Tag Archives: Statin

Diabetes Management: Tight Cholesterol, BP Control Does Little Good for Diabetics

Lower isn’t always better in diabetes management. In fact, pushing too hard may not help, and may actually hurt in some cases. This has been proved, once again, by the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, results released last week reveal. Indeed, the new lipid and blood pressure results round out the negative portrait of aggressive risk factor management in diabetes patients.

(ACCORD is one of the largest studies ever conducted in adults with type 2 diabetes who were at especially high risk of cardiovascular events, such as heart attacks, stroke, or death from cardiovascular disease.  The multicenter clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure, and treatment of multiple blood lipids. The lipids targeted for intensive treatment were high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol. Read the Questions & Answers about the ACCORD Trial here.)

According to received wisdom, intensive blood pressure and blood fat management could drive down diabetics’ higher risks of heart problems. But results from the ACCORD trial prove that when it comes to traditional measurements of heart disease risk, a blood pressure target of 120 mm Hg rather than the general population standard of 140 did not reduce nonfatal heart attacks, nonfatal strokes or death from cardiovascular causes.

Likewise, adding the cholesterol-busting drug fenofibrate to standard statin therapy did not reduce the chances of major adverse cardiovascular events. Indeed, tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery, has raised concerns about the ramifications of recommending costly medications that don’t confer real benefits to patients. (See my post ‘Increased Use of Fibrates in US Could Be A Triumph Of Marketing Over Medicine’ here.)

Both studies ‒ part of the complex ACCORD trial ‒ were presented at the American College of Cardiology meeting in Atlanta, Ga. and released simultaneously online in the New England Journal of Medicine.

[A third part of this research ‒ one which examined intensive lowering of blood sugar to see if this had a positive effect ‒ was prematurely halted in 2008 because it turned out that patients receiving this approach actually had an increased, instead of decreased, risk of death. (See a related post ‘Aggressive Diabetes Therapy May Raise Death Risk’ here.)]

As for the newly released findings, the lipid arm of ACCORD included 5,518 patients with high risk of heart problems because of cardiovascular disease or at least two risk factors. LDL, or bad, cholesterol levels had to be between 60 and 180 mg/dL; HDL, or good cholesterol, levels had to be under 50 mg/dL or 55 mg/dL for women and blacks; and triglycerides had to be under 750 mg/dL if the patients were not on any therapy, or 400 mg/dL otherwise. Patients either received fenofibrate or a placebo in addition to statins.

What the researchers found was that lipid and triglyceride levels responded as expected. Despite this, however, the patients appeared to receive no benefit when it came to major heart problems such as heart failure, stroke and nonfatal heart attacks.

Meanwhile, the  blood pressure portion of ACCORD compared a strategy of keeping systolic blood pressure under 120 mm Hg to one of under 140 mm Hg in 4,733 diabetes patients with high risk of cardiovascular events because of clinical or subclinical heart disease or at least two risk factors. In this trial, treatment effectively lowered blood pressure. But again, there was no impact on aspects of patient health including death risk, death related to heart problems and nonfatal heart attacks.

ABC News reported that the U.S. Food and Drug Administration will conduct a full review of findings from the ACCORD study. An FDA spokesperson said the agency planned to include a review of the labeling and indications for fenofibric acid (Trilipix) ‒ even though the trial used fenobrate (TriCor). Asked about the timing of the announcement, the spokesperson said the FDA was attempting to be more proactive.

Both Trilipix and TriCor are marketed by Abbott, and Trilipix is “the active metabolite of TriCor,” according to Dr. Marshall Elam of the Memphis VA Medical Center. Elam, who was involved in the design of the lipid treatment arm of ACCORD said that “neither TriCor nor Trilipix has a label indication for cardiovascular disease.”

In a statement released after the ACCORD results were reported, but before the FDA said it would conduct a review of the ACCORD findings, Abbott said the data from the ACCORD Lipid trial “supports the appropriate patient type and current treatment guidelines for fibrates. The top-line results of the study were widely expected, given that two-thirds of patients in the trial would not be recommended for fibrate therapy under current guidelines.”

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Diabetes: Increased Use of Fibrates in US Could Be A Triumph Of ‘Marketing Over Medicine’

U.S. prescriptions for cholesterol-lowering medications predating statins have increased steadily despite uncertain benefit, suggesting that aggressive marketing has trumped scientific evidence.

These drugs, called fibrates, modestly reduce blood levels of artery-clogging bad cholesterol, raise good cholesterol and are most effective at lowering levels of other damaging blood fats called triglycerides, although the overall picture from clinical trials remains confusing.

