High Good Cholesterol More Important Than Low Bad Cholesterol For Heart Protection

Having a high level of HDL cholesterol - the good cholesterol - is more important than having a low level of LDL - the bad cholesterol - in protecting individuals from heart attack, according to a study published in the March issue of American Heart Journal by researchers from the Indiana University School of Medicine and pharmaceutical company GlaxoSmithKline, Inc.


The researchers looked at the history of heart disease, age, sex, race, weight and other heart disease risk factors in almost 7,000 patients. The patients were predominately inner city residents and included a large number of African Americans, women, smokers and overweight people. The researchers found the strongest predictor of future heart attack was previous heart disease; age was the second strongest predictor and the third strongest predictor was HDL level.


"Most of the drugs that lower LDL also tend to raise HDL so until our study, when a person's health improved, you couldn't tell if that was due to lowering of the LDL or raising the HDL level," says study senior author William Tierney, M.D., IU Chancellor's Professor of Medicine and a Regenstrief Institute Inc. research scientist. "We now know that more good cholesterol is more important than less bad cholesterol.


"Having a high total cholesterol reading may not be bad, in fact it may be good if it's the HDL component which is high. Conversely, a low total cholesterol reading, is not necessarily good because it can hide a low HDL level," said Dr. Tierney.


This study was repeated with stroke as the outcome rather than heart disease, and the same results were the same: HDL cholesterol was a strong predictor of stroke, and the LDL cholesterol was not.


Current guidelines for treating cholesterol focus only on LDL cholesterol. That's not enough: they should focus on both HDL and LDL, according to Dr. Tierney. He calls for guidelines to be revised to encourage physicians and their patients to pay closer attention to HDL cholesterol.


Co-authors of the study are Timothy Stump, M.S. of the Regenstrief Institute, Inc. and Carol E. Koro, Ph.D.; Steven Bowlin, D.O., Ph.D.; and Dennis L. Sprecher, M.D. of GlaxoSmithKline, Inc. GlaxoSmithKline, Inc. funded the research.


medicine.iu

Cholesterol Precursors Can Cause Developmental Defects

Although high levels of cholesterol are bad for us (putting us at increased risk of a heart attack), low levels of cholesterol can also be bad -- as a fetus, low levels of cholesterol are associated with life-long disabilities, such as learning difficulties, limb abnormalities, and cleft palate. Low levels of cholesterol during development are caused by genetic defects in the proteins that control the production of cholesterol. Therefore, these individuals not only have low levels of cholesterol but also high levels of cholesterol precursors; which of these cause the developmental defects has been a matter of debate. Now, researchers from the University of Texas Southwestern Medical Center have shown that in mice it is the high levels of cholesterol precursors that are to blame.



In their study, which appears in the September issue of the Journal of Clinical Investigation, Joseph Goldstein and colleagues found that fetal mice with normal levels of cholesterol but very high levels of cholesterol precursors had severe developmental defects, including cleft palate. Treating female mice during pregnancy with a statin (a drug that decreases the production of cholesterol) reduced the level of cholesterol precursors in the fetal mice and decreased the incidence of cleft palate. This study provides enormous insight into why certain gene defects cause disability.



In an accompanying commentary, Forbes Porter from the National Institutes of Health puts this work in context with other recent advances and outlines the work that remains before we can fully understand how high levels of cholesterol precursors cause disabilities.



TITLE: Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovaststin



AUTHOR CONTACT:



Joseph L. Goldstein


University of Texas Southwestern Medical Center, Dallas, Texas, USA.


E-mail: joe.goldsteinutsouthwestern.



Michael S. Brown


University of Texas Southwestern Medical Center, Dallas, Texas, USA.


E-mail: mike.brownutsouthwestern.



View the PDF of this article at: https://the-jci/article.php?id=28988



ACCOMPANYING COMMENTARY



TITLE: Cholesterol precursors and facial clefting



AUTHOR CONTACT:



Forbes D. Porter


National Institutes of Health, Bethesda, Maryland, USA.


E-mail: fdportermail.nih.



View the PDF of this article at: https://the-jci/article.php?id=29872







JCI table of contents: September 1, 2006



Contact: Karen Honey

Journal of Clinical Investigation

Study Finds Statins Do Not Interfere With Rituximab Treatment For Lymphomas

Statins, drugs widely prescribed to lower cholesterol, do not interfere with a commonly used medication to treat lymphomas, according to a Mayo Clinic study presented at the 50th Annual Meeting of the American Society of Hematology (hematology/meetings/2008/) in San Francisco. In fact, statins may slow the progression of certain types of lymphoma.



