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Biomedical subjects

Peter P Toth

Publications and source records attributed to Peter P Toth.

At least 19 recordsLinked to original sources
PubMed2007

Reducing cardiovascular risk by targeting high-density lipoprotein cholesterol.

Although lowering low-density lipoprotein (LDL) cholesterol with statins can substantially reduce cardiovascular morbidity and mortality, many treated patients retain a residual risk for cardiovascular events. Low levels of high-density lipoprotein (HDL) cholesterol may underpin this residual risk and may represent an additional target for intervention. Several new therapies for substantially increasing HDL cholesterol levels are under investigation, including cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I mimetics and recombinant HDL, liver X receptor (LXR) agonists, and peroxisome proliferator-activated receptor (PPAR) agonists. Combining new HDL cholesterol-elevating agents with existing LDL cholesterol-lowering agents may improve the cardiovascular risk reductions currently attainable.

Cardiovascular Diseases↗
PubMed2006

The CARDS trial: diabetic patients dealt a winning hand.

Until recently, the role of statin therapy in diabetic patients without clinical signs or symptoms of coronary heart disease had been inadequately defined. The Collaborative Atorvastatin Diabetes Study (CARDS) is a prospective, randomized, placebo-controlled trial designed to compare the effects of atorvastatin with placebo in preventing primary coronary events in diabetic patients. After a median of only 3.9 years (the study was terminated approximately 2 years early due to the magnitude of benefit attributable to atorvastatin therapy), risk for major cardiovascular events was decreased by 37%, acute coronary heart disease-related events were also reduced by 36%, coronary revascularizations by 31%, and stroke by 48%. Benefit emerged within 1 year of initiating therapy.

Atorvastatin↗
PubMed2006

Gender differences in adhering to national guidelines in a community lipid clinic.

The aggressive treatment of hypercholesterolemia improves morbidity and mortality in patients with a history of cardiovascular disease irrespective of gender. Electronically tracked data on 4324 patients enrolled in a community lipid clinic were analyzed for gender differences in lipid values and adherence to national guidelines in lipid management. Women were older, more likely to be diabetic and/or hypertensive, and have a family history of coronary heart disease. Women also had higher initial total cholesterol, low-density lipoprotein, and triglyceride levels and were more likely to be at goal at entry for high-density lipoprotein. Men were more likely to have coronary heart disease and lower high-density lipoprotein and were more likely to be at goal at entry for triglyceride level. There were no gender differences in low-density lipoprotein at goal at entry or rate of current smoking. All lipid parameters appeared better with age, irrespective of gender. More men than women reached goal for their low-density lipoprotein (61.5% vs 51.7%) and triglyceride (36.9% vs 25.1%) levels, whereas more women than men reached goal for their high-density lipoprotein (33.1% vs 22.2%). The authors conclude that there are significant gender differences in lipid values at entry to a community lipid clinic and in achieving National Cholesterol Education Program targets following the initiation of therapy. A possible gender-independent survivorship effect exists for low-density lipoprotein and high-density lipoprotein.

Aged↗
PubMed2006

Colesevelam hydrochloride in the management of dyslipidemia.

Dyslipidemia is a highly heterogeneous group of disorders strongly influenced by both genetic and environmental factors. Dyslipidemia significantly increases risk for atherosclerotic disease and all of its various clinical manifestations. Identifying patients with dyslipidemia and initiating therapies aimed at normalizing the lipid profile has been demonstrated to significantly reduce the risk for myocardial infarction, stroke and cardiovascular mortality in both the primary and secondary prevention settings. Guidelines in Europe, Canada and the USA emphasize the need to reduce the burden of atherogenic lipoproteins in serum and to raise levels of high-density lipoproteins in patients at risk for cardiovascular events. Statins have emerged as front-line therapy for managing dyslipidemia, especially in patients with elevated serum levels of low-density lipoprotein cholesterol. As guidelines emphasize the need to reduce serum low-density lipoprotein cholesterol to lower levels, goal attainment can be challenging. The use of combination therapy increases the likelihood of therapeutic success for many patients. Furthermore, a significant percentage of patients with dyslipidemia either cannot achieve goals on statin monotherapy, choose not to take a statin or do not tolerate these drugs due to adverse side effects, such as myalgias, weakness or hepatotoxicity. This article summarizes the pharmacology, clinical efficacy and safety of colesevelam hydrochloride, a bile acid-binding resin. Bile acid-binding resins are orally administered anion-exchange resins that are not absorbed systemically. These agents bind bile acids and reduce their reabsorption at the level of the terminal ileum and prevent their enterohepatic recirculation. Colesevelam has a favorable side effect and toxicity profile and significantly impacts serum levels of lipoproteins when used as monotherapy or when used in combination with either statins or ezetimibe.

