ACC/AHA publish new guideline for management of blood cholesterol

The American College of Cardiology and the American Heart Association today released a new clinical practice guideline for the treatment of blood cholesterol in people at high risk for cardiovascular diseases caused by atherosclerosis, or hardening and narrowing of the arteries, that can lead to heart attack, stroke or death.

13 nov 2013--The guideline identifies four major groups of patients for whom cholesterol-lowering HMG-CoA reductase inhibitors, or statins, have the greatest chance of preventing stroke and heart attacks. The guideline also emphasizes the importance of adopting a heart-healthy lifestyle to prevent and control high blood cholesterol.

"The new guideline uses the highest quality scientific evidence to focus treatment of blood cholesterol on those likely to benefit most," said Neil J. Stone, MD, Bonow professor of medicine at Northwestern University Feinberg School of Medicine and chair of the expert panel that wrote the new guideline. "This guideline represents a departure from previous guidelines because it doesn't focus on specific target levels of low-density lipoprotein cholesterol, commonly known as LDL, or 'bad cholesterol,' although the definition of optimal LDL cholesterol has not changed. Instead, it focuses on defining groups for whom LDL lowering is proven to be most beneficial."

The new guideline recommends moderate- or high-intensity statin therapy for these four groups:

• Patients who have cardiovascular disease;
• Patients with an LDL, or "bad" cholesterol level of 190 mg/dL or higher;
• Patients with Type 2 diabetes who are between 40 and 75 years of age; and
• Patients with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75 years of age (the report provides formulas for calculating 10-year risk).

In terms of clinical practice, physicians can use risk assessment tools in some cases to determine which patients would most likely benefit from statin therapy, rather than focusing only on blood cholesterol to determine which patients would benefit.

"The likely impact of the recommendations is that more people who would benefit from statins are going to be on them, while fewer people who wouldn't benefit from statins are going to be on them," Dr. Stone said. Doctors may also consider switching some patients to a higher dose of statins to derive greater benefit as a result of the new guidelines.

The guideline was prepared by a panel of experts based on an analysis of the results of randomized controlled trials. The panel was charged with guiding the optimal treatment of blood cholesterol to address the rising rate of cardiovascular disease, currently the leading cause of death and disability in the U.S.

The panel chose to focus on the use of statins after a detailed review of other cholesterol-lowering drugs. "Statins were chosen because their use has resulted in the greatest benefit and the lowest rates of safety issues. No other cholesterol-lowering drug is as effective as statins," said Dr. Stone. He added that there is a role for other cholesterol-lowering drugs, for example, in patients who suffer side effects from statins.

The report also stresses the importance of lifestyle in managing cholesterol and preventing heart disease. "The cornerstone of all guidelines dealing with cholesterol is a healthy lifestyle," said Dr. Stone. "That is particularly important in the young, because preventing high cholesterol later in life is the first and best thing someone can do to remain heart-healthy. On the other hand, if someone already has atherosclerosis, lifestyle changes alone are not likely to be enough to prevent heart attack, stroke, and death, and statin therapy will be necessary."

In addition to identifying patients most likely to benefit from statins, the guideline outlines the recommended intensity of statin therapy for different patient groups. Rather than use a "lowest is best" approach that combines a low dose of a statin drug along with several other cholesterol-lowering drugs, the panel found that it can be preferable to focus instead on a healthy lifestyle along with a higher dose of statins, eliminating the need for additional medications.

"The focus for years has been on getting the LDL low," said Dr. Stone. "Our guidelines are not against that. We're simply saying how you get the LDL low is important. Considering all the possible treatments, we recommend a heart-healthy lifestyle and statin therapy for the best chance of reducing your risk of stroke or heart attack in the next 10 years."

The guidelines are intended to serve as a starting point for clinicians. Some patients who do not fall into the four major categories may also benefit from statin therapy, a decision that will need to be made on a case-by-case basis. The expert panel that wrote the report was convened by the National Heart, Lung, and Blood Institute of the National Institutes of Health. At the invitation of the NHLBI, the American Heart Association and American College of Cardiology assumed the joint governance, management and publication of this guideline, along with four other prevention guidelines, in June. Committee members volunteered their time and were required to disclose all healthcare-related relationships, including those existing one year before the initiation of the writing project.

More information: The full text of the report, "2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults," will be published in future print issues of the of the Journal of the American College of Cardiology and the American Heart Association's journal Circulation. It will also be accessible today on the ACC website and AHA.

Provided by American College of Cardiology

Larger study confirms statins' role in preventing cardiac events

A large and unselected community-based study has confirmed the results of randomized controlled trials that have found persistent statin use to be beneficial for the primary prevention of acute cardiac events; the study was published online Sept. 27 in The American Journal of Cardiology.

08 oct 2012—A large and unselected community-based study has confirmed the results of randomized controlled trials that have found persistent statin use to be beneficial for the primary prevention of acute cardiac events; the study was published online Sept. 27 in The American Journal of Cardiology.