The study focused on the impact of statin use on outcomes of patients with two most common lymphoma types, diffuse large B-cell lymphoma and follicular lymphoma. Both are cancers of the immune system. Examples of commonly used statins in the U.S. include Lipitor, Zocor, Parvachol, Lescol, Mevacor and Crestor.



Rituximab (Rituxan), a monoclonal antibody, is often used alone or in conjunction with chemotherapy drugs to treat lymphomas. When administered to patients with lymphoma, rituximab attaches to CD20, a protein found on lymphoma cells. Addition of rituximab to chemotherapy improves outcomes in many lymphoma types. A laboratory-based study by Winiarska and colleagues published this year in The Public Library of Science Medicine journal suggested that statins may inhibit rituximab binding to CD20. "That finding raised questions about maintaining or stopping cholesterol treatment with statins for patients with lymphoma," says Grzegorz Nowakowski, M.D. (mayoclinic/bio/13657551.html), Mayo Clinic hematologist and lead researcher on the Mayo study.



"One in five lymphoma patients take cholesterol-lowering statins; this corresponds to the potential for thousands of patients at risk of getting less or ineffective treatment due to statin interference with therapy," says Dr. Nowakowski. "In our prospectively followed cohort of patients, we found that statins did not interfere with rituximab and in some cases, may offer a benefit."



The Mayo Clinic study included:
228 patients with diffuse large B-cell lymphoma, an aggressive form of the disease. Twenty-two percent of this group was taking statins when they started treatment for lymphoma.


293 patients with follicular lymphoma, an often indolent and slowly progressive form of the disease. Nineteen percent of patients were taking statins.

Statins did not impinge treatment effectiveness for either group of patients. For patients with diffuse large B-cell lymphoma, statin use did not influence outcomes. Those with follicular lymphoma who took statins fared better than patients who didn't. At two years, 80 percent of those taking statins had no progression or re-treatment for their cancer versus 69 percent of those not taking statins. Dr. Nowakowski said these are early results and further validation in additional cohorts of patients is needed. This positive effect was seen regardless of the treatment approach for the lymphoma. Treatments included observation only, rituximab alone or rituximab in combination with chemotherapy medications.



Dr. Nowakowski said that while oncologists at times recommend simplifying a patient's drug regimen before starting chemotherapy, many patients simply remain on statins during treatment. "We were concerned that these patients may be at risk of receiving less effective treatment due to statin interaction with rituximab. These results can provide reassurance to oncologists and their patients that statins will not reduce the effectiveness of rituximab and may in fact improve outcomes of some patients with lymphomas," he says.







This research was a part of a large lymphoma epidemiology project at Mayo Clinic led by James Cerhan, M.D., Ph.D., and funded by University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) The broader research program seeks to translate research findings into clinical practice. (cancercenter.mayo/mayo/research/hematologic_malignancies/spore_lymphoma.cfm).



Other Mayo Clinic researchers involved in the study led by Dr. Nowakowski are: Matthew Maurer; Thomas Habermann, M.D.; Stephen Ansell, M.D., Ph.D.; William Macon, M.D.; Kay Ristow; Cristine Allmer; Susan Slager, Ph.D.; Thomas Witzig, M.D.; and Dr. Cerhan.



For more information on lymphoma treatment, please visit mayoclinic/lymphoma/.

AFFiRiS AG: Atherosclerosis Vaccine Development Receives EU Support

The atherosclerosis vaccine development program by AFFiRiS AG is receiving financial support from the EU's EUROTRANS-BIO call. The respective project is being carried out in cooperation with German company EMC microcollections GmbH. The aim of atherosclerosis vaccination is to increase the amount of "good" high density lipoprotein cholesterol (HDLc) in the blood and thus reduce the occurrence of harmful fatty deposits in the arteries. Product candidates were delivered by AFFiRiS' AFFITOME(R) platform technology. The target is a protein known as CETP (cholesteryl ester transfer protein). Following vaccines for Alzheimer's disease and Parkinson's disease, the atherosclerosis vaccine is the third such project announced by AFFiRiS AG.


