Doctors wary after cholesterol drug flop

San Luis Obispo Tribune ^ | Mar. 30, 2008 | MARILYNN MARCHIONE

[neverdem]

AP Medical Writer

Full results of a failed trial on Vytorin, a medicine taken by millions of Americans to lower cholesterol, left doctors stunned that the drug did not improve heart disease even though it worked as intended to lower three key risk factors.

Use of Vytorin and a related drug, Zetia, seemed sure to continue to fall after the findings reported Sunday and fresh questions about why drugmakers took nearly two years after the study ended to give results.

"A lot of us thought that there would be some glimmer of benefit," said Dr. Roger Blumenthal, a Johns Hopkins University cardiologist and spokesman for the American Heart Association.

Many doctors were prescribing Vytorin without trying older, proven medications first, as guidelines advise. The key message from the study is "don't do that," Blumenthal said.

Doctors have long focused on lowering LDL or bad cholesterol as a way to prevent heart disease. Statins like Merck & Co.'s Zocor, which recently became available in generic form, do this, as do niacin, fibrates and other medicines.

Vytorin, which came out in 2004, combines Zocor with Schering-Plough Corp.'s Zetia, which came on the market in 2002 and attacks cholesterol in a different way.

The study tested whether Vytorin was better than Zocor alone at limiting plaque buildup in the arteries of 720 people with super high cholesterol because of a gene disorder.

The results show the drug had "no result - zilch. In no subgroup, in no segment, was there any added benefit" in terms of reducing plaque, said Dr. John Kastelein, the Dutch scientist who led the study.

That happened even though Vytorin dramatically lowered LDL, other fats in the blood called triglycerides and a measure of artery inflammation called CRP.

Results were presented at an American College of Cardiology conference in Chicago and published on the Internet by the New England Journal of Medicine.

The journal also published a report showing that Vytorin and Zetia's use soared in the United States amid a $200 million-marketing blitz. In Canada, where advertising drugs to consumers is not allowed, sales were four times lower.

Congress and state officials in New York have been investigating why results were not released for nearly two years after the study ended.

The drug appeared safe in the study, and patients should not discontinue using it or any heart drug without talking with their doctors, heart specialists stressed.

However, doctors prescribing Vytorin in the mistaken belief it always works "should be thinking twice," said Duke University cardiologist Dr. Robert Califf.

He is co-leader of an even more pivotal study of the drug that was expanded to include more patients because early signs suggest it will be harder than anticipated to see if Vytorin is any better than Zocor alone.

Califf himself takes the drug because he cannot tolerate the high dose of statins he otherwise would need.

"It will be 2012 - ten years after the drug was introduced - before we know the answer," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who has no role in the Vytorin studies and has criticized the drugmakers' handling of the one reported Sunday.

Dr. James Stein, director of preventive cardiology at the University of Wisconsin-Madison, said Vytorin "has always been a second- or third-line drug," after trying statins and other recommended medicines first.

Stein believes Zetia and Vytorin are safe and will prove effective, "but the reason we do research us so we don't have to rely on our "beliefs" - we can rely on data."

Merck is based in Whitehouse Station, N.J.; Schering-Plough, in Kenilworth, N.J.

[shankbear]

Just re-read your post. Never mind.

[neverdem]

Can anyone out there make any sense of this article for me?

Although they saw decreases in the values of LDL-cholesterol, triglycerides and C-reactive protein, presumed to be valid biomarkers for coronary artery disease(CAD), also known as atherosclerosis of the coronary arteies, when they added Zetia to patients with a genetic predisposition to abnormally high LDL-cholesterol they didn't find any significant decrease in the inside thickness of carotid arteries, presumably atherosclerotic plaque.

atherosclerosis a common form of arteriosclerosis in which deposits of yellowing plaques (atheromas) containing cholesterol, other lipoid material, and lipophages are formed on the inner walls of large and medium-sized arteries. adj., atherosclerot´ic., adj.

If you have atherosclerosis of the carotid arteries or peripheral vascular disease, most physicians will conclude that you also probably have CAD. They used ultrasound, the same technology from radar that's used for sonograms in pregnancy and echocardiograms to visualize heart function, to measure the inside thickness of the carotid arteries. Adding Zetia didn't seem to help.

[Pete from Shawnee Mission]

There are a number of fibers that bind to bile. The pectin in fruits, like apples; the gum you find in oatmeal, and yes, guar gum.

(Fibers; Cellulose, hemi cellulose, lignan, gums and one more I forgot.)

If you want to lower cholesterol eat avocados. I did it for a month and lowered mine by something like 20% without messing up my system. Statins reduce your ability to create cholesterol, but you need cholesterol for your skin to make vitamin D3, and you need cholesterol to make coenzeme Q10, or at least so I have been told. Take statins, get tired, and your heart is still at risk. (The heart needs CoQ10 to make energy..

[Uri’el-2012]

.I am a taker or Vytorin,...and it drops the cholesterol count for me,...but gives me a problem with sore muscles....