Allylamine↗
PubMed2005

High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies.

The clinical importance of low serum levels of high-density lipoprotein (HDL) cholesterol is often under-recognized and underappreciated as a risk factor for premature atherosclerosis as well as for cardiovascular morbidity and mortality. Low serum levels of HDL are frequently encountered, especially in patients who are obese or have the metabolic syndrome. In prospective epidemiologic studies, every 1-mg/dL increase in HDL is associated with a 2% to 3% decrease in coronary artery disease risk, independent of low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. The primary mechanism for this protective effect is believed to be reverse cholesterol transport, but several other anti-inflammatory, antithrombotic, and antiproliferative functions for HDL have also been identified. In recognition of these antiatherogenic effects, recent guidelines have increased the threshold for defining low levels of HDL for both men and women. The first step in achieving these revised targets is therapeutic lifestyle changes. When these measures are inadequate, pharmacotherapy specific to the patient's lipid profile should be instituted. Niacin therapy, currently the most effective means for raising HDL levels, should be initiated in patients with isolated low HDL (HDL <40 mg/dL, LDL and non-HDL at or below National Cholesterol Education Program (NCEP) targets based on global cardiovascular risk evaluation). Patients who have both low HDL and elevated LDL should receive a statin or statin-niacin combination therapy, and patients with concomitant low HDL and elevated TGs should receive a fibrate initially, with a statin, niacin, or ezetimibe added thereafter as needed to help attain NCEP lipoprotein targets.

Atherosclerosis↗
PubMed2005

New insights in the treatment of dyslipidemia: a focus on cardiovascular event reduction and the anti-atherosclerotic effects of atorvastatin.

The identification and treatment of dyslipidemia is a critical component of ongoing efforts to reduce the incidence of atherosclerotic disease in both men and women. Several recent large-scale atorvastatin trials provide a plethora of information that expands the current body of literature describing the pathophysiology of cardiovascular disease and the prevention of acute cardiovascular events. These trials demonstrate the benefit of statin therapy in a broad variety of patient populations, explore the clinical efficacy of more intensive statin regimens, and suggest that the pleiotropic effects of statins may contribute to cardiovascular endpoint reduction. In addition, these studies have challenged whether current guidelines for low-density lipoprotein cholesterol levels provide optimal risk reduction for cardiovascular events. Additional studies with atorvastatin are underway to further explore the extent to which statins can provide cardiovascular benefits.

Anticholesteremic Agents↗
PubMed2005

Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia.

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease. A part of the reluctance to treat different lipoprotein fractions to goal levels is attributable to physician- and patient-related concerns over the increasing toxicity of available therapies, as their dosages are increased. The risks of hepatotoxicity, myalgia, and rhabdomyolysis are fairly well characterised in patients receiving statins, fibrates and niacin. Another issue affecting treatment success rates is the fact that many patients with complex dyslipidaemias are inadequately responsive to single-agent therapy. As the epidemics of obesity, metabolic syndrome and diabetes mellitus continue to worsen, physicians will encounter severe, mixed dyslipidaemias more frequently. Many of these patients will require combinations of drugs to address the various metabolic derangements causing changes in multiple lipoprotein fractions. Although the need for combination therapy is well-established in the management of disorders, such as hypertension and diabetes, it is less often used for the treatment of dyslipidaemias. The development of safe, cost-effective, and efficacious combination dyslipidaemic therapy is an important goal in cardiovascular medicine. Simvastatin plus ezetimibe has recently been combined as a fixed dose therapy, which offers clinicians the opportunity to simultaneously inhibit two key pathways in cholesterol metabolism: hepatic cholesterol biosynthesis and the absorption of cholesterol at the level of the proximal jejunum. This dual mechanism of inhibition substantially increases the capacity to decrease serum levels of atherogenic low-density lipoproteins and increase high-density lipoprotein, compared with that observed when either drug is used alone. This combination increases the likelihood of therapeutic success in patients with dyslipidaemia.

