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Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis
Stephen J. Nicholls, MBBS, PhD; E. Murat Tuzcu, MD; Ilke Sipahi, MD; Adam W. Grasso, MD; Paul Schoenhagen, MD; Tingfei Hu, MS; Kathy Wolski, MPH; Tim Crowe, BS; Milind Y. Desai, MD; Stanley L. Hazen, MD, PhD; Samir R. Kapadia, MD; Steven E. Nissen, MD
JAMA. 2007;297:499-508.
Context Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary atherosclerosis. However, no data exist describing the relationship between statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and disease progression.
Objective To investigate the relationship between changes in LDL-C and HDL-C levels and atheroma burden.
Design, Setting, and Patients Post-hoc analysis combining raw data from 4 prospective randomized trials (performed in the United States, North America, Europe, and Australia between 1999 and 2005), in which 1455 patients with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or for 24 months. Ultrasound analysis was performed in the same core laboratory for all of the studies.
Main Outcome Measure Relationship between changes in lipoprotein levels and coronary artery atheroma volume.
Results During statin therapy, mean (SD) LDL-C levels were reduced from 124.0 (38.3) mg/dL (3.2 [0.99] mmol/L) to 87.5 (28.8) mg/dL (2.3 [0.75] mmol/L) (a 23.5% decrease; P<.001), and HDL-C levels increased from 42.5 (11.0) mg/dL (1.1 [0.28] mmol/L) to 45.1 (11.4) mg/dL (1.2 [0.29] mmol/L) (a 7.5% increase; P<.001). The ratio of LDL-C to HDL-C was reduced from a mean (SD) of 3.0 (1.1) to 2.1 (0.9) (a 26.7% decrease; P<.001). These changes were accompanied by a mean (SD) increase in percent atheroma volume from 39.7% (9.8%) to 40.1% (9.7%) (a 0.5% [3.9%] increase; P = .001) and a mean (SD) decrease in total atheroma volume of 2.4 (23.6) mm3 (P<.001). In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-HDL cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely correlated with atheroma progression. In multivariate analysis, mean levels of LDL-C ( coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C ( coefficient, –0.26 [95% confidence interval, –0.41 to –0.10]) remained independent predictors of atheroma regression. Substantial atheroma regression (5% reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; P<.001). No significant differences were found with regard to clinical events.
Conclusions Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by more than 7.5%. These findings suggest that statin benefits are derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C, although it remains to be determined whether the atherosclerotic regression associated with these changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical outcomes.

high dose statin therapy
Throughout the period from 2004 to 2006, the results of a series of clinical trials have been presented, demonstrating the efficacy of high-dose statin therapy in various patient populations. These results were all presented in the context of consensus recommendations that the target level for low-density lipoprotein (LDL)-cholesterol should be 130 mg/dL, and in patients at particular risk, the goal should be 100 mg/dL. The results of these trials have demonstrated 2 important points:
First, that it is possible to safely achieve much lower LDL-cholesterol levels with a regimen of high-dose statin therapy; and
Second, that these lower achieved LDL-cholesterol levels will result in significantly fewer clinical events.

The first of these major trials was Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT-TIMI 22),[1] comparing "standard" statin therapy (pravastatin 40 mg/day) vs more-intensive statin therapy (atorvastatin 80 mg/day) in more than 4000 patients with acute coronary syndrome (ACS). The mean LDL-cholesterol level achieved was 62 mg/dL, and there was a highly significant decrease in the primary composite endpoint of all-cause mortality, myocardial infarction (MI), unstable angina requiring hospitalization, or stroke, which was seen as early as 30 days and continued throughout the 2 years of follow-up.

The conceptually similar Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trial[2] assessed a "standard" simvastatin dose of 20 mg/day or to a high-dose statin regimen of 80 mg/day atorvastatin, but this time in 8888 patients with coronary artery disease (CAD). After a mean follow-up of 4.8 years, LDL-cholesterol levels were reduced at 1 year by 33% in the simvastatin group (to a mean of 104 mg/dL) and by 47% in the atorvastatin group (to a mean of 81 mg/dL). Although the reduction in the primary endpoint was not statistically significant, a statistically significant 17% reduction was seen in one of the individual components, nonfatal MI.