Fibrates include gemfibrozil (Lopid), which got the regulatory nod in 1981; fenofibrate (TriCor, Triglide), approved in 2007, and the closely related drug fenofibric acid (TriLipix, Fibricor), which entered the U.S. pharmaceutical marketplace in December 2008. In 2009, fenofibrate and fenofibric acid together accounted for almost 74 percent of the U.S. market share of fibrates.

According to Dr. Cam Patterson, cardiology chief and physician-in-chief of the Center for Heart and Vascular Care at the University of North Carolina, Chapel Hill, “Statins are the only cholesterol-lowering drugs that have been shown conclusively to save lives. Fibrates may be an option as add-on therapy, but there is no compelling case to use them as first-line therapy” for patients with elevated cholesterol, he warns.

Patterson feels the substantial increase in fibrate use demonstrated “unfortunate tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery” and expressed concern about the ramifications of “recommending costly medications that don’t confer real benefits to our patients. We’ve been burned before.”

“The use of fibrates in America is very troubling,” says Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation. Describing the increasing use of fibrates as an expensive failure to educate doctors and regulators, he notes that fibrates are among medications advertised directly to consumers. “This is a classical example of marketing triumphing over science,” he feels.

Dr. James H. Stein, director of preventive cardiology at the University of Wisconsin-Madison School of Medicine and Public Health, says most people don’t realize the influence of marketing on health care. Pointing out that negative studies about fibrates have been “spun to focus on the possible benefits”, he cautions that fenofibrate is associated with significant side effects, including “increased creatinine, which might indicate kidney dysfunction; gallstones, and more serious complications like pancreatitis, blood clots, and pulmonary embolism.”

In the past five years, two major studies have found fenofibrate failed to reduce heart disease risks among diabetic men and women. Last year, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which involved 10,000 patients with diabetes, found that those who took both simvastatin and fenofibrate suffered about as many heart attacks, strokes and deaths as diabetic patients treated with simvastatin alone.

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which involved nearly 10,000 patients and has reported results since 2005, found that fenofibrate failed to decrease cardiovascular deaths more than a placebo.

Yet a new study published in the current issue of the Journal of the American Medical Association found that U.S. prescriptions for fibrates grew from 336 per 100,000 people in January 2002, to 730 per 100,000 people in December 2009. That’s a 117.1 percent hike. At the same time, Canadian prescriptions for fibrates held nearly steady, at 402 per 100,000 in early 2002 and 474 per 100,000 in late 2009.

The increase in fibrate prescriptions, driven by a 200 percent jump in the use of fenofibrate, has outpaced the growth of statins. But, to keep things in perspective: statins, which are among the most commonly prescribed medications, remain blockbuster drugs that dominate lipid-lowering treatment, with fibrates accounting for just 9.4 percent of the U.S. lipid-lowering market in 2009.

Based on a news report in ABC News

All Diabetics Should Take Statins, Say Experts

The European Association for the Study of Diabetes (EASD) has recommended that all people suffering from diabetes should be taking statins, as research showed that the evidence for their effectiveness in reducing cardiovascular risk in diabetics, and even people without diabetes, is incontrovertible.

Professor John Betteridge, of University College London Medical School, pointed out at the EASD annual meeting in September 2010 that all people with diabetes should be taking statins to reduce their chances of having a heart attack or stroke, although he also warned that they should avoid any drug interactions with other medications being taken.

Betteridge has analysed a number of studies into the use of statins, such as the CollaborativeAtoRvastatin Diabetes Study (CARDS), funded by Diabetes UK, the Department of Health and Pfizer, which examined their benefits in people with type 2 diabetes who did not already have evidence ofcardiovascular disease .

In the CARDS study, atorvastatin 10mg/day was shown to reduce major cardiovascular events by 37 per cent and strokes by 48 per cent, reinforcing guidelines issued by the Joint British Society (JBS) regarding targets for low-density lipoprotein cholesterol in this high-risk group.

Betteridge argues that statins are safe if taken appropriately and drug interactions avoided, as they can lead to serious side effects, especially when patients are on a variety of drug treatments. Statins should also not be used by pregnant women at least six weeks before conception.

He realises that statins don’t always get a good press, and that many diabetics will be wary of this advice, but he points out that the evidence shows them to be highly effective in preventing major vascular events in patients with diabetes.

However, the idea of taking statins to offset the effects of junk food has been criticised by diabetes experts. New research had recommended that fast food outlets should give out free statin pills as a way of combating the impact of unhealthy food, as they can reduce the levels of bad cholesterol in the blood, which is why they are normally prescribed to decrease the risk of cardiovascular disease.