Azetidines↗
PubMed2005

Cholesterol absorption blockade with ezetimibe.

The reduction of circulating atherogenic lipoproteins through lifestyle modification and pharmacologic intervention is an important therapeutic goal in patients at risk for acute cardiovascular events. A large number of clinical trials have demonstrated that the reduction of low-density lipoprotein cholesterol (LDL-C) is associated with significant decreases in the incidence of all cause mortality, stroke, fatal and nonfatal myocardial infarction, and the need for revascularization with coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (i.e., statins) are the agents of choice for treating a variety of dyslipidemias, particularly when LDL-C levels are elevated. The statins are highly efficacious; however, not all patients are able to tolerate the higher doses of these medications due to adverse side-effects such as hepatoxicity and myotoxicity. Moreover, many patients cannot achieve their various lipoprotein targets at even the highest doses of these medications. Ezetimibe is a novel cholesterol absorption inhibitor that blocks the translocation of dietary and biliary cholesterol from the gastrointestinal lumen into the intracellular space of jejunal enterocytes. Ezetimibe undergoes enterohepatic recirculation with minimal systemic exposure and not does not adversely impact the pharmacokinetic profile of statins. Ezetimibe significantly reduces serum LDL-C. It is safe when used as monotherapy or when used in combination with statins. Ezetimibe is indicated in the management of hyperlipidemia, familial hypercholesterolemia, and sitosterolemia and significantly increases the percentage of patients able to reach their lipid-lowering goals.

Anticholesteremic Agents↗
PubMed2004

Low-density lipoprotein reduction in high-risk patients: how low do you go?

Cardiovascular disease and its clinical sequelae remain the leading causes of morbidity and mortality in many regions of the world. Dyslipidemia is a critical risk factor to intercept in both the primary and secondary prevention of acute cardiovascular events. The prospective, placebo-controlled clinical trials conducted with statins over the course of the past 15 years have conclusively demonstrated that these drugs significantly reduce risk for fatal and nonfatal myocardial infarction, ischemic stroke, unstable angina, and frequency of myocardial ischemia, as well as cardiovascular and all-cause mortality. Of considerable interest is the fact that, even under the exquisitely controlled circumstances of a clinical trial, endpoint reductions in these trials typically occur in the range of 20% to 35%. Understandably, much attention is now being focused on deriving the pharmacologic means by which to further increase the magnitude of endpoint reduction. Epidemiologic investigation has demonstrated that the relationship between cholesterol and risk for atherosclerotic disease is a continuous one. Consequently, it is reasonable to assume that more aggressive reductions of low-density lipoprotein (LDL) cholesterol might result in even greater reductions of cardiovascular event rates and atheromatous plaque progression than heretofore observed. Two recent clinical trials, Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT), prospectively tested and confirmed the validity of more aggressive LDL cholesterol lowering in high-risk patients with established coronary artery disease.

Cardiovascular Diseases↗
PubMed2004

Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone.