Vienna-based AFFiRiS AG today announced that its atherosclerosis vaccine development program is receiving support from the EU's EUROTRANS-BIO call. The supported project - known as CETP Vaccine (ETB-2008-28) - is based on the AFFITOME(R) technology of AFFiRiS AG and is being conducted together with EMC microcollections GmbH from Tubingen, Germany. The urgent need for an effective strategy against atherosclerosis is clearly evident from the relevant figures - diseases of the cardiovascular system are the number one cause of death in Europe and the US. In Europe, this is at the root of almost 50 % of all deaths. One of the primary causes of cardiovascular disease is atherosclerosis, a narrowing of key arteries due to fatty deposits. Although there are options for medication-based intervention in the form of statins, these are deemed to be of limited effectiveness despite some notable successes.


CSO Dr. Frank Mattner explains: "Today's therapies with Statins act on low density lipoprotein cholesterol (LDLc) and reduce its concentration in the blood. This type of treatment can reduce the likelihood of severe heart disease by as little as 30 % - and that's only if the patient takes the necessary medication correctly and regularly. In contrast, our vaccine approach aims at decreasing the cholesterol transfer from HDL to LDL, thus increasing the concentration of the beneficial HDL. This vaccine approach with its long-lasting effects should avoid patients having to take life-long, daily medication to a strict regimen."


The main item of the joint efforts of AFFiRiS and EMC is the vaccination against cholesteryl ester transfer protein (CETP). By transferring cholesteryl ester from HDLc to LDLc and VLDLc, this protein reduces "good" HDL and has a detrimental impact on the ratio of LDLc to HDLc. In the future, our vaccine will reduce the activity of this protein and shift the balance of HDLc and LDLc in the blood back in favour of HDLc.















Outlining the major benefit of the AFFITOME(R) technology, project manager Dr. Sylvia Brunner adds: "CETP is one of the body's own proteins. Trying to reduce its activity using a vaccine, we are faced with a formidable challenge. The body has many means of suppressing an immune response to its own proteins, or limiting the effectiveness of any such response. That's why previous attempts to develop a vaccine against CETP failed. However, as AFFiRiS has already demonstrated in its work on a vaccine for Alzheimer's disease, the AFFITOME(R) technology makes it possible to circumvent these mechanisms. We are now applying this principle to atherosclerosis."


CEO Dr. Walter Schmidt continues: "So far, we have announced the development of vaccines for three diseases - Alzheimer's, Parkinson's and now atherosclerosis. Currently, four other indications are also part of our development pipeline, all of them characterised by a very high number of patients but also by a lack of satisfactory treatments. As a result, these indications fit in well with our long-term strategy. Our strategy itself is beginning to pay back as demonstrated by the licensing agreement worth EUR 430 million that we recently concluded with GSK Biologicals regarding the rights for the technology for our Alzheimer's vaccine programs."


The CETP Vaccine project is scheduled to last 30 months and is due to culminate in phase I clinical trials. Overall, the support provided to the project by the EU is worth several hundred thousand euros, while the two project partners are bearing around half of the total costs.


About AFFiRiS AG (as at May 2009):


AFFiRiS AG develops customised peptide-based vaccines based on its own patents. These are used to treat Alzheimer's disease, atherosclerosis, Parkinson's disease and other diseases that urgently require a medical solution and for which the market volumes are highly attractive. Alzheimer's disease is currently the foremost indication and two potential products are in the final stages of clinical phase I studies. In October 2008, the company succeeded in gaining GlaxoSmithKline Biologicals as its licensing partner for the Alzheimer's vaccine. The contract foresees payments of up to EUR 430 million (these payments are dependent on certain milestones). AFFiRiS currently employs 50 highly-qualified staff and recently acquired an additional 1,100 square meters of premises at the St. Marx campus in Vienna, Austria.

Toward Improved Forms Of A Time-tested Cholesterol-fighter

New discoveries offer promise for developing drugs that improve on the therapeutic profile of niacin, the inexpensive, time-tested B-vitamin that boosts levels of HDL cholesterol - the "good" cholesterol with the potential to protect people against heart attacks and stroke, scientists reported recently.



Graeme Semple, Ph.D., Vice President of Discovery Chemistry at Arena Pharmaceuticals, San Diego, Calif., described new insights into developing drugs that raise HDL via the same mechanism as niacin in a report presented at the 233rd national meeting of the American Chemical Society, held here last week.