Varda Shalev, M.D., from Tel Aviv University in Israel, and colleagues examined the effectiveness of statins in primary prevention of acute nonfatal cardiac events in the community setting. Data were analyzed from a cohort of 171,535 adults aged 45 to 75 years, without cardiovascular disease, who were given statins between 1998 to 2009 in a large health maintenance organization in Israel.

The researchers found that the incidence of acute cardiovascular events during the 993,519 person-years of follow-up was 10.22 per 1,000 person-years. Persistence with statins correlated with significantly reduced risk of incident cardiac events. There was a hazard ratio of 0.58 for the most persistent users (covered with statins for 80 percent or more of their follow-up time) compared with non-persistent users (less than 20 percent of days covered). When the analyses were limited to patients with more than five years of follow-up, the results were similar. Treatment with high efficacy statins correlated with a reduced risk of cardiac events.

"In conclusion, our large and unselected community-based study supports the results of randomized controlled trials regarding the beneficial effect of statins in the primary prevention of acute cardiac events," the authors write.

More information: Abstract 
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New study supports statin's anti-dementia effects

NEW YORK, 09 jan 2009– In the largest cohort study to date, treatment with a cholesterol-lowering statin drug was found to reduce new cases of Alzheimer's disease, regardless of the specific type of statin used or a person's genetic risk for the disease.

Numerous studies have looked at the relationship between statin use and the development of Alzheimer's disease, with conflicting results. One explanation for the inconsistencies is that only the fat soluble or "lipophilic" statins, which could get into the brain more easily than water soluble or "hydrophilic" statins, were included in the studies.

To explore these issues, Dr. M. M. B. Breteler and colleagues at the Erasmus Medical Center in Rotterdam, the Netherlands, analyzed data from the prospective, population-based Rotterdam Study. The analysis included 6992 subjects, 55 years old or older, who were free of dementia when examined between 1990 and 1993.

During follow-up until 2005 (an average of 9.2 years), 582 subjects were diagnosed with Alzheimer's. After controlling for social, demographic and clinical factors that might raise a person's risk of getting the disease, statin users had a significant 43 percent reduced risk of Alzheimer's disease compared with those who never used statins.

The protective effect was similar for fat soluble and water soluble statins. Examples of fat soluble statins are atorvastatin (Lipitor), simvastatin (Zocor), lovastatin (Mevacor), or fluvastatin (Lescol). An example of a water soluble statin is pravastatin (Pravachol).

The protective effect of statin use against Alzheimer's disease was also similar for persons with and without the major gene mutation associated with an increased risk of Alzheimer's disease (i.e., the apolipoprotein E-epsilon-4 allele).

On the other hand, the use of other cholesterol-lowering drugs such as fibrates or nicotinic acid failed to exhibit similar benefit, Breteler's team reports.

The findings appear in this month's issue of the Journal of Neurology, Neurosurgery and Psychiatry.

In a commentary published with the study, Dr. Larry Sparks at the Sun Health Research Institute in Sun City, Arizona, states: "All in all, it is clear that somewhere between normal cognitive performance and profound dementia of Alzheimer's disease, statin therapy exerts a beneficial effect."

He points out that nearly 20 previous studies have assessed the effect of statin use on later risk of Alzheimer's disease in older people, and the majority found substantial benefit.

Sparks concludes that "it is our task to identify at what point in time statin therapy might be of the greatest benefit in order to effectively target which patients to treat with cholesterol-lowering statins."

SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, January 2009.

MSU researcher studies ties between cholesterol drugs, muscle problems

Evidence suggests statins can cause muscle weakness, fatigue and deterioration

EAST LANSING, Mich., 13 nov 2008— A Michigan State University researcher is studying whether the most popular class of cholesterol-lowering drugs may cause muscle problems in users.

There is accumulating evidence that the effect statins can have on skeletal muscle – including muscle weakness, fatigue and deterioration – is underestimated, said Jill Slade, assistant professor of radiology and osteopathic manipulative medicine at MSU.

"Statins work by preventing cholesterol from forming," said Slade, whose study is funded by a two-year, $230,000 grant from the National Institutes of Health. "While this is a good thing inside structures such as liver cells, it can be problematic in places such as muscle cells."

About 50 percent of all Americans over the age of 50 are prescribed a statin medication, including Lipitor, Crestor and Torvast, and their use has tripled in the past seven years. Side effects affecting skeletal muscles have been reported in up to 7 percent of users, though Slade thinks that number could be higher.

In August 2001, the Food and Drug Administration pulled the statin Baycol off the market after it appeared to be responsible for 31 deaths through a potentially fatal breakdown of muscle tissue known as rhabdomyolysis. The FDA at the time said the muscle breakdown occurred more frequently in patients taking Baycol than in patients on other statins. The National Lipid Association in 2006 published recommendations on investigating statin-induced muscle problems, and Slade's research will directly address several of those.

As part of her study, Slade will use nuclear magnetic resonance imaging at the MSU Department of Radiology Exercise and Nutrition Lab to measure muscle integrity and function before and during statin treatment. Fifty people – half taking high doses of statins and half taking low doses – will be analyzed over a one- to six-month period.