The largest of these trials was the Treating to New Targets (TNT) study,[3] which was a large international clinical trial designed to compare secondary prevention with intensive vs moderate lipid lowering using different doses of the same statin, 10 mg vs 80 mg daily of atorvastatin in patients with documented CAD.
The trial randomized 10,000 subjects with baseline LDL-cholesterol levels of 130-250 mg/dL and triglyceride levels < 600 mg/dL. All patients were initially enrolled into an 8-week run-in period of 10 mg/day atorvastatin. Those who met all other study criteria, achieved an LDL-cholesterol level ¡Ü 130 mg/dL during the run-in period, and did not have an adverse reaction to the drug were randomly assigned to:
Continue on 10 mg/day atorvastatin daily, or
Increase to 80 mg/day atorvastatin.
The study was double-blinded so that neither the subjects nor the medical staff caring for them knew which dose regimen the patients were on, nor did they know any of their lipid levels during the course of the study.
Lipid results: During the course of the study, LDL-cholesterol remained at approximately the baseline level in the 10-mg group and fell to roughly 77 mg/dL in the 80-mg atorvastatin group. Baseline triglyceride levels were approximately 150 mg/dL overall and decreased in both groups during the course of the study to about 130 mg/dL. The high-density lipoprotein (HDL)-cholesterol level was 47 mg/dL at baseline and stayed virtually the same throughout the study in both groups.
Endpoint results: At the end of the study (5-year follow-up), each of the individual components of the endpoint -- cardiovascular death, MI, and stroke -- was significantly reduced by approximately 20% compared to the control 10-mg/day group. The relative risk of the primary outcome measure (fatal or nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke) was reduced by 22% in the 80-mg atorvastatin compared with the 10-mg atorvastatin group (P < .001). The relative risk of stroke alone was 23% lower in the 80-mg atorvastatin group vs the 10-mg group, and the relative risk of hospitalization for congestive heart failure was 26% lower in the patients on 80 mg
In sum, the only really clinically significant change in lipids in the TNT study was the significant decrease in the LDL-cholesterol levels. This aggressive LDL-cholesterol lowering, to levels well below those recommended for patients with documented CAD, was associated with a dramatic decrease in major cardiovascular events. This benefit was slightly, but probably not significantly, greater in patients with diabetes or metabolic syndrome than in the overall group.
It should be emphasized that the impressive results in TNT were obtained in subjects with mean baseline LDL-cholesterol levels that were already fairly low, at about 100 mg/dL. Thus, TNT provides strong evidence that even in diabetic and metabolic syndrome patients who present with LDL-cholesterol levels in the low 100s, there is measurable and significant added benefit to be gained by lowering LDL-cholesterol to levels in the mid-70s with high-dose statin therapy. In addition, the incidence of side effects of this intensive therapy in both diabetic and metabolic syndrome patients was quite low


September 25, 2006 03:57:05 PM PST
Early, aggressive treatment with cholesterol-lowering statin drugs gives significant long-term benefits for people who suffer heart attacks or other acute coronary events, a new study of studies shows.
"We found that if you gave someone with an acute coronary syndrome statin treatment, it reduced the incidence of heart attacks and other cardiac events over the next two years by more than 18 percent," said Dr. Jeffrey Jackson, program director of the general medicine fellowship program at Walter Reed Army Medical Center, in Washington, D.C.
Jackson and his colleagues analyzed the results of 13 previous studies in which intensive statin therapy was or was not begun for nearly 18,000 patients within 14 days of hospitalization for an acute coronary syndrome. They found major benefits for those getting aggressive statin treatment, compared to patients who received low-dose or no statin treatment.
The findings were published in the Sept. 25 issue ofArchives of Internal Medicine.
"These benefits took more than four months to begin to accrue and were sustained for two years," the researchers wrote. "During those two years, there was slightly less than a 20 percent reduction in the risk of experiencing an adverse cardiac event."
Part of the benefit is due to something other than the cholesterol-lowering effect of statins, the researchers said. The drugs also reduce inflammation, lower blood pressure, improve blood-vessel function and stabilize the build-up of artery-clogging plaque, they noted.
A report being published this week in the journal Circulation supports that view, said Dr. Robert A. Stein, director of preventive cardiology at Beth Israel Medical Center in New York City and a spokesman for the American Heart Association.
In that report, Italian cardiologists described a major reduction in the incidence of atrial fibrillation, a dangerous abnormal heartbeat, in people given statins before bypass surgery.
Both Jackson and Stein said the view that intensive statin therapy is beneficial for acute coronary syndrome has strengthened as more study results become available.
"Most people are in tune with the notion that you want to reduce cholesterol in such cases," Jackson said. "Increasingly, the belief in how much you want to reduce cholesterol has changed over the years. First you wanted to get below 160, then below 130, then below 100, then to 70. Now you want to be aggressive, give high doses early and don't wait."
"In almost every acute coronary syndrome, more is better," Stein said of statin therapy.
Fear of possible severe side effects of intensive statin therapy has lessened considerably, the Walter Reed study said. Rates of such side effects as hepatitis were similar in those getting or not getting intensive treatment and "serious adverse effects were rare," they noted.
Acute coronary syndrome patients who aren't candidates for statin treatment because of allergy or other complicating factors should be treated intensively with other cholesterol-lowering drugs, Stein said.

Lipitor for Pneumonia?  Mon Jul 25, 7:02 PM ET

MONDAY, July 25 (HealthDay News) -- Cholesterol-busting drugs called statins can also reduce the risk of death by pneumonia in hospitalized patients, according to a study in the journal Respiratory Research.

Researchers found that pneumonia patients who were taking a statin (which include drugs such as Lipitor, Pravachol, and Zocor) when they entered the hospital were 2.8 times less likely to die than patients who were not on these drugs.