In small doses, niacin is the familiar B-complex vitamin, which helps the body metabolize or breakdown carbohydrates, fats and protein into compounds that the body needs to maintain good health. In the high doses prescribed by a physician, niacin can increase HDL by as much as 35 percent and reduce levels of artery-clogging triglycerides by 50 percent.



Doctors have known since the 1970s that niacin can reduce the risk of heart attacks and strokes, but it has not been prescribed as widely as newer and more costly medications known as statins.



"The use of niacin is limited by its side-effects, including a highly uncomfortable skin flushing, which contributes significantly to poor patient compliance," Semple explained. "Since currently marketed cholesterol drugs have a more modest HDL-raising activity than niacin, better tolerated HDL-targeted therapies with improved efficacy could provide additional clinical benefits to patients and potentially reduce the risk of heart attack and stroke."



Semple described research toward that goal, including Arena's discovery of a niacin receptor termed GPR109a. It is among a family of so-called G protein-coupled receptors (GPCRs) that have long been considered among scientists as good targets for the development of new drugs.



Molecules termed ligands from the environment outside cells bind with these receptors, which are located on the cell surface. Ligands activate the GPCRs, signaling biochemical machinery inside the cell to either inhibit or accelerate cellular processes.



Niacin activates GPCRs on fat cells, signaling the cells to stop producing fatty acids in a way believed to raise HDL levels. It also can activate GPR109b, a closely related receptor on immune system cells. Semple believes that activation of one or both of those receptors may be responsible for niacin's beneficial effects, and the undesirable side effects.



Semple said data from the joint Arena-Merck research program reinforces the hypothesis that it may be possible to identify a compound that activates the niacin receptor without causing flushing, thereby separating the beneficial effects on fatty acids from the flushing side effect.



"This work has not been reported previously and has been carried out within the last three years," Semple noted. "In addition, no other pharmaceutical companies have reported on new compounds for these targets in the open literature, although some patents have appeared."







The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.



The paper on this research, MEDI 224, was presented at 10:05 a.m., Tuesday, March 27, at McCormick Place Lakeside, Room E353 A/B, Level 3, during the symposium, "Mechanistic Approaches to Increasing High Density Lipoprotein Cholesterol."



Graeme Semple, Ph.D., is Vice President of Discovery Chemistry at Arena Pharmaceuticals, San Diego, Calif.



- Michael Woods



Contact: Charmayne Marsh

or Michael Bernstein

American Chemical Society

High Cholesterol Levels Affect Mobilisation Of Cells From The Bone Marrow Implications For Transplants And Understanding Cancer Onset

Increased cholesterol levels are being increasingly recognised as risk factors for the onset and progression of several cancers. Now researchers in Portugal show that high levels of cholesterol can affect the microenvironment of the bone marrow, so that more cells move from the bone marrow to peripheral, circulating blood. These findings, by Sergio Dias and his team, an external group of the Instituto Gulbenkian de Ci??ncia, have implications for transplantation and further understanding bone marrow malignancies, are to appear in the next issue of the journal Blood.


Progenitors of blood cells develop in the bone marrow, where they mature in specific microenvironments, called niches, before exiting into peripheral blood, in a highly controlled fashion. It is well established that external stimuli affect these niches and therefore the production of mature blood cells. For example, patients with high cholesterol levels (hypercholesterolemia) have more peripheral blood cells and increased platelet levels (thrombocytosis). Working at the Portuguese Institute of Oncology Francisco Gentil, in Lisbon, the Neoangiogenesis group used a mouse model of hypercholesterolemia to show that cholesterol interferes with the bone marrow niche equilibrium, thus leading to increased exit from the bone marrow niche to the peripheral circulation.


These finding may have implications for transplants and bone marrow malignances. As S?©rgio Dias points out "It is the first time, as far as we are aware, that cholesterol is directly linked to mobilisation of cells in the bone marrow. In a transplant setting, we believe patients with high cholesterol may be less 'receptive', since more blood cells exit to the peripheral vessels. Therefore drugs that modulate cholesterol levels may have beneficial effects also in a transplant setting."


"Furthermore, as cholesterol empties cells from the bone marrow microenvironment, we envisage that it may create more space for malignant leukaemia cells to come into the bone marrow, thus favoring acute leukaemia expansion and spread to secondary organs", this group leader adds.