BACKGROUND: Low back pain is a leading reason for primary care visits. Many treatment options are available, but some lack scientific support. OBJECTIVE: The aim of this review was to discuss the etiology of low back pain and the relative risks and benefits of muscle relaxants commonly prescribed for the management of back pain. METHODS: We searched Intercontinental Marketing Services data for January 2003 through January 2004 to determine the most commonly prescribed agents for the management of musculoskeletal pain. Carisoprodol, cyclobenzaprine hydrochloride, and metaxalone represented >45% of all such prescriptions. Cochrane Library, MEDLINE, and EMBASE databases were searched (time frame: 1960 through January 2004; search terms: back pain, carisoprodol, cyclobenzaprine, metaxalone, muscle relaxants, and pharmacotherapy) and reference lists of identified articles were hand-searched. RESULTS: Three trials of carisoprodol (N = 197) were located in the Cochrane Library database. Two double-blind, randomized, placebo-controlled trials evaluating the safety and efficacy of cyclobenzaprine hydrochloride (N = 1405) were identified in the literature. Three double-blind, placebo-controlled trials were identified for metaxalone (N = 428) in 2 reports. The types of adverse events seen with these agents involved the central nervous system, including drowsiness/sedation, fatigue, and dizziness. However, the efficacy of cyclobenzaprine hydrochloride was shown to be independent of its sedative effects, which were dose related. The potential for abuse with carisoprodol is of growing concern. CONCLUSIONS: Analgesic pain management for low back pain due to muscle spasm may be combined with a muscle relaxant. Cyclobenzaprine hydrochloride has the most recent and largest clinical trials demonstrating its benefit, but carisoprodol and metaxalone also appear to be effective. However, carisoprodol's usefulness is mitigated by its potential for abuse.

Amitriptyline↗
PubMed2004

Therapeutic interventions targeted at the augmentation of reverse cholesterol transport.

PURPOSE OF REVIEW: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT. RECENT FINDINGS: Low levels of HDL are commonly encountered in patients with atherosclerotic disease. HDLs mediate a substantial number of antiatherogenic effects along blood vessel walls. One of the most important of these antiatherogenic mechanisms is RCT, a series of reactions by which HDL is able to facilitate the net translocation of cholesterol from peripheral cells to the liver for excretion. There is scientific evidence supporting the concept of RCT in both animals and humans. To facilitate RCT, it is important that therapeutic effort be made to raise serum levels of HDL. Statins, fibrates, niacin, thiazolidinediones, and various combinations of these drugs all raise HDL levels. However, in many high-risk patients with established atherosclerotic disease, the elevations in HDL achieved with these medications are frequently inadequate. Newer agents designed to raise HDL and promote RCT are currently being developed, including infusible bioengineered HDL, edible HDL composed of D-amino acids, and agents capable of inhibiting cholesterol ester transfer protein, among others. SUMMARY: Established therapies for raising HDL can be effective either as monotherapy or when used in combination. Newer strategies are being developed to exploit more specifically the capacity of HDL to drive RCT and either prevent or reverse the course of atherosclerotic disease.

Apolipoprotein A-I↗
PubMed2004

Combination therapy in the management of complex dyslipidemias.

PURPOSE OF REVIEW: Patients with dyslipidemias continue to be undertreated in both the primary and secondary prevention settings. Many patients have therapeutic needs that exceed simple reductions in low-density lipoprotein levels using statins. This review discusses the need for comprehensive management of all abnormalities in a given patient's lipoprotein profile and for the use of combinations of anti-lipidemic medications, when indicated. RECENT FINDINGS: The majority of high-risk patients with manifestations of atherosclerotic disease or who have a coronary artery disease risk equivalent are not meeting their various lipoprotein targets. There is considerable reluctance to titrate statins and to use combinations of anti-lipidemic medications in patients not reaching their various lipoprotein targets. Combinations of anti-lipidemic medications can be specifically tailored to address abnormalities in multiple lipoprotein fractions. Recent clinical trials clearly demonstrate that combination therapy is well tolerated and facilitates lipoprotein goal attainment. SUMMARY: Therapeutic approaches that incorporate the use of multiple anti-lipidemic medications should be more widely adopted in order to increase the number of patients able to meet their lipoprotein goals and to produce more substantially reduced risks for acute cardiovascular events.

Algorithms↗