Beta-Blockers, ACE Inhibitors and Statins in the Battle Against Heart Disease or Failure-Part II

Men and women can calculate their 10-year heart attack risk at a NIH Web site- http://health.nih.gov . There is an index, so go to the H for heart attack section. Use the "Risk Assessment Tool" to calculate your heart attack risk level..

(5/7/08)- The FDA issued a "non-approval" letter, stating it needed more data on Merck's cholesterol lowering drug Cordaptive before it could give the okay on the drug. The agency also rejected Cordaptive as a brand name, so the company said it might use the name Tredative in the United States. On the other hand, a European Union advisory panel recommended approval of the drug for sale in Europe.

Merck has claimed that Cordaptive, which is also known as MK-0524A can both lower bad cholesterol levels (LDL) and raise good cholesterol levels (HDL).

The drug combines an extended-release form of B vitamin niacin, with a new agent, laropiprant, to inhibit a niacin side effect called flushing-redness, burning and tingling of the face. Niacin has been used to control cholesterol for decades, and an extended-release version called Niaspan, made by Abbott Laboratories has been on sale for years.

The results of a 24-week study of Cordaptive were reported on at a European cardiology conference in the fall of 2007. In that study researchers found that compared with a placebo, Cordaptive produced an 18% decline in levels of LDL cholesterol and a 20% increase in HDL levels. It also produced a beneficial 26% decline in triglyceride levels.

Laropiprant has drawn warnings from some health experts because of its possible link to blood clots, and because it has not been tested widely enough to be determined that it is safe.

The U.S. Patent Office has issued another preliminary rejection of Pfizer Inc.'s request for the reissue of a patent for its best selling cholesterol-lowering drug Lipitor. Lipitor's patent remains in effect until March 2010, but the company had hoped to have another patent for the drug reissued for another 15 months past that date.

(4/20/08)- Statins and Coronary Heart Disease- A meta-analysis of 9 randomized placebo-controlled studies of 19,569 patients looked at the effects of statins on mortality in elderly patients (aged >65) with documented coronary heart disease (CHD). They found that all-cause mortality was lower in patients treated with statins (15.6% vs 18.7%) with an estimated 22% reduction in relative risk over 5 years. Statins also reduced the risk of mortality from CHD by 30%, the risk of non fatal MI by 26%, the need for revascualrization by 30%, and the risk of stroke by 25%. It was determine that a median of 28 patients would need to be treated to save one patient. The authors concluded: "Statins reduce all-cause mortality in elderly patients and the magnitude of the effect is substantially larger than had been previously estimated. (See: Afilato J., Duque G., Steele R. et al. Statins for secondary prevention in elderly patients. A hierarchical Baysian meta-analysis. J Am Coll Cardiology 2008; 51(1):37-45)

(4/8/08)- AstraZeneca PLC announced that it stopped a clinical study of its blockbuster statin drug Crestor early, because the cholesterol-lowering drug showed clear benefits over a placebo.

The study was designed to determine whether the drug could reduce the risk of major cardiovascular events in patients with no symptoms of pre-existing cardiovascular disease and low cholesterol, but with high levels of a certain protein linked to heart problems.

(2/16/08)- Researchers continue to conclude that aspirin may help reduce the risk of colon cancer, when taken in large doses over a long period of time. Dr. Andrew T. Chan, an assistant professor of medicine at Harvard who led a study of 47,000 men over an 18 year period of time concluded: "The results provide additional proof that a simple drug like aspirin can help prevent colon cancer".

The results of the study that appeared in the January issue of Gastroenterology was not a randomized study, but some other randomized studies came to the same conclusion.

After adjusting for age, smoking, diet, physical activity and other risk factors, the researchers found that men who took more than two standard 325 mg aspirins a week reduced their risk for colon cancer by about 21% compared with those who took less. Men who took 6 to 14 tablets a week reduced their risk by 28%, and those who took more than 14 pills a week had a 70% decreased risk.

The longer the men took aspirin the more they reduced the risk, but taking it for less than five years, or taking the equivalent of less than one and a half pills a week, conferred no advantage. Other non-steroidal anti-inflammatory medications like ibuprofen (Motrin) and naproxen (Aleve gave similar protections, but not acetaminophen (Tylenol).