This study was carried out with support from the Portuguese national funding agency, Funda?§??o para a Ci??ncia e a Tecnologia (FCT) and GlaxoSmithKline.

CVS Caremark Data Finds More Than 50 Percent Of Adults 45 Years And Younger Are Not Adherent To Cholesterol Lowering Medications

A study released today by CVS Caremark (NYSE: CVS) found that more than 50 percent of patients under the age of 45 who are prescribed a medication to treat high cholesterol are not optimally adherent to their therapy. In fact, the data showed that 58 percent of adults between the ages of 18-34 are not taking their cholesterol lowering medications as prescribed.


According to the National Institutes of Health's National Heart, Lung and Blood Institute (NHLBI), high cholesterol affects more than 65 million Americans. Because high cholesterol does not cause symptoms, individuals may not be aware that they are at increased risk of developing heart disease or experiencing a heart attack. September is National Cholesterol Education Month, and is a good opportunity for people to get their cholesterol levels checked and take steps to lower their levels if they are high.


"This data illustrates that younger adults with high cholesterol are not taking their medication as prescribed, putting them at increased risk for developing heart disease, worsening their long term clinical outcomes and ultimately increasing the cost of their care," said Troyen A. Brennan, M.D., M.P.H., Executive Vice President and Chief Medical Officer, CVS Caremark. "CVS Caremark engages plan participants with chronic diseases, such as high cholesterol, by addressing barriers to evidence-based care. We engage patients in their care early in the process by providing disease and therapy education and help them improve medication adherence through proactive intervention and outreach."


The study examined adherence to cholesterol lowering medications by evaluating de-identified data for more than 74,000 adult patients from the CVS Caremark Health Management Claims Database who incurred claims for a cholesterol lowering medication between January 1, 2008 and December 31, 2008. All study participants were continuously eligible for pharmacy benefits for the entire evaluation period. Results found that only 42 percent of patients between the ages of 18-34 were optimally adherent to their medications with a medication possession ratio (MPR) of greater than 80 percent. In addition, among those patients aged 35-44, only 50 percent were identified as optimally adherent to their high cholesterol medication.


The CVS Caremark Proactive Pharmacy Care approach engages patients earlier with education and personalized outreach to improve adherence. The Adherence to Care solution is a mail and retail based program designed to impact patient behavior through timely interventions that include face-to-face, first fill counseling; IVR and Web refill reminders, renewals and pick-up prompts; and personalized letters about the importance of staying on a prescribed therapy sent to those patients who have stopped filling a maintenance prescription and their health care provider. The Adherence to Care program has been shown to help increase adherence to high cholesterol therapies with those members under 45 years of age who participate in the program experiencing an MPR increase of more than 9 percent.


Medication possession ratio (MPR) is the standard statistic used to measure medication adherence via pharmacy claims. MPR assesses if a patient has a sufficient quantity of medication dispensed to suggest the medication is being taken as prescribed. MPR is represented as a ratio of total days supply of medication divided by the total days in the measurement period. In this study, MPR was calculated using the DMAA methodology on pharmacy claims incurred by the study subjects. Patients with an MPR greater than or equal to 80 percent were considered optimally adherent to therapy. This analysis is an observational study only, and the results demonstrate a correlation between patients under age 45 and suboptimal adherence to cholesterol lowering medications; however, as in most observational studies, the causal nature of this relationship cannot be determined.


About CVS Caremark


CVS Caremark is the largest provider of prescriptions in the nation. The Company fills or manages more than 1 billion prescriptions annually. Through its unmatched breadth of service offerings, CVS Caremark is transforming the delivery of health care services in the U.S. The Company is uniquely positioned to effectively manage costs and improve health care outcomes through its more than 6,900 CVS/pharmacy and Longs Drugs stores; its Caremark Pharmacy Services division (pharmacy benefit management, mail order and specialty pharmacy)

Lipitor Significantly Lowered Hospitalization Costs For Patients With Heart Disease, Two New Analyses Show

Pfizer announced that Lipitor (atorvastatin calcium) Tablets (80 mg) lowered hospitalization costs by significantly reducing the risk of cardiovascular events in patients with heart disease, according to two separate economic analyses. The data were presented at the annual meeting of the American College of Cardiology.