Statins are known to affect the immune system, and that could explain their effect on pneumonia patients, speculate researchers from the University of Texas Health Science Center at San Antonio.

Pneumonia is the leading cause of death from infection in the United States, killing up to 40,000 people every year.

Coenzyme Q10 Lessens Muscle-Related Side Effects in Patients on Statins"
By Jill Stein ORLANDO, FL -- March 7, 2005 -- Patients with significant myopathy who are taking statin therapy have a significant decrease in myopathic pain after 30 days of supplementation with coenzyme Q10, according to results presented here on March 6[th at the American College of Cardiology 54th Annual Scientific Session.

Patricia Kelly, DO, Associate Professor of Medicine, University Hospital Medial Center, Stony Brook, New York, United States, randomized in a double-blind design 41 statin-treated patients with myopathic pain to 30 days of supplementation with 400 IU of vitamin E or 100 mg daily of coenzyme Q10.

"Statin treatment markedly reduces [the incidence of] cardiac events and mortality," Dr. Kelly said. "However, the reported side effects of treatment include myopathy, muscle damage associated with increased levels of creatinine phosphokinase, and abnormalities of liver function."

The researchers conducted the present trial to determine if coenzyme Q10 supplementation would improve muscle related adverse effects in patients on statins. "If coenzyme Q10 supplementation were effective in reducing the symptoms of myopathy associated with statin use, it would be possible for patients to retain the beneficial effects of cholesterol lowering while reducing significant side effects," she added.
The two treatment groups were similar with respect to demographic and clinical parameters.

Pre- and post- vitamin E, pain remained unchanged (3.9 versus 4.4, P = NS). Pre- and post coenzyme Q10, pain improved significantly (6.2 1.7 versus 3.1, P <.001).

Pain improved in three of 20 vitamin E patients and 18 of 21 coenzyme Q 10 patients (P <.001).

There was no significant change in creatinine phosphokinase with treatment in either group nor did these levels correlate with pain severity.

Coenzyme Q10 did not have any effect on lipid levels and was safe and well tolerated.

"This study provides encouraging evidence for the use of coenzymeQ10 in alleviating myopathic pain in patients taking statins," Dr. Kelly said.

strengths include the 100% compliance rates, randomized blinded design, use of validated pain scale, and duration of treatment of 4 weeks to ensure adequate absorption of coenzyme Q10, she added.

Statin Therapy May Reduce Progression of Heart Disease in Children and Teens With High Cholesterol

Before your child's birth, maybe you dreamed of passing on your love of sports or the red hair that runs in your mother's family - but you probably didn't hope to pass on your high cholesterol. Children and teens whose parents have high cholesterol can inherit a higher risk of developing thickened arteries and eventually heart disease. Statin therapy - treatment with a type of cholesterol-lowering drug - has proven effective in reducing cholesterol levels in adults, but does it work in kids and teens?

Researchers from the University of Amsterdam and the University of Rotterdam, both in the Netherlands, studied the effectiveness of statin therapy in a group of 214 8- to 18-year-olds who had high cholesterol. All of the children in the study had a parent with high cholesterol, had eaten a fat-restricted diet for the previous 3 months, and were exercising regularly. Half of the children were randomly assigned to take a statin drug daily; the rest of the children took a placebo (inactive drug) that looked similar to the statin drug. The children recorded their food intake and physical activity levels and underwent checkups every 6 months during the 2-year study. The children also regularly had blood studies monitored and imaging tests done to check for changes in their hearts and cardiovascular systems.

The imaging studies showed that children who took the statin drugs tended to have reductions in the thickness of the arteries in the heart (thickened arteries are a risk factor for cardiovascular disease) - whereas children who took the placebo drug tended to have artery thickening as the study progressed. In addition, the statin drugs significantly reduced the children's levels of LDL cholesterol ("bad" cholesterol), compared to those children treated with the placebos.

What This Means to You: Statin therapy proved safe and effective in this short-term study of a group of Dutch children and teens with inherited high cholesterol, however, the researchers of this study point out that more research into statin therapy for kids and teens is needed. Eating a healthy diet that's low in fat, getting plenty of physical activity, and maintaining a healthy weight are the mainstays for maintaining heart health in both kids and adults. If your family has a history of high cholesterol, talk to your child's doctor about whether your child should be tested for the condition.

Source: Albert Wiegman, MD, PhD; Barbara A. Hutten, PhD; Eric de Groot, MD, PhD; Jessica Rodenburg, MD; Henk D. Bakker, MD, PhD; Harry R. Büller, MD, PhD; Eric J. G. Sijbrands, MD, PhD; John J. P. Kastelein, MD, PhD; Journal of the American Medical Association, July 21, 200
Reviewed by: Steven Dowshen, MD
Date reviewed: September 2004

Crestor Drug Beats Lipitor in Study  Mon Sep 6, 6:56 AM ET
  LONDON (Reuters) - AstraZeneca Plc's cholesterol-lowering drug Crestor performed better than Pfizer Inc's Lipitor (news - web sites) in an AstraZeneca-funded study of patients with metabolic syndrome, according to results released on Monday.