The negative side effects of taking aspirin range from upset stomach to gastrointestinal bleeding.

(2/1/08)- The cover story of a recent edition of Business Week casts a doubt on the benefits of statin drugs for non-high risk heart patients. In a study of non-high-risk patients, Pfizer Inc.'s Lipitor, for example, reduced the rate of heart attacks in a three-and-one-half year period of time to 2% from 3%. This means that to prevent one heart attack, 100 people had to take Lipitor for more than 3 years.

Pfizer reiterated that statins do reduce the "risk of death from coronary events", and proponents of statins say the impact needs to be calculated over a much longer period of time.

The magazine does concede however that: "If millions of people are taking statins, even the small benefit…would mean thousands of heart attacks are prevented."

Statins, like Lipitor and Zocor reduce the amount of cholesterol produced by the liver. Some studies have shown that statins greatly reduce the risk of heart attack in high-risk patients. They also do reduce the risk of inflammation. The negative side effect of statins is that they do cause muscle pain in some patients and can have negative effects on the liver.

Zetia has a smaller anti-LDL (bad cholesterol level) effect, and little effect on HDL, or inflammation, but since it works in the digestive tract, it potentially has fewer side effects.

Vytorin by combining Zocor (statin drug) and Zetia produces a bigger drop in cholesterol levels than either drug could do if it was working alone, and without a marked increase in side effects.

(1/26/08)- The ramifications of the Vytorin/Zetia controversy that we discussed in our item dated 1/22/08 below continue to swirl and expand, so that now an issue of conflict of interest has now entered into the plot. The Enhance end-point study of Vytorin, which is made as a joint venture between Merck & Co. and Schering-Plough determined that it was no better than the statin drug Zocor (also made by Merck) working alone at reducing arterial plaque.

The issue that initially caused consternation was the delayed release of the results of the study.

On January 15^th, the day after the results of the study was released, the American Heart Association came out with a statement saying that the announced result was too limited to draw conclusions about Vytorin's ability to reduce heart attacks or deaths compared to Zocor alone. The association advised patients to consult with their physicians before discontinuing usage of the drug.

At no time did the association reveal that it receives nearly $2 million a year from the joint venture

Merck and Schering-Plough have suspended all television ads for Vytorin and Zetia, but print ads, defending the drug have been appearing as full page ads in newspapers such as the NY Times and the Wall St. Journal. .

Total U.S. prescriptions written for Vytorin in the week ended January 18^th fell about 9.5% to 359,659 from 397,533 in the week ended January 11^th, according to Verispan, a Yardley, Pa., drug-data firm. Prescriptions for Zetia, which the Merck/Schering-Plough joint venture also markets, fell 12% to 258,619 from 294,405 the week before according to Verispan.

(1/22/08)- The theory that lowering bad cholesterol levels (LDLs) is beneficial has been an accepted fact for decades now. The results of the Enhance clinical trial of Merck and Schering's combined drug Vytorin, and the disappointing results of the Illuminate study for Pfizer's drug torcetrapib (increasing the good HDLs drug) may be bringing into question that whole theory. For more on the abandonment of pursuing its selling of torcetrapib, please see our article dated 12/19/06 below.

The Enhance clinical trial was a 2-year study evaluating whether Merck's statin drug Zocor (80mgs) which when combined with Schering-Plough's Zetia (10mgs) to form the drug Vytorin was more effective in reducing atherosclerosis than was Zocor when taken alone.

The results of the study as released by Merck and Schering-Plough showed that the study failed to meet the primary as well as the secondary end points. As a matter of fact not only did Zetia fail to slow the accumulation of fatty plaque in the arteries, it actually seemed to contribute to plaque formation, although by such a small amount that the finding could have been a result of chance.

Dr.Steven E. Nissen, the chairman of cardiology at the Cleveland Clinic said, "This is as bad a result for the drug as anybody could have feared." Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, Calif said, "The idea that you're just going to lower LDL and people are going to get better, that's too simplistic, much too simplistic."

The Enhance trial covered 720 patients and lasted two years. It was completed in April 2006. In November 2007, the companies announced plans to change the trial's primary measure of effectiveness to "expedite their analysis", but they reversed course last month after a large outcry of criticism about the ethical matter in changing the primary measure of a trial.