"While statins have tremendously helped millions of Americans lower their cholesterol and improve their cardiac health, we need to be confident we are not causing other problems in the body," Slade said. "It is important to understand the side effects of using statins and have the tools to identify people who may be more susceptible to them."

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ESC: Statin Therapy Reduces Perioperative Cardiac Events

By Ed Susman
MUNICH, 07 sept 2008-- Extended-release fluvastatin (Lescol) -- given to patients just before undergoing vascular surgery and continued for a month -- reduced the relative risk of suffering a heart attack by a significant 47%, Dutch researchers reported here. "Perioperative extended-release fluvastatin use might be recommended in vascular surgery patients," suggested Don Poldermans, M.D., of Erasmus University in Rotterdam, at the European Society of Cardiology meeting. Treatment was started at the outpatient clinic on the day of randomization, a median 37 days prior to the surgical procedure, and was continued at least during the first 30 days after surgery. The primary analysis was intention-to-treat and involved all patients who were randomly assigned to either fluvastatin or placebo. Directly after surgery, study treatment was temporarily discontinued in 115 (23%) patients for a median duration of two days because of the inability to take the study drug orally.
A total of 34 patients discontinued the study medication because of laboratory abnormalities, 16 (3.2%) because of alanine aminotransferase exceeding three times the upper limit of normal, 13 (2.6%) because of creatinine kinase exceeding 10 times theupper limit of normal, and five (1%) because of a combination of elevated alanine aminotransferase and CK.
Dr. Poldermans said that myocardial ischemia occurred in 10.6% of the 250 patients assigned to fluvastatin compared with 18.2% of the 247 patients who were randomly assigned to receive placebo in the study (OR 0.53, 95% CI 0.32 to 0.88, P=0.016). The number needed to treat to prevent one patient experiencing myocardial ischemia was 12.5 patients.
In addition, he said that after 30 days of the trial period, 12 (4.8%) of the patients on fluvastatin achieved the secondary endpoint of cardiovascular death and/or nonfatal myocardial infarction compared with 25 (10.1%) of patients on placebo (OR 0.48, 95% CI 0.24 to 0.95, P=0.039).
In reporting the results of the Dutch Echographic Cardiac Risk Evaluating Applying Stress Echo III (DECREASE) trial, Dr. Poldermans noted that the use of 80 mg of extended-release fluvastatin in the patients just prior to surgery and until 30 days after the vascular surgery was not accompanied by an increase in adverse side effects, liver dysfunction, or myopathy compared with placebo.
"This therapy was associated with improved postoperative cardiac outcome in high-risk patients undergoing elective vascular surgery," he said.
"The results of DECREASE are a good demonstration of the benefits of statins beyond their ability to reduce cholesterol," commented Timothy Gardner, M.D., director of the Heart and Valvular Institute for Christiana Care, Wilmington, Del., and president of the American Heart Association. He said the patients were undergoing aortic surgery or peripheral vascular surgery.
Dr. Gardner said fluvastatin is not used widely in the United States so he anticipated that other companies that make statins were likely to attempt to replicate the results of DECREASE.
Dr. Poldermans said his group employed fluvastatin in the trial not to reduce cholesterol, but to make use of the purported pleiotropic effects of statins -- in particular the drugs' known ability to reduce inflammatory responses that occur in surgical scenarios.
He noted that about 2% of patients undergoing noncardiac vascular surgery die from cardiac causes during the perioperative period. He said that causes of perioperative myocardial infarction are complex but one theory suggests that coronary plaque instability leading to plaque rupture and thrombosis is a significant problem. He said the trial aimed at assessing the cardioprotective effect of fluvastatin on top of beta-blocker therapy in vascular surgery patients.
"What we have learned from the DECREASE study," said Elliot Antman, M.D., of Harvard Medical School, Boston, and another spokesperson for the American Heart Association, "is that there may be additional medical benefits of starting the statins early."
Neither Dr. Gardner nor Dr. Poldermans had any disclosures. Dr. Antman disclosed relationships with Merck & Co., Inc., Bristol-Myers Squibb Pharmaceutical Research Institute, sanofi-aventis, Millennium Pharmaceuticals, Nuvelo Inc., AstraZenaca Pharmaceuticals LP, CV Therapeutics, Inotek Pharmaceuticals Corporation, Eli Lilly and Company, Schering-Plough Research Institute, Integrated Therapeutics Corporation, Bayer Healthcare LLC, Ortho-Clinical Diagnostics, Inc., Sanofi-Synthelabo Recherche, GlaxoSmithKline, Amgen Inc., Beckman Coulter, Inc., Biosite Incorporated, Roche Diagnostics Corporation, Roche Diagnostics GmbH, Pfizer, Inc., Accumetrics, Inc., the National Institutes of Health, and Novartis Pharmaceuticals.
Primary source: European Society of CardiologySource reference:Poldermans D, et al "Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery: Results form a randomizxed placebo controlled trial" ESC 2008.