"One of these analyses suggests that even with the availability of low cost generics, intensive Lipitor therapy is a good economic value," said Dr. Peter Lindgren, managing director of European Health Economics in Stockholm, Sweden, and lead investigator of the economic evaluation of the Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL) trial. "The economic impact of heart attacks and strokes in the U.S. alone totals more than $400 billion in medical care and lost productivity annually."



New IDEAL Health Economic Analysis


In a new post-hoc analysis of a subset of patients (n=999) in the IDEAL study that had acute coronary syndrome (i.e., had a heart attack less than two months prior to entering the study):


?· Hospitalization costs during the five-year trial were 21 percent lower for Lipitor 80 mg ($6,427 per patient) than for simvastatin 20 mg - 40 mg ($8,179 per patient).

?· This finding was due to the significant 20 percent reduction in the risk of any cardiovascular event for these patients.



Even in a low cost generic market, treatment of acute coronary syndrome patients with Lipitor 80 mg is predicted to reduce cardiovascular events at an acceptable incremental cost over simvastatin 20 mg - 40 mg.



On average in the U.S., coronary heart disease, including heart attacks, costs $ 96,467 in direct costs per patient, a stroke costs $59,429 and certain types of heart surgery cost $122,122.



"As physicians, payers and employers come under increasing pressure to reduce medical healthcare costs, this analysis provides them with additional support for offering intensive Lipitor therapy to help achieve improved and cost-effective cardiovascular outcomes for their patients," said Dr. Michael Berelowitz, senior vice president of Pfizer's global medical division.



This new analysis of patients with acute coronary syndrome is consistent with the health economic findings of the overall IDEAL trial of 8,888 patients.



Additionally, in a separate analysis of a large U.S. managed care database that was recently presented, Lipitor patients achieved a significant additional 14 percent reduction in the risk of cardiovascular events compared with patients taking simvastatin, even after adjustments for expected differences of LDL lowering based on dose.
















"Together these analyses provide additional evidence for physicians who may be considering prescribing statins interchangeably using dose adjustments," said Dr. Berelowitz.



About the Overall IDEAL Trial


IDEAL was an open-label trial of 8,888 patients who had had a previous heart attack comparing Lipitor 80 mg with simvastatin 20 mg - 40 mg. There was an 11 percent reduction in the primary endpoint, major coronary events, in Lipitor patients compared to simvastatin patients, but this difference did not reach statistical significance. Based on a secondary endpoint, Lipitor reduced the risk of heart attack by a significant 17 percent and the risk of any cardiovascular events by 16 percent compared with patients taking simvastatin 20 mg - 40 mg.



In a subset of these patients (n=999) who had had a heart attack less than two months prior to entering the study, Lipitor 80 mg reduced the risk of heart attacks by 46 percent, major coronary events by 34 percent, and any cardiovascular event by 21 percent compared with simvastatin 20 mg - 40 mg.



New Analysis of the Treating to New Targets (TNT) Trial


In a pre-specified analysis of more than 5,300 U.S. patients with stable coronary heart disease from the TNT trial:


?· Lipitor 80 mg provided significantly better clinical outcomes at almost no additional cost over five years compared with Lipitor 10 mg (the five-year cost of the 80 mg dose was $181 more).

?· This finding resulted from a significant 15 percent reduction in both cardiovascular hospitalizations and a significant 27 percent reduction in revascularizations.




About the overall TNT Trial


The five-year TNT study involved 10,000 patients with both heart disease and elevated LDL levels. In this study, patients taking Lipitor 80 mg had a significant 22 percent reduction in the risk of major cardiovascular events over and above patients taking Lipitor 10 mg. In addition, patients treated with Lipitor 80 mg had a significant 26 percent reduction in the risk of hospitalization for heart failure.



About Lipitor


Lipitor is the only statin proven to provide a combination of significant and proven cardiovascular event reductions, impressive average LDL lowering of 39 percent to 60 percent, and a well-established safety profile across a broad range of patients.



It is the most prescribed cholesterol-lowering therapy in the world, with nearly 133 million patient-years of experience. Lipitor is supported by an extensive clinical trial program involving more than 400 ongoing and completed trials with more than 80,000 patients.



Important U.S. Prescribing Information


Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL ("good" cholesterol) or smoking to reduce the risk of a heart attack and stroke, certain kinds of heart surgery and chest pain.



Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.



Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heart surgery, hospitalization for heart failure, and chest pain.



When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.



Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.



Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.



Lipitor

IMS Research Identifies Most Cost-Effective Programs To Keep Patients On Cardiovascular Therapies

The most cost-effective programs for helping patients stay on cholesterol and blood pressure-lowering medications have been identified in a comprehensive research study from IMS Health.


The research study, to appear in Value in Health, for the first time, looked at the results of programs conducted between 1972-2007 that were directed towards patients to keep them on their cholesterol and blood pressure lowering medications and identify those programs that were most successful at the lowest costs to the healthcare system.


The research found that a "self-monitoring, reminders and educational materials"- based program and a "pharmacist/nurse management" program were the most cost-effective intervention methods for prompting patients to adhere to maintaining cardiovascular medicine therapies over time.


Past studies have shown that patient adherence to cardiovascular medication treatment regimens decreases within 6 months of starting treatment. As a result, numerous intervention programs over many years have been developed at varying costs and success rates. With this research study, the value of these programs based on effectiveness and cost is clearer, which may help to guide design and implementation of adherence-improving programs going forward.


"With this study, we hope greater clarity has been provided on what have been approaches used most effectively for getting patients to stay on their cardiovascular therapies, thereby improving their health, and saving the healthcare system substantial costs related to cardiovascular disease," says Richard Chapman, Principal, Health Economics Outcomes Research (HEOR), IMS Health.


Value in Health publishes papers, concepts, and ideas that advance the field of pharmacoeconomics and outcomes research and help health care leaders to make decisions that are solidly evidence-based. The journal is published bi-monthly and has a regular readership of over 5,000 clinicians, decision-makers, and researchers worldwide.

Enzyme Inhibitor May Help Lower Cholesterol And Unclog Arteries

Atherosclerosis, the accumulation of cholesterol in the arteries that clogs the circulation and results in heart attacks and strokes, is a leading cause of death. One strategy for preventing heart disease and stroke is to clear out clogged arteries, restoring circulation. This process, known as reverse cholesterol transport is accomplished by the high-density lipoproteins (HDLs) in the blood. HDL transports excess cholesterol from the artery wall and macrophages and delivers it to the liver, where it is excreted as bile salts and cholesterol. In a study appearing in the May issue of the Journal of Clinical Investigation, Fumihiko Matsuura and colleagues from Columbia University, New York, reveal new features of this pathway that suggest an enzyme inhibitor currently in phase III clinical trials may help reduce cholesterol levels and atherosclerosis in humans.



One proposal for boosting reverse cholesterol transport has been to elevate plasma HDL levels by inhibiting a protein called CETP that transfers cholesterol esters from HDL to lower-density lipoproteins. However, there has been controversy in the medical literature as to whether CETP deficiency is pro- or anti-atherogenic. Matsuura and colleagues assessed the ability of HDL-2 from individuals deficient in CETP to promote cholesterol removal from macrophages. They observed a 2??"3-fold increase in cholesterol efflux in these individuals compared to controls and they demonstrated that this was dependent on a molecule known as ABCG1, which is present on macrophages and contributes to the formation of HDL. They also found that the enhanced ability to promote cholesterol removal in these CETP-deficient individuals was due to increased amounts of the enzyme LCAT and apolipoprotein E in HDL-2, which allow the inner cholesterol ester??"rich core of HDL-2 to expand to carry greater amounts of cholesterol. In an accompanying commentary, Robert Mahley and colleagues from the University of California, San Francisco, comment that as CETP does not appear to be essential for reverse cholesterol transport in humans, this raises the hope of using a CETP inhibitor to elevate HDL levels and therefore reduce the incidence of atherosclerosis.







TITLE: HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway



AUTHOR CONTACT:

Fumihiko Matsuura

Osaka University, Osaka, Japan.



View the PDF of this article at: https://the-jci/article.php?id=27602



ACCOMPANYING COMMENTARY



TITLE: Putting cholesterol in its place: apoE and reverse cholesterol transport



AUTHOR CONTACT:

Robert W. Mahley

Gladstone Institute of Neurological Disease, San Francisco, California, USA.



View the PDF of this article at: https://the-jci/article.php?id=28632



Contact: Brooke Grindlinger

Journal of Clinical Investigation