Merck and Schering recently began a large study intended to test whether the combination of Zeia and statin drugs actually reduces heart attacks and strokes when compared with statins alone. The study involves doctors at Harvard and Duke Universities and is called Impove-It, but it will not be available until at least 2011.

Because the link between excessive LDL cholesterol levels and cardiovascular disease has been so widely accepted, the FDA generally has not required drug companies to prove that cholesterol medicines actually reduce heart attacks before approval.

They have not had to conduct so-called outcome or event trials beforehand, which are expensive studies that involve thousands of patients and track whether episodes like heart attacks are reduced.

We are reprinting our article on the Enhance study, which was intended to prove the value of Vytorin which appeared in our article Release of Clinical Drug Trial Data

(12/27/07)- Partial results of studies that had been conducted by Merck and Schering-Plough, showed the possibility that Schering-Plough's cholesterol medication Zetia, when combined with statin drugs might cause damage to the liver, and that this risk had not been revealed by the companies. The discovery of the unpublished research adds more fuel to the controversy involved in the failure of Schering and Merck to make a timely disclosure of the results of the Enhance study that we discuss in the items below.

A Schering executive, Dr. Robert J. Spiegel, when queried about the unpublished studies confirmed their existence. Dr. Spiegel went on to explain that Merck and Schering did not consider the studies scientifically important enough to publish the findings.

Before Zetia was approved in 2002, one FDA reviewer said it should not be cleared for use with statins, because the combination had caused liver damage in animals. In the last two years, scattered case reports of severe liver damage in patients taking Zetia in combination with statins have appeared in medical journals.

The label for Zetia contains only mild warnings about the drug's potential for liver damage. Regulators in Australia and Canada have warned since 2005 about the drug's potential to cause hepatitis, pancreatitis and depression. Most of the studies for which Merck and Schering have published results for Zetia covering only 12 weeks, which is not enough time for liver problems to develop in most patients.

The unpublished studies were conducted from 2000 to 2003 according to FDA documents but were not listed on the industry Web sites where campaniles are supposed to register the results of all drug trials that were ongoing after October 2002. When the FDA approved Zetia in 2002 it relied on trials that covered only 3,900 patients and lasted no more than 12 weeks.

The data from those trials indicated that Zetia might be dangerous when it is combined with a statin.

Reversing course once again, Merck & Co., and Schering-Plough announced that they would present the full results of the Enhance study at the American College of Cardiology's conference in Chicago in March 2008. Please see our items on this topic dated 12/19/07 and 12/4/07 below.

The lead researcher for the study, Dr. John P.Kastelein, a cardiologist at the Academic Medical Center, said that he regretted not standing up to the companies when they announced on November 19 that they would announce only limited primary endpoints for the study, and not the full primary endpoints. The study was completed in April 2006.

The Enhance study was intended to determine whether the combination treatment of Schering's Zetia and Merck's Zocor works better than Zocor alone. Vytorin is a combination pill of both Zetia and Zocor. Zetia is not a statin drug. The study was initially designed to measure changes in the thickness of the carotid artery walls after two years of treatment.

That measurement was taken at 6 points-3 different locations- in carotid artery and would serve as the primary endpoint of the study.

(12/19/07)- The House Committee on Energy and Commerce Chairman John D.Dingell (Dem.-Mich.) and Bart Stupak, the chairman of the committee's subcommittee on oversight and investigations sent a letter to Merck and Schering Plough regarding that "we are concerned with the delay in releasing the results of the study (Enhanced)" that we discuss in our item dated 12/4/07 below.

Vytorin accounts for more than 50% of Schering-Plough's earnings per share, and about 20% of Merck's earnings per share. As we note in the item below the companies completed the study in early 2006 of the drug, and announced that they would reveal the results of the study in 2007. On November 16^th they announced that after consulting with an independent panel of clinical biostatistical experts, that they had decided to change the primary endpoint of the ENHANCE trial. It is very unusual to change the endpoint of a study.

(12/4//07)- Nearly two years after the completion of a clinical study of the cholesterol lowering drugs Zetia and Vytorin in combination, the results have still not been published. Even though there are 800,000 prescriptions written each week, at a cost of about $4 billion, the results of the trial, called Enhance are still unknown.