Consider taking Coenzyme Q10 with the statin.

Or replace the Statin with Red Yeast Rice

[neverdem]

Now that is interesting....I am a taker or Vytorin,...and it drops the cholesterol count for me,...but gives me a problem with sore muscles....

Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. With any statin, tell patients to promptly report muscle pain, tenderness, or weakness. Discontinue drug if myopathy is suspected, if creatine phosphokinase (CPK) levels rise markedly, or if the patient has risk factors for rhabdomyolysis.

Tell your doc! Statins can cause myopathy.

[bmwcyle]

Ask your doctor about Lipitor and Welchol.

[PeaceBeWithYou]

Adobe is the problem(resource hog).

Foxit is the solution.

[NonValueAdded]

Strange article. I too wonder if the two Vytorin components taken separately work. We are told that the drug did great at accomplishing its risk factor reduction. Why blame the drug if the problem lies with faulty cause and effect analysis on the disease itself?

[neverdem]

That’s what I suspected. Thanks for the link.

[millerph]

The study showed that Zetia did nothing to improve outcomes. It didn’t show any harm, just no benefit. Enalapril is a blood pressure medication, not cholesterol.

[1066AD]

Interviewer: To what do you attribute your longevity ?

Julia Childs, Chef: Red meat and gin.

[PeaceBeWithYou]

It seems as though the medical profession doesn't know whether it's coming or going with respect to cholesterol.

Some of them do, most of them are pill pushers.

Infection and coronary heart disease
R. W. Ellis - Department of Clinical Bacteriology, University Hospital NHS Trust, Queen Elizabeth Medical Centre, Edgbaston, Birmingham.

A large body of evidence exists that implicates a number of microbial agents in the pathogenesis of coronary heart disease (CHD). This, if proven, may have far-reaching implications for the prevention and treatment of CHD and other atherosclerotic disease.

The histopathology of atherosclerosis and its natural history suggest infectious causation at many points along the progression of disease, particularly with regard to CHD, and a number of pathogens have been the focus of study.

Viral agents implicated include Coxsackie B4 virus, for which tenuous sero-epidemiological associations exist, and the Herpesviridae.

The animal herpesvirus causing Marek's disease in chickens causes atherosclerotic lesions in these animals.

Herpes simplex virus I and II have been found in aortic smooth muscle and produce changes in vitro in smooth muscle that are similar to those seen at the beginning of atherosclerosis and which may also explain some of the features of atherosclerotic complications.

Cytomegalovirus is implicated more strongly sero-epidemiologically by in-vivo detection in atherosclerotic lesions and by its links with post-cardiac transplant vasculopathya syndrome similar to atherosclerosis.

Bacteria have also been shown to have links with CHD. Chlamydia pneumoniae and Helicobacter pylori have both been associated sero-epidemiologically with CHD, and these findings have been consolidated by recent work showing their presence in atherosclerotic lesions in adults. Bacterial infections in general lead to many changes in lipid, thrombic and other acute-phase protein metabolism, and some of these changes occur with both C. pneumoniae and H. pylori infections.

The ubiquity and similar epidemiological features to CHD of all these microbial pathogens make the resolution of the causative issue impossible by retrospective means. All that can be shown at present are a variety of weak and strong links, the significance of which can only be determined by large and perhaps lifetime prospective studies.

Visit the link for links to other articles that support his findings.

[miele man]

bump

[Paulus Invictus]

No, I can’t. I take Zytorin every day and my cholesterol and all lipids are in great shape. My cardiologist swears by the drug. Now what are we to believe?

[PeaceBeWithYou]

A very good friend who knew a lot about medical research told me the studies that linked cholsesterol and hardening of the arteries were not authoratative, the medical profession ran with them anyway.

I concur, the original "cholesterol is bad study" came out of cold war Russia, and was done on captive rabbits. The 2 long term human studies done since were unconclusive(Framington) and contraindicative(Mr. Fit). The diet(Prudent) that resulted has caused more harm than good, IMO.

[Hildy]

I have the same situation as you. My mother had an abnormal HDL number and I do too...My doctors always do a double take and nobody has ever put me on any medications. the bottom line is you can bring your levels down with diet. I wish more people would take care of themselves and rely less on medication.

[Oorang]

I have not been able to find a brand of Red Yeast Rice that was not made in China. Do you know of one? Thanks.

[Always Right]

High cholesterol is over-rated as a problem. As usual the US medical and drug manufacturers are far more worried about altering symptoms then they are about fixing the real problem. Proper diet and exercise is far more healthier than the drugs that get prescribed.

[Grizzled Bear]

All that is needed by most people is a proper balanced diet and exercise. I know some need meds, but not in the numbers being prescribed...

[Always Right]

A very good friend who knew a lot about medical research told me the studies that linked cholsesterol and hardening of the arteries were not authoratative, the medical profession ran with them anyway. He thought it was mostly genetic that many people can eat/ have high cholesterol and never have hardening of the arteries/ heart disease.

And the study that condemned eggs as the evil food was done on powdered eggs not real eggs.