Metabolic syndrome covers a cluster of risk factors that predispose people to diabetes and heart disease, including obesity, high blood pressure, high blood sugar, high blood fat levels and low levels of beneficial HDL cholesterol.

Nearly a quarter of adults in the West have the condition.

The 400-patient clinical trial found that patients with metabolic syndrome given 20 milligrams a day of Crestor had a 49 percent reduction in levels of harmful LDL cholesterol levels after 12 weeks of treatment while their HDL increased 10.5 percent. Those on the same dose of Lipitor had a 43 percent decline in LDL and only a 5.7 percent increase in HDL, according to findings presented at the annual meeting of the European Association for the Study of Diabetes in Munich.

"Results from this study show that Crestor is an effective medication for this higher-risk patient group," said Dr Christie Ballantyne of Baylor College of Medicine in Houston, one of the study investigators.

AstraZeneca, which launched Crestor last year, is battling for market share against Lipitor, which with annual sales running at some $10 billion dominates the lucrative cholesterol drug market.

Cholesterol medicines are the biggest sellers in the world, with aggregate sales totaling $24.7 billion in the 12 months to June, according to healthcare consultancy IMS Health.
AstraZeneca's Crestor has so far taken only a small part of that market, with sales in the second quarter of 2004 totaling $207 million, but the Anglo-Swedish firm is aiming to secure a 20 percent share.

Part of its strategy involves conducting a large number of post-launch clinical studies, which are designed to prove the effectiveness of Crestor and lay to rest concerns about possible adverse side effects.

The latest study is part of much larger project. So far, three studies in the so-called Galaxy clinical trials program have been completed and 14 studies are ongoing, which have in total recruited more than 40,000 patients.

AstraZeneca said the latest study, known as Comets, showed Crestor to be well tolerated, with a rate of adverse events similar to that seen with Lipitor.

Cholesterol-Lowering Drugs Cut Glaucoma Risk
CHICAGO (Reuters) - Cholesterol-lowering drugs such as statins appear to reduce the risk of developing the most common type of glaucoma, a leading cause of blindness, researchers said on Monday.

Statins, which are prescribed for heart patients to reduce how much cholesterol the body makes, have previously been shown to cut the risk of age-related macular degeneration, a condition that affects the eye's retina that is the leading cause of blindness in most industrialized countries.
The latest study, published in the June issue of The Archives of Ophthalmology, compared a group of men over age 50 diagnosed with glaucoma with a group that had not been diagnosed and found a significant reduction in risk when cholesterol-fighting drugs had been used over a long period.

The drugs were found to reduce the incidence of open-angle glaucoma, in which the eye's drainage canals become clogged and pressure builds in the eyeball, causing damage to the optic nerve.

Open-angle glaucoma afflicts roughly 3 million Americans, half of whom are undiagnosed and may not know they have it. Glaucoma robs people of sight with little warning and, while it can be treated with medications and surgery in early stages, there is no cure once blindness sets in.

All types of cholesterol-lowering drugs, including statins, appeared to help reduce the incidence of open-angle glaucoma, said study author Gerald McGwin of the University of Alabama at Birmingham.

Recent research has also indicated long-term use of statins may also prevent various forms of cancer, including prostate and colon cancer, though the drugs have not been approved for such use.

Studies Suggest Statins Slash Cancer Risk
By Ransdell Pierson

NEW ORLEANS (Reuters) - Cholesterol-lowering drugs called statins may prevent various forms of cancer, including prostate and colon cancer, two teams of researchers said on Sunday.

Israelis who took statins had a 51 percent lower risk of developing colon cancer than those who did not take the drugs, Dr. Stephen Gruber of the University of Michigan told a meeting of the American Society of Clinical Oncology (news - web sites).

A second study at Oregon Health & Science University Cancer Institute showed that men who took statins had a 58 percent lower risk of prostate cancer.

Combined, the studies suggest that statins, which reduce how much cholesterol the body makes, may also affect some the of the processes that underlie cancer.

But Gruber warned his study was "observational," or based on questionnaires rather than strict scientific controls, so it is far too early to definitively conclude that statins can prevent cancer.

His team studied 3,342 Israeli patients, about half of them with colorectal cancer, comparing them to a similar number of people matched for age, gender, and ethnicity.

They were all asked whether they had taken a statin for at least five years.

Statins greatly reduce the risk of stroke and heart attack and may help patients with multiple sclerosis and even Alzheimer's disease (news - web sites).

Statins -- which include Pfizer Inc.'s $10 billion-a-year Lipitor (news - web sites), Bristol-Myers Squibb Co.'s Pravachol and Merck and Co. Inc.'s Zocor -- interfere with an enzyme called HMG-CoA reductase that enables the liver to produce cholesterol.

In laboratory studies they also interfered with the growth of cancer cells.

