With Diabetes

OBJECTIVE: To provide an update on lipid management and recent modifications in cholesterol guidelines for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), specifically in patients with diabetes. DATA SOURCES: Studies and guidelines were identified through a MEDLINE search (1996–April 2005). STUDY SELECTION AND DATA EXTRACTION: Studies were selected for review if the primary treatment intervention was a statin, at least 4% of the study population held a diagnosis of diabetes, and diabetes subgroup analysis was available. DATA SYNTHESIS: The Heart Protection Study demonstrated an approximately 25% relative risk reduction of a first coronary event in patients with diabetes, a reduction similar to those without diabetes. In subjects with diabetes, a significant reduction in coronary events was noted regardless of the baseline cholesterol level. The Collaborative Atorvastatin Diabetes Study demonstrated a 37% relative risk reduction in the primary prevention of cardiovascular morbidity in patients with diabetes. CONCLUSIONS: Based on the current literature, a low-density lipoprotein cholesterol (LDL-C) level <100 mg/dL remains an appropriate goal for patients with diabetes in the absence of established cardiovascular disease. For higher-risk patients, such as those with diabetes and a history of cardiovascular disease, a more stringent LDL-C goal of <70 mg/dL is an option according to current clinical trial evidence. At least a 30–40% reduction in the LDL-C level is advisable when initiating statin therapy.

Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

2000 ◽  
Vol 34 (6) ◽  
pp. 743-760 ◽  
Author(s):  
Brigitte T Luong ◽  
Barbara S Chong ◽  
Dionne M Lowder
Keyword(s):  
Rheumatoid Arthritis ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

Ticlopidine and Antiplatelet Therapy

1993 ◽  
Vol 27 (9) ◽  
pp. 1090-1098 ◽  
Author(s):  
Patricia Flores-Runk ◽  
Ralph H. Raasch
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Artery Bypass ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Graft Patency ◽  
Diabetic Microangiopathy ◽  
Severe Reaction ◽  
English Language Journal

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of ticlopidine. Comparisons with other antiplatelet agents are presented, with an emphasis on efficacy, and a recommendation is provided regarding ticlopidine's place in therapy. DATA SOURCES: A MEDLINE literature retrieval of English-language journal articles from 1987 to January 1993 and references identified from bibliographies of review articles and clinical trials. STUDY SELECTION: Randomized, blind, controlled studies of ticlopidine and other antiplatelet agents were preferentially selected. DATA EXTRACTION: Clinical trials were reviewed in terms of study design, efficacy results, and toxicity. DATA SYNTHESIS: Ticlopidine is a new antiplatelet agent with a distinct mechanism of action. In the largest trial of the drug for the prevention of stroke, it was found to be more effective than aspirin in reducing the risk of stroke or death. Clinical trials have also shown ticlopidine to decrease the rate of vascular death and myocardial infarction in patients with unstable angina, and to maintain venous graft patency after coronary artery bypass grafting. The use of ticlopidine in diabetic microangiopathy and peripheral vascular disease appears promising, but further studies are needed. Adverse reactions most commonly reported with ticlopidine are gastrointestinal complaints; the most severe reaction is transient neutropenia, which is seen in approximately 2.3 percent of patients and is severe in nearly 1 percent. CONCLUSIONS: Ticlopidine is a reasonable alternative for use in preventing stroke among patients unable to take aspirin or those who do not benefit from aspirin therapy. Its use as first-line therapy is limited by its high cost and the occurrence of hematologic adverse effects.

scholarly journals Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Kun Zhang ◽  
Shan-Shan Dong ◽  
Yan Guo ◽  
Shi-Hao Tang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Blood Lipids ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Outcome Data ◽  
Causal Effects ◽  
Lipoprotein Cholesterol ◽  
Global Pandemic ◽  
The Uk

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2. It has been reported that dyslipidemia is correlated with COVID-19, and blood lipids levels, including total cholesterol, HDL-C (high-density lipoprotein cholesterol), and LDL-C (low-density lipoprotein cholesterol) levels, were significantly associated with disease severity. However, the causalities of blood lipids on COVID-19 are not clear. Approach and Results: We performed 2-sample Mendelian randomization (MR) analyses to explore the causal effects of blood lipids on COVID-19 susceptibility and severity. Using the outcome data from the UK Biobank (1221 cases and 4117 controls), we observed potential positive causal effects of dyslipidemia (odds ratio [OR], 1.27 [95% CI, 1.08–1.49], P =3.18×10 −3 ), total cholesterol (OR, 1.19 [95% CI, 1.07–1.32], P =8.54×10 −4 ), and ApoB (apolipoprotein B; OR, 1.18 [95% CI, 1.07–1.29], P =1.01×10 −3 ) on COVID-19 susceptibility after Bonferroni correction. In addition, the effects of total cholesterol (OR, 1.01 [95% CI, 1.00–1.02], P =2.29×10 −2 ) and ApoB (OR, 1.01 [95% CI, 1.00–1.02], P =2.22×10 −2 ) on COVID-19 susceptibility were also identified using outcome data from the host genetics initiative (14 134 cases and 1 284 876 controls). Conclusions: In conclusion, we found that higher total cholesterol and ApoB levels might increase the risk of COVID-19 infection.

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