The two drug manufacturers of the drugs recently announced that they would release the results of one of the three original end-points of the study in March 2008 at the American College of Cardiology's conference in Chicago. The results of a larger clinical study of the drugs are not due to be released until at least the year 2010.

The companies originally said that they would measure the thickness of plaque in two arteries. The first artery would be the carotid artery, which runs through the neck and supplies the brain with blood. The second artery would be the femoral, which runs through the hips and supplies blood to the legs. The primary endpoint of the study was supposed to be the amount of plaque at three points in the carotid artery.

The companies announced however that they would announce only the endpoint of the study at the meeting to releasing only the measurement of the thickness at just one point in the carotid artery. At the same time they announced that they do not expect to release any results from the femoral artery study.

Dr. John Kastelein, a Dutch cardiologist who oversaw the study stated that he believed that the trial should still be considered valid.

The Enhance trial was supposed to show that Zetia and Vytorin (simvastatin) when used together would reduce the growth of plaque in blood vessel walls more than if simvastatin were used alone.

Zetitia works differently than does the statin medications such as Prizer's Lipitor or Merck's Zocor. The FDA approved Zetia in 2002 on the basis of trials that showed it could lower LDL, or so-called bad cholesterol, by 15% to 20%. It is the brand name medication for a cholesterol-lowering medication known as ezetimibe.

It can be taken with any of the statin medications. Vytorin is a pill that combines Zetia with simvastatin, the active ingredient in Merck's Zocor medication. Zetia and Vytorin both cost about $3 a day.

Dr. Eric J. Topol, a cardiologist and director of the Scripps Transitional Science Institute in La Jolla, California stated: " There has yet to be a clinical trial to show that ezetimibe improves clinical outcomes."

(1/19/08)- Genzyme Corp., a biotechnology company based in Cambridge, Mass., has agreed to pay at least $325 million to Isis Pharmaceuticals Inc., of Carlsbad, Ca., for the rights to its potentially powerful cholesterol lowering drug, mipomersen, that Isis is developing.

Mipomersen is in the last stage of clinical trials as a treatment for a rare genetic disease that causes people to have astronomical cholesterol levels. There are only about 10,000 people in the world with the most severe form of the disease, which can cause heart attacks even in young children.

The drug lowered levels of cholesterol and other blood lipids more than 40% beyond reductions achieved by statins and other existing drugs alone, according to Isis.

Stanley T. Crooke, the chief executive of Isis, said that because mipomersen is injected once a week, it would be aimed at supplementing statins, not competing with them. "It's not going to replace statins, and we would never dream of replacing statins," he said.

Isis expects to file for FDA approval of the drug next year. If approved, mipomersen would likely come on the market in 2010 or 2011.

(9/19/07)- Why are men more reluctant than women to call for an ambulance when they are having a heart attack? In a recent study that was conducted in Minnesota of 1,263 patients who suffered a heart attack, it was found that only 37% of the men in rural areas called for an ambulance while 49% of the women arrived at the hospital in an ambulance.

As a matter of fact the studies have shown that only about half of the people in the throes of a heart attack call for an ambulance. Even calling your personal physician leads to what often may mean fatal delays.

Up to 5% of patients go into cardiac arrest en route to the hospital. If you are not revived within two minutes of cardiac arrest the odds for survival plummet dramatically.

The results of the Minnesota study were presented by Minneapolis Heart Institute researchers at a meeting of the Society of Academic Emergency Medicine last May. The study concluded that patients from rural areas were treated 6 minutes sooner if they called 911, and patients from urban areas were treated, on average, 18 minutes faster when they called an ambulance.

(6/19/07)- The results of a statistical analysis that was done by the Centers for Disease Control and Prevention in Atlanta determined that the rate of death in the U.S. from heart disease was cut in half between 1980 and 2000. The analysis showed that better medication and a reduction in incidence of some risk factors was the main reason for the improved results.

About 47% of the reduction resulted from medical measures such as drug to reduce cholesterol and blood pressure, land improved medical treatment in general. Another 44% of the reduction in deaths came from lifestyle improvements, such as less smoking, healthier dieting and increased exercise.

Janet Croft of the CDC was the lead researcher for the analysis, the results of which were published in a recent edition of the New England Journal of Medicine.