"Pravastatin (Pravachol) and simvastatin (Zocor) had similarly protective effects" against colorectal cancer," Gruber said, suggesting all members of the statin class somehow interfere with development of tumors.

Gruber said other types of medicines that help control buildup of artery-clogging fats did not appear to have reduced the cancer risk.

He speculated statins, besides cutting cholesterol production, also interfere with a number of genes that promote tumors and therefore probably protect against other forms of cancer.

Oregon Health & Science University researcher Jackilen Shannon agrees.

"We were interested in the relationship between statin use and prostate cancer because recent research has demonstrated that in a number of tumor types, statins also induce cancer cell death and growth arrest," Shannon said in a statement.

"If these results are confirmed in a larger prospective study, they may provide necessary evidence to consider the use of cholesterol-lowering drugs in prostate cancer prevention. Currently, no preventive measures are available for prostate cancer."

Her team reviewed the records of men who got prostate biopsies, a test for cancer, at a Veterans Affairs Medical Center. They included 72 men diagnosed with prostate cancer, 150 with negative biopsies, and compared them to 208 men whose prostate antigen tests, a measure of potential cancer, were normal.

They looked to see which men had taken statins, any statins, for any length of time.

Men with a cumulative dose of more than 19 grams had lower risk of prostate cancer. Those with an average daily dose of more than 40 milligrams were less likely to have an elevated PSA.

Statins May Halve Advanced Prostate Cancer Risk
By Karen Pallarito
HealthDay ReporterMon Apr 18, 7:02 PM ET

MONDAY, April 18 (HealthDay News) -- The statins that many take to lower their cholesterol may be giving men an edge in the fight against prostate cancer, a new study suggests.

Men who used the drugs had about half the risk of advanced prostate cancer and a third of the risk of metastatic or fatal forms of the disease when compared to men who did not use those drugs, the study found.

While these findings are promising, the researchers stressed that more studies are needed to confirm the link and to determine exactly how statins might protect against prostate cancer progression. They presented the results Monday at the American Association for Cancer Research annual meeting in Anaheim, Calif.

Prominent urologists said they are intrigued by the possibilities.

"I think this makes perfect sense," said Dr. Peter T. Scardino, chairman of the Department of Urology at Memorial Sloan-Kettering Cancer Center in New York City and head of the medical center's prostate cancer program.

Around the world, he said, the percent of men at autopsy with cancer cells in the prostate is more or less comparable. "But the risk of dying from prostate cancer differs dramatically: tenfold from country to country," according to the renowned prostate cancer surgeon, who pieces together this evidence in his new book, Dr. Peter Scardino's Prostate Book: The Complete Guide To Overcoming Prostate Cancer, Prostatisis And BPH.

The greatest risk, he said, is in the United States and European countries; less developed counties and Asia have a lower risk. And, he noted, when Asian men migrate to the West, their risk increases.

Dietary fat is believed to be the culprit.

"Cholesterol is the building block of the male hormone testosterone," said Dr. William J. Catalona, director of the Clinical Prostate Cancer Program of Northwestern University's Robert H. Lurie Comprehensive Cancer Center.

Since statins lower blood levels of this fatty substance, there may be less of it available to synthesize testosterone and dihydrotestostrone, he explained. And that may reduce male hormones that stimulate prostate cancer.

The findings deserve further investigation, said Catalona, who pioneered use of the PSA -- prostate-specific antigen -- test to screen for the disease.

This study isn't the first to show the potential cancer-fighting properties of statins. Prior population-based studies suggest those who take statin drugs are at a lower risk of breast, colon and prostate cancers.

In addition, laboratory research suggests statins induce cancer cell death, inhibit the spread of cancer throughout the body and suppress inflammation within cells.

Based on this evidence, lead investigator Elizabeth Platz, an assistant professor in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health, and her colleagues at the National Cancer Institute and Harvard University, followed 34,428 men U.S. men for more than a decade.

The men, who were cancer-free in 1990, were asked to report on their use of cholesterol-lowering drugs every two years. By January 2000, 2,074 men were diagnosed with prostate cancer. Of these, 283 were advanced cases, including 206 metastatic or fatal cancers.

Men taking statins had a 54 percent lower risk of advanced prostate cancer than men who were not using those drugs, the researchers found. Statin users' risk of metastatic or fatal cancer was 34 percent lower than those not on the drugs.

However, statin use was not related to prostate cancer overall or to prostate cancer that was still contained within the prostate, Platz noted.

"Taking the findings together by stage of prostate cancer, we hypothesize that statins do not influence the development of prostate cancer, but that they may influence whether the cancer has the ability to invade and metastasize," she said.

Platz said it would be premature for doctors to prescribe statins to help their male patients avoid advanced prostate cancer, and urologists agree.

"Would I put a patient on statin drug just to reduce his risk of prostate cancer? No," Scardino said.

"I don't think there's enough evidence to recommend statins to prevent death from prostate cancer," added Catalona.
So what can men can do to protect themselves? Reduce fat intake, eat more fruits and vegetables and exercise regularly, doctors say.