There are now worries that using statins could encourage people to lead unhealthier lives, eat more fast food and therefore increase the risk of developing type 2 diabetes. Although studies have found that a single, cheap statin pill could offset the increased risk to the heart caused by the fat in a cheeseburger and a small milkshake, there are concerns that it is both irresponsible and dangerous to promote their use as a quick fix to counteract the effects of an unhealthy diet.

Zoe Harrison, Care Advisor at the charity Diabetes UK, said Statins can reduce the risk of cardiovascular disease by lowering the bad cholesterol in our blood which can be raised due to a high-fat diet. However, they don’t prevent all the side effects that result from an excessive intake of fatty food. Statins also have some serious side effects – such as damage to the liver, pancreas and muscles – which is why they should always be prescribed by your doctor who can then closely monitor how you are responding to the medication.

An Overview of Diabetes and Statins

Diabetes and statins have a complex relationship and are the focus of intense patient and healthcare debate. Statins are cholesterol-lowering drugs.

Statins are used in diabetes care due to the knowledge that people with diabetes face a greater likelihood of heart attack and stroke.

When used alongside good blood glucose control and other medication, the case for statins argues that they cut cholesterol levels and lower the risk of a cardiovascular event.

Type 2 diabetes in particular is certainly a disease of the circulatory system, and this argument has some weight.

How can I lower my risk of cardiovascular problems without taking statins?

There are many ways to lower your risk of stroke and cholesterol levels. These include stopping smoking and controlling your blood pressure. Diet and exercise can help to lower raised blood pressure, and a healthy lifestyle can cut cholesterol levels. However, some doctors prescribe statins to help reduce cholesterol levels.

What do statins do for people with diabetes?

Statins slow the action of the liver in manufacturing cholesterol, causing blood cholesterol levels to fall.

Do statins work for people with diabetes?

Statins definitely lower cholesterol, and major studies have shown that the risk of heart attack and stroke plummets amongst people with diabetes taking statins. Results indicate that statins can prevent cardiovascular disease by reducing heart attack and stroke risks.

What are the side effects of statins?

Statins are usually well-tolerated by people with diabetes. Side effects can include:

• Headaches

• Affect on liver function

• Stomach problems such as abdominal pain, constipation, flatulence, diarrhoea and vomiting

• Rashes

• Disorder of the muscles (myopathy)

Shouldn’t all people with diabetes therefore take statins?

Statins are the subject of current and ongoing healthcare debate when it comes to diabetes patients. Further research is in progress to make the wider use of statins in diabetes care more clear.

Often, people under 40 may not benefit from taking a statin.

A statin is also just one part of diabetes care and shouldn’t be used instead of good diet, exercise, smoking and excess drinking avoidance.

Source: diabetes.co.uk

Effectiveness Of Statins Is Called Into Question

As the world’s most-prescribed class of medications, statins indisputably qualify for the commercial distinction of “blockbuster.” At the zenith of their profitability, these medications raked in $26.2 billion a year for their manufacturers.

But in recent months the drugs’ touted medical reputation has come under tough scrutiny.

Statins were initially approved by the US Food and Drug Administration for the prevention of repeat heart attacks and strokes in patients with high cholesterol who had already had a heart attack. And used for that purpose — called “secondary prevention” — the drugs are powerful and effective medications, driving down patients’ risk of another heart attack or stroke by lowering their levels of LDL (or “bad”) cholesterol.

Then physicians came to believe statins could also reduce the risk of a first heart attack in people who have high LDL cholesterol but are nonetheless healthy. This use of statins — called “primary prevention” — has driven the growth in the market for statins over the last decade.

Today, a majority of people who use statins are doing so for primary prevention of heart attacks and strokes. It is this use of statins that has come under recent attack.

“There’s a conspiracy of false hope,” says Harvard Medical School’s Dr. John Abramson, who has cowritten several critiques of statins’ rise, including one published in June in the Archives of Internal Medicine. “The public wants an easy way to prevent heart disease, doctors want to reduce their patients’ risk of heart disease and drug companies want to maximize the number of people taking their pills to boost their sales and profits.”

Heart patients and their physicians are not the only ones to pin their hopes on statins. The drug companies that brought statins to the market have explored the medications’ benefits in prevention or treatment of such conditions as Alzheimer’s disease, rheumatoid arthritis, prostate and breast cancer, kidney disease, macular degeneration and diabetic neuropathy. Although clear proof that statins could forestall or treat any of these diseases might bring in millions of new, paying customers, results have largely been mixed, inconclusive or disappointing.

In an ideal world, debate over the clinical virtues or vices of a drug would be long settled by the time the medication saw a meteoric rise in use. But in a healthcare system that relies on commercial incentives to spur drug development, prescription medications are a product like any other.

The FDA assesses drugs’ safety and effectiveness for specific use; but its judgments are based on preliminary data, most of it generated by a drug company seeking approval for its product. Once the agency approves a drug for marketing, the company that makes it will move quickly and aggressively to expand the universe of patients taking its product.

Sometimes, by the time the deliberate pace of medical research and debate suggests that a drug is not all it’s been cracked up to be, it’s already become a bestseller. Statins, say some who study the relationship between medicine and the drug industry, seem to fit that pattern.

Statins appear to drive down the risk of heart attack or stroke by lowering the levels of fatty deposits circulating in the bloodstream. Research suggests that the drugs dampen inflammatory processes that can prompt deposits of plaque to break away from blood vessel walls and cause sudden blockages of arteries leading to the heart or brain.

And yet, the relationship between cholesterol-lowering and heart disease is not perfectly understood, and the precise role of inflammation in heart disease is also uncertain.

Statins certainly decrease rates of heart attack in people who have clear signs of cardiovascular disease, but it’s not so clear they work that way in people who are healthy. In spite of that uncertainty, statins’ use for primary prevention has skyrocketed.

That’s the issue in the latest round of debate, which spilled onto the pages of the Archives of Internal Medicine in late June: whether statins prevent, safely and at a reasonable cost, the development of cardiovascular disease in people who are still healthy but are considered to be at high risk of a heart attack or stroke.

In the first of three studies published in the Archives last month, medical researchers found that, contrary to widely held belief, statins do not drive down death rates among those who take them to prevent a first heart attack.

A second article cast significant doubt on the influential findings of a 2006 study, called JUPITER, that has driven the expansion of statins’ use by healthy people with elevated blood levels of C-reactive protein, a measure of inflammation. A third article suggested potential ethical, clinical and financial conflicts of interest at work in the execution of the JUPITER study and concluded the widely hailed trial was “flawed” and raises “troubling questions concerning the role of commercial sponsors.”

“Tens of billions of dollars of revenue for the sponsor over the patent life of the drug were at stake in the JUPITER trial, as well as potentially millions of dollars in royalties for the principal investigator,” wrote Dr. Lee Green of the University of Michigan Medical School in an editorial accompanying the trio of studies. “Doubtless, both sponsor and investigative team believe they made their design decisions for the right reasons,” Green added. “But social psychology research provides abundant evidence that we human beings both respond strongly to self-interest incentives and firmly believe that we do not.”

Statins still have ardent admirers, including cardiologist Steven Nissen of the Cleveland Clinic in Ohio. For many patients on a clear collision course with heart disease but not there yet, he said, statins make a difference. And even though recent studies question whether statins reduce heart attack deaths, Nissen added, many patients’ lives are clearly improved by pushing a heart attack further into the future.

The stakes of this debate are big and continuing to grow (see related story, ” Pinning down the side effects of statins”). As many as three-quarters of patients currently taking statins haven’t yet had a stroke or heart attack; they have diabetes or high LDL cholesterol, conditions widely thought to put them at high risk of having one.

Those patients largely joined the ranks of statin consumers after 2001, when the US National Heart, Blood and Lung Institute adopted guidelines on the treatment of patients with high cholesterol.

The guidelines, updated again in 2004, suggested that as many as 36 million Americans should take statins — essentially tripling overnight the potential American market for the drugs. Of the nine experts involved in drafting the cholesterol treatment guidelines, the National Institutes of Health later acknowledged that eight had substantial financial ties to statin makers — links that may have predisposed them to view evidence of statins’ benefit in its most positive light.

Said Abramson, the author of “Overdosed America: The Broken Promise of American Medicine”: The best way to drive down the risk of developing cardiovascular disease in the first place is to exercise regularly, not smoke, drink in moderation and eat a healthy Mediterranean-style diet. But, he added, “this message gets drowned out by the commercial interests” of pharmaceutical companies who stand to benefit from increased sales.

Courtesy: Melissa Healy/LA Times

Should All Adults With Diabetes Take Statins?

One-third fewer people with type 1 or type 2 diabetes would suffer heart attacks or strokes if they took cholesterol-lowering statin drugs. Cardiovascular disease eventually kills two-thirds of people with diabetes notes Colin Baigent of England’s Medical Research Council. High levels of “bad” LDL Cholesterol play a major role.

Statin drugs lower LDL cholesterol. In people without diabetes, the drugs cut the risk of heart attack, stroke, and other cardiovascular diseases. But it hasn’t been clear whether people with diabetes get as much benefit.

They do, claims Baigent’s study. The researchers pooled data from 18,686 people with diabetes enrolled in 14 clinical trials of statins. The result: People with diabetes, whether male or female, get just as much benefit from statins as anyone else. If 1,000 people with diabetes took statins for five years, 42 of them would avoid heart death, heart attack, or coronary revascularization (bypass or stenting).

“We are saying that, after middle age, almost everybody with diabetes is a candidate for statin treatment – and at a large enough dose to give them a substantial reduction in LDL cholesterol,” says Baigent. “That is quite important, because the size of the benefit depends on the size of the cholesterol reduction.”

The American Heart Association says it’s best to have an LDL cholesterol level of less than 100 mg/dL – and calls LDL cholesterol levels of 100 to 129 mg/dL “near optimal/above optimal.”

Baigent and colleagues calculate that for every 39 mg/dL drop in LDL cholesterol, people with diabetes cut their risk of major heart events by one-fifth. An average dose of statins cuts LDL cholesterol by 57 mg/dL, which would lower this risk by one-third.

But not everyone with diabetes has the same heart risk, argues Bernard M.Y. Cheung, professor of clinical pharmacology and therapeutics at the University of Birmingham, England. “If you are crossing the street, you can choose to wear a helmet because it may save your life in case you are knocked by a car. You are relatively safer, although the absolute risk of this is quite low,” argues Cheung. “But if you are riding a motorcycle, the helmet is going to be important because your risk of an accident is much greater.”

Some people with diabetes have a lower heart-disease risk than others. For them, Cheung says, taking statins would be like wearing a helmet to cross the street.
“It was once believed that the mere fact of having diabetes gives a person the same risk of heart attack as a person who had a heart attack before,” Cheung says. “We are now treating people’s diabetes much better than before, and their baseline risk of heart disease is lower than before.”

Cheung says everyone with diabetes should discuss cholesterol-lowering therapy with their doctors, but he does not think doctors should always recommend drug therapy.

However, Baigent disagrees. “Even if a person has a 1% per year risk of a major cardiovascular event, there is still a benefit from statins,” he says. “So for people whose risk increases over time – and after middle age, that is most everybody with diabetes – there is no point in not treating them with statins.”

Thank you Daniel J DeNoon

Two Therapies May Slow Diabetic Retinopathy in Type 2 Diabetes

In high-risk adults with Type 2 diabetes, researchers have found that two therapies may slow the progression of diabetic retinopathy, an eye disease that is the leading cause of vision loss in diabetics.

Intensive blood-sugar control reduced the progression of diabetic retinopathy, compared with standard blood-sugar control, and combination lipid therapy with a fibrate and statin also reduced disease progression, compared with statin therapy alone. However, intensive blood pressure control provided no additional benefit to patients compared with standard blood pressure control.

Results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study, supported by the National Institutes of Health, recently were published in the New England Journal of Medicine and presented at the 70th Scientific Sessions of the American Diabetes Association.

“This is the largest study to date examining the effects of blood sugar, combination lipid therapy, and blood pressure control on the prevention of diabetic retinopathy progression using retinal photographs,” stated Walter Ambrosius, a professor of biostatistical sciences in the Division of Public Health Sciences at Wake Forest University Baptist Medical Center and principal investigator of the ACCORD Eye study’s coordinating center, in a July 23 release.

“Many people with diabetes have microvascular problems, which can result in problems with the kidneys and amputation of toes and feet, and the only place that you can directly observe the microvasculature is in the back of the eyes. What we have seen in the eyes is potentially an indicator of what is happening in other parts of the body.”

“The ACCORD Eye Study clearly indicates that intensive glycemic control and fibrate treatment added to statin therapy separately reduce the progression of diabetic retinopathy,” added Emily Chew, chair of the Eye Study and chief of the Clinical Trials Branch of the Division of Epidemiology and Clinical Applications at the National Eye Institute.

“The main ACCORD findings showed that fibrate treatment added to statin therapy is safe for patients like those involved in the study. However, intensive blood sugar control to near normal glucose levels increased the risk of death and severe low blood sugar, so patients and their doctors must take these potential risks into account when implementing a diabetes treatment plan.”

The ACCORD study was a landmark clinical trial that included 10,251 adults with Type 2 diabetes who were at especially high risk for heart attack, stroke or cardiovascular death. The study evaluated three intensive strategies, compared with standard treatments for lowering cardiovascular risks associated with diabetes.
Michael Johnsen/DrugStore News

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