(5/2/07)- Ranbaxy Pharmaceutical Inc., a wholly owned subsidiary of Ranbaxy Laboratories Ltd. of India announced on April 25^th that it had received approval from the FDA to manufacture and market Pravastatin Sodium Tablets in 10mg, 20mg, 40 mg and 80 mg doses. The company will have 180- day exclusivity to market the 80 mg dosage in the U.S.

The Office of Generic Drugs, of the U.S. FDA has determined that their formulation is the bio-equivalent and, therefore, therapeutically equivalent to the reference listed drug Pravachol.

Pravachol is manufactured by Bristol Myers Squibb, and it had over $1.9 billion in sales last year. The drug is used to try and help prevent coronary events.

(4/11/07)- The U.S. Supreme Court declined to intervene in Ranbaxy Laboratories Ltd's appeal of a lower court ruling upholding Pfizer's patent for Lipitor, the top selling cholesterol lowering drug. Ranbaxy is the Indian generic drug company that sought to make a generic version of the drug.

Although consumers are able to purchase a generic version of Merck &Co.'s cholesterol lowering drug Zocor, a recent ruling by the U.S. Court of Appeals will mean that Pfizer's cholesterol lowering drug Lipitor is safe until 2010 from having a generic version of their drug. Lipitor was the world's best selling drug last year garnering over $14 billion in sales in 2006. Both Zocor and Lipitor are in a category of drugs known as statins.

Even though a generic version of the cholesterol-lowering drug became available in the 3^rd quarter of 2006, it could not prevent Pfizer's marketing machine from continuing to increase sales of Lipitor.

The U.S. Court of Appeals for the Federal Circuit refused to reconsider a lower court August 2 decision that upheld one of Pfizer's Lipitor patent's, while invalidating a 2^nd patent that was due to expire in 2011.

(3/29/07)- AstraZeneca PLC of England and AtheroGenics of Alpharetta, Ga., co-marketers of AGI-1067, a new experimental drug aimed at reducing the buildup of plaque inside arteries announced that the drug did not meet its Phase III trial expectations.

The drug was no more effective in reducing the risk of death in a trial involving 6,127 high-risk patients than was the placebo. The drug was the first of a new class of medications called vascular protections, which work by blocking the inflammatory process in arteriosclerosis. Arteriosclerosis is the buildup of plaque, fat, cholesterol and other substances in the inner lining of an artery.

Patients in the trial all had a history of heart disease and all were being treated with a variety of other heart medications, including cholesterol-lowering statins.

AGI-1067 is a drug with both anti-inflammatory and antioxidant activity. AstraZeneca's Crestor has become one of the leading statin drugs in the battle against heart disease. In October 2006 the company discontinued testing of its stroke treatment drug NXY-059.

(3/11/07)- The FDA has granted approval to Novartis AG, the Swiss drug company to sell its blood-pressure medication Tekturna, which is generically known as aliskiren. This is the first new type of medication for treating high-blood pressure approved in more than a decade.

It was developed in collaboration with Speedel Holding AG, a small Swiss pharmaceutical company that was founded by a former executive of Novartis, Alice Huxley. Novartis had the original rights to develop the drug, but after having run into snags in developing the drug, turned to Speedel for further work on the medication.

After Speedel managed to simplify the drug's chemical synthesis, Novartis bought back the rights to the drug and completed its development. Novartis submitted Tekturna for European Union approval in September 2006. If approved it would be sold under the brand name of Rasilez in Europe.

(3/5/07)- The results of a recent 6 month study of 192 adults with mildly elevated cholesterol levels showed that there is no evidence to support the theory that garlic works any better than a placebo in reducing blood lipid concentrations.

The results of the study appeared in a recent edition of The Archives of Internal Medicine.

Researchers divided the participants into four groups to consume either raw garlic, a powdered garlic supplement called Garlicin, a popular brand of aged powdered garlic called Kyolic 100 or a placebo.

The doses were the equivalent of one four-gram clove of garlic a day, six days a week for six months.

The researchers tested for LDL cholesterol, HDL cholesterol, triglycerides and total cholesterol HDL ratio, but found no statistically or clinically significant difference between garlic users and those who received the placebo. Christopher D. Gardener, who is an assistant professor of medicine at Stanford University, was the lead author of the study.