"The best way we know is to live a heart-healthy lifestyle," Scardino said.

More information
The Prostate Cancer Foundation has more on prostate cancer symptoms and treatments.

Cholesterol Drugs May Cut Breast Cancer Risk
Mon Apr 26, 6:19 PM ET 

NEW YORK (Reuters Health) - Treatment with cholesterol-lowering drugs, such as Lipitor (news - web sites) and Zocor, does not increase the risk of breast cancer in women past menopause, new research suggests.

On the contrary, the data suggest that long-term use of such drugs, called statins, may actually reduce the risk of breast cancer, according to the findings in the journal Cancer.

"The current study results both provide reassurance concerning the safety of statin use among older women and support the emerging evidence that statins may" protect against breast cancer, the Seattle-based investigators conclude.

There are conflicting reports on the risk of cancer associated with statins, Dr. Denise M. Boudreau from the Center for Health Studies, Group Health Cooperative, and colleagues note in their report. They therefore investigated the association between breast cancer and statin use in a study involving 975 older women with breast cancer and 1007 without the disease.

"We found no evidence of an increased risk of breast carcinoma among statin users," the authors report. In fact, current users who had taken statins for more than 5 years had a 30-percent lower risk of breast cancer compared with non-users.

SOURCE: Cancer, June 1, 2004.

Cholesterol Drugs Seem to Lower Depression Risk

he reason may be that quality of life is improved for patients taking a statin, propose Dr. Susan S. Jick and associates at Boston University School of Medicine in Lexington, Massachusetts.

Their report, in the Archives of Internal Medicine (news - web sites), follows another that concluded statins may reduce the risk of psychological disorders, regardless of their impact on cholesterol levels.

Jick's team identified 458 patients diagnosed with depression between 1991 and 1999, and compared them with 1380 "controls" without any mental illness.

The researchers found that the risk of depression was 30% less for patients who had been prescribed a statin for high cholesterol for up to a year, and 60% less for those prescribed for longer than a year, compared subjects who had high cholesterol but had not been treated.

However, for those taking fibrates or other non-statin lipid-lowering agents, the risk of depression was about the same as for untreated subjects.

"There are some indications that statins are more effective in treating high cholesterol and other cardiovascular risk factors than other lipid-lowering drugs," Jick told Reuters Health. It may be that "the improvement in health conferred by the statins could be responsible for the improved mental health."

Without controlled clinical trials, Jick added, it cannot be concluded that statins have a direct antidepressive effect.

SOURCE: Archives of Internal Medicine, September 8, 2003.

Cholesterol Drugs May Protect Against Cancer: Study
Mon Jun 2, 5:33 PM ET  Add Health - Reuters to My Yahoo!
CHICAGO (Reuters Health) - Cholesterol-lowering drugs called statins that are known to reduce the risk of heart attack and other complications of heart disease may also help prevent cancer, according to new research presented here on Sunday.

In a study comparing more than 3,000 cancer patients with more than 16,000 people who did not have cancer, the overall risk of cancer was 20 percent lower in people who took statins than in those who did not take the drugs. All of the participants were receiving at least one medication for cardiovascular disease.

Importantly, lead investigator Dr. Matthijs Graaf of the Academic Medical Center at the University of Amsterdam in the Netherlands said, only people who took statins for more than four years had a significant cancer risk reduction.

"People who used statins for less than four years did not have a significant risk reduction," Graaf said. The risk of cancer was 36 percent lower in people who took the cholesterol-lowering drugs for at least four years than in people who did not take the drugs.

The findings were presented at a press briefing during the 39th Annual Meeting of the American Society of Clinical Oncology (news - web sites).

Similarly, only statin users of more than 1,350 "defined daily doses" of statins had a significant risk reduction of 40 percent. A defined daily dose is an estimate of the amount of drug that is required for the daily treatment of an adult patient. Those that used less than this specific daily amount did not lower their cancer risk appreciably.

In the study, the researchers took into account several factors that could have affected the results, including diabetes, medical history and the use of several other types of medications. However, they were unable to take into account lifestyle factors, such as smoking.

Cancer risk returned to normal within six months of halting statin treatment.

The majority of statin users, about 80 percent, were taking simvastatin (Zocor) and since the effect of the different statins is not equal, "the results of this study may not be generalized to the use of other statins," Graaf said.

Graaf emphasized that more studies are needed and that, for now, it is not advisable that people start taking statins solely as a means of decreasing their risk of cancer.

Test May Miss Cholesterol Drug-Linked Muscle Damage
Fri Sep 20, 5:40 PM ET  By Alicia Ault
WASHINGTON (Reuters Health) - Some patients who complain of muscle aches and fatigue when taking cholesterol-lowering statin drugs may be having a reaction to the therapy despite tests that find no sign of muscle damage, a researcher said here Friday.
Statin drugs are the most widely prescribed medication in the world, and are taken by 15 million Americans to lower their cholesterol, said Dr. Paul S. Phillips, a cardiologist at Scripps Mercy Hospital in San Diego, California. Phillips is studying patients in his practice to see if they have muscle damage that can't be detected by current tests.
All statins have the potential to cause muscle damage, which can lead to a fatal condition called rhabdomyolysis, in which the muscle completely breaks down. Bayer's statin drug Baycol was taken off the US market in August 2001, after the Food and Drug Administration ( news - web sites) (FDA) received at least 52 reports that people taking Baycol had died of rhabdomyolysis. Another 50 have since died, Phillips said.
He said many of his patients complain of severe muscle aches and fatigue while taking statins, even though they show no signs of muscle damage when their blood is tested for a key enzyme called creatine kinase. High levels indicate trouble. The American Heart Association ( news - web sites) and the American College of Cardiology have recommended that patients be taken off statins if their creatine kinase levels are 10 times normal.
Phillips decided to further study his patients with normal creatine kinase levels. He took samples of their muscle tissue while they were taking statins and also during an 8-week period when they were taken off the drugs.
In a paper in the October 1st issue of the Annals of Internal Medicine, he will report that of the first four people studied, all had muscle tissue abnormalities that are rarely seen. These four patients also were very weak in stair-stepping and hip adductor strength tests.
When the patients went off statins, they felt better, they were stronger and their tissue samples looked normal again, Phillips said.
He is testing more patients and gathering more data, but said he thinks that the currently recommended muscle enzyme test may not detect muscle damage in some people who take statins.
Phillips said he could not estimate how many people might be at risk. "I suspect some are more vulnerable than others," he said, but could not put a finger on which ones yet.
In the meantime, he said he is not even considering taking his patients off the potentially life-saving drugs. "I can't emphasize enough how important statin therapy is in the care of my patients," Phillips said.
In his practice, he is conducting muscle biopsies on people who need statins the most and are having the greatest muscle pain. If they must be on statins, the patients are given dietary changes to try to help minimize the side effects.
Phillips has found that switching the most-affected patients to other cholesterol-lowering drugs has not eliminated muscle aches, meaning there could be something significant about these patients' biology.
He has started a Web site,, to report updates of his findings, and to seek input from statin-takers who are having muscle aches.

Another Statins Benefit Found may lower ldl
Mon Aug 26, 7:06 PM ET
By Serena Gordon
HealthScoutNews Reporter
MONDAY, Aug. 26 (HealthScoutNews) -- Statins are well known for their ability to lower cholesterol levels, but they also seem to be effective at quickly reducing another risk for a heart attack: inflammation.

A new study finds that the drug simvastatin significantly lowered LDL -- the "bad" cholesterol -- as well as levels of highly sensitive C-reactive protein (hsCRP) in as little as two weeks. Elevated levels of hsCRP indicate inflammation and a higher-than-normal risk for heart attack.
The research is scheduled to appear in the Sept. 17 issue of Circulation: Journal of the American Heart Association ( news - web sites).
"This study was really meant to answer one question: How quickly does hsCRP change after statins are introduced?" says the study's lead author, Dr. Robert H. Eckel, a professor of medicine, physiology, and biophysics at the University of Colorado Health Sciences Center. "And the answer is by day 14."
"So, maybe quickly giving a statin could reduce hsCRP and improve the outcome for heart disease patients," says Eckel, adding that more study needs to be done to address that possibility.
Heart disease remains the leading cause of death in the United States, claiming nearly 1 million lives a year, according to the American Heart Association. More than 61 million Americans have some form of cardiovascular disease.
Forty people between the ages of 25 and 75 volunteered for Eckel's study. All had high cholesterol, but no known heart disease. The researchers randomly assigned each participant to one of two groups. One group took the statin drug for 14 days and then a placebo for 14 days, while the other group started with the placebo and finished with the statin medication.
By the seventh day of treatment with the statin, both groups experienced a 56 milligrams-per-deciliter (mg/dl) drop in LDL cholesterol. At the end of two weeks on the statin, LDL cholesterol dropped another 8 mg/dl in both groups.
HsCRP fell to 1.6 milligrams per liter (mg/L) after two weeks on the statin medication from a high of 2.55 mg/L.
Eckel points out that though only one type of statin was tested, other statins would likely have similar effects.
"This study shows a very early effect on hsCRP from statins," says Dr. Carl Lavie, a cardiologist with the Ochsner Clinic Foundation in New Orleans. "It may add to the urgency of starting statin therapy in high-risk patients."
Until further study is completed, Eckel says experts are not recommending any changes in clinical care.
There are other ways to reduce levels of C-reactive protein, including losing weight and quitting smoking, according to Eckel and Lavie. Eckel says some diabetes medications and triglyceride-lowering drugs can also help reduce hsCRP. Lavie recommends cardiac rehabilitation and exercise for heart disease patients, along with a diet high in omega-3 fatty acids (including many types of seafood) to lower hsCRP levels.

Statins Found Safer and Effective

ource: American Diabetes Association
Publication date: 2002-07-09

Even Those With Low Cholesterol Benefit
By Sally Squires
Washington Post Staff Writer
Tuesday, July 9, 2002; Page HE01
Two new reports show that the cholesterol-lowering drugs known as statins are both safer and more effective at reducing deaths from heart attack and stroke than previously thought, findings that are likely to expand the use of these already widely prescribed medications.
British researchers reported Saturday that simvastatin (marketed in the United States as Zocor) reduced heart attacks, stroke and the need for invasive heart procedures, such as angioplasty, by 25 percent. Like previous research, the study also found that deaths from all causes were significantly cut by statin use. But where the British study of more than 20,000 people breaks new ground is in demonstrating a significant reduction in mortality among high-risk people who have normal or low blood cholesterol levels.
"It's a blockbuster study that shows statins bring benefit to higher-risk patients and to groups who might not have been considered candidates for therapy," says Sidney Smith, chief science officer for the American Heart Association.
That, in turn, is likely to change "the rule book on statin prescribing," notes Richard Horton, editor of The Lancet, which published the report, known as the Heart Protection Study. Experts say the British findings could make statins as routine as aspirin for high-risk people -- those who have diabetes, have had a heart attack or stroke or undergone angioplasty or bypass surgery -- even if they have normal or even low levels of the most damaging form of cholesterol, low-density lipoprotein (LDL).
The findings "are the most important and far-reaching results for the treatment and prevention of heart disease and stroke that we have seen in a generation," Horton says.
Publication of the Heart Protection Study comes just a week after a joint committee of the American Heart Association, the American College of Cardiology and the federal government's National Heart, Lung, and Blood Institute (NHLBI) concluded that the five statin drugs on the market are both safe and effective for the majority of patients. The committee was formed last year to review statins after the voluntary withdrawal from the market of Baycol -- at the time one of the most widely prescribed statins in the United States.
"The bottom line is that when statins are given properly and monitored appropriately, they can do a tremendous amount to reduce cardiac risk in our patients," said Richard C. Pasternak, director of preventive cardiology at Massachusetts General Hospital in Boston and chair of the committee that wrote the review.
Since 1987, when the Food and Drug Administration approved the first statin drug -- lovostatin -- the market for this group of cholesterol-lowering drugs has grown widely. The NHLBI estimates that 36 million people in the United States are candidates for statins. In 2000, two statins -- atorvastatin and simvastatin -- ranked second and fourth among the top 10 prescription drug sales in the United States.
Despite their popularity, the new report notes that their potential use "has not been fully realized because many patients at heightened risk are not being treated with these drugs."
The reluctance to use statins is partly fueled by cost and partly by safety concerns.
"There's still a lot of distrust about taking drugs," says Margo Denke, professor of medicine at the University of Texas Southwestern Medical School in Dallas and a member of an NHLBI committee that in 2001 set guidelines for cholesterol treatment. "A lot of people say to me, 'Let me first try losing weight.' But it's very hard to be disciplined enough to stick with a weight loss program."
And once someone has been identified at risk, "it's important to bite the bullet and take the statins," Denke says. "Besides, maybe paying for the drug will get you to get your rear end out there and move and do something about losing weight." (Statins cost about $50 to $115 per month, depending on the dose. Health insurance will often cover part of the cost, but many people pay a co-payment of at least $15 per 30-day prescription.)
Behavioral changes -- giving up smoking, improving diet, daily exercise, achieving a healthy body weight -- remain the cornerstone of heart disease prevention, even for those taking statins.
Cholesterol-lowering drugs "are meant to be an adjunct to lifestyle changes such as diet and exercise," Smith says. "I am very concerned by patients and a society that turns rapidly to medications without first understanding that changing lifestyle has to be the foundation of prevention."
What the latest research demonstrates is the safety and effectiveness of these medications for a wider range of patients. "Should we rethink statin use?" asks David Gordon, special assistant for clinical studies at the NHLBI's division of heart and vascular disease. "Current recommendations are to go for a goal of an LDL less than 100 milligrams." The newest findings suggest, he says, that regardless of LDL levels, statins ought to be used as part of the "routine" prevention in people with known heart disease or in those with a very high risk of coronary disease.
That's because the five statins that remain on the market received a clean bill of health from the clinical guidelines committee, whose findings appear in the latest issue of the Journal of the American College of Cardiology ( The problem of kidney failure, which sidelined Baycol, occurs in only about one in every million users of other statins, the report found.
Even with Baycol, nearly all the 31 deaths linked to its use occurred in frail people, 80 years and older, who had multiple health problems. And the large-scale British study showed no deaths from kidney failure.
As Gordon notes, "the average person who takes [statins] probably has very little chance of getting" kidney failure.
Even so, experts urge statin users to notify their doctors immediately if they experience muscle pain or darkened urine -- signs of muscle breakdown that could lead to kidney failure.
While statins "are safe drugs, as safe as aspirin," says C. Noel Bairey-Merz, a member of the committee that drafted the clinical guidelines, "there is no such thing as a free lunch."•
Publication date: 2002-07-09
© 2002, YellowBrix, Inc.