(2/9/07)- Back in 1975 a study of 8,341 subjects who had suffered heart attacks found that niacin, or vitamin B, was the only treatment among five tested that helped to reduce the risk of a second heart attack. Compared with men on placebos, those on niacin had a 26% reduction in heart attacks and a 27% reduction in strokes. Fifteen years later, the mortality rate among the men on niacin was 11% lower than among those who had received the placebos.

The reason advanced for this difference is the fact that niacin improves the HDL, or good cholesterol level. It is estimated that niacin can improve the HDL level by as much as 35% when taken in high dosages of about 2,000 mgs a day. It also lowers the LDL level, or bad cholesterol level, but not as much as the statin drugs do.

Niacin has also been shown to reduce serum levels of artery-clogging triglycerides as much as 50%. On the down side is that it dilates the blood vessels and causes flushing problems. In rare cases the vitamin can cause liver damage and can impair the body's use of glucose. High doses should be taken only under the strict supervision of a physician.

Researchers at 72 sites in the U.S. and Canada are recruiting 3,300 heart patients for a study led by Dr. B. Greg Brown, professor of medicine at the University of Washington in Seattle which will compares those who take niacin and a statin with those who take only a statin. The National Institutes of Health will finance the study.

Doctors who do recommend niacin for their patients recommend that it be started on small dosages, and also that food be eaten at the same time as taking the pill. A new Merck drug is being tested in Britain to counteract the niacin-induced flushing problem. If it works, the company plans to bundle the drug with its own extended-release niacin and Zocor, its statin drug that came off patent recently.

(12/26/06)- According to the results of research by scientists from the Framingham Heart Study, the new blood tests being administered now are no more accurate at predicting who will get a heart attack than are the old measurements of cholesterol level, blood pressure, and other conventional measurements

These substances included C-reactive protein, or CRP; homocysteine; and BNP, or B-type natriuretic peptide. The difference in accuracy of these new tests was considered so small as to be negligible. "It's a little bit disappointing," said lead author Thomas J. Wang, a Harvard Medical School assistant professor.

The results of the study were published recently in the New England Journal of Medicine. The researchers used frozen blood samples taken from 3,200 healthy Framinghma, Mass., participants in the mid-1990s, and then checked to see who had major heart complications or died over the following decade.

"This really supports the value of focusing on risk-factor reduction, not looking for a magic blood test, "said Richard Stein, director of preventive cardiology at Beth Israel Medical Center in New York

As a follow up to our item about the C-reactive protein (CRP) blood test in this article several weeks ago, the Centers for Disease Control and the American Heart Association have issued guidelines for the usage of this test. The test is not a replacement for traditional cholesterol and blood pressure tests. It should be used for patients whose risk already appears to be high from these other tests.

In the accompanying chart we list some of the risk factors, and the levels to consider for being at risk for a heart attack:

(12/19/06)- Cardiovascular conditions resulted in over 911,000 deaths in America in 2003.according to the American Heart Association. This made it the number one killer and unfortunately what was once a promising drug in the battle against the disease will now have to be discarded. The drug is Pfizer Inc.'s torcetrapib, which the company had expressed the hope would become a billion dollar seller in the next few years.

Torcetrapib works by increasing the good cholesterol level or HDLs. The failure of this drug in its trial study, which was called Illuminate, will result in the company's taking close to a billion dollars to write off. The trial had been scheduled to end in 2009.

Illuminate compared 7,500 patients taking a combination of torcetrapib and Lipitor, Pfizer's best selling statin drug, with a similar number of patients taking only Lipitor. The patients had diabetes or cardiovascular disease, making them higher risk candidates to having heart attacks or strokes.

Not only were there 31 more deaths among the people taking torcetrapib,, but similar discrepancies were seen in the number of patients suffering heart failure and other serious problems. Those patients taking torcetrapib saw a significant increase in their blood pressure levels also.

The question still remains open as to whether or not increasing the good cholesterol levels (HDL) is beneficial in preventing heart problems, or in the case of torcetrapib, is the problem of only this particular drug. AstraZeneca's Crestor increases the good HDL levels as well as reduces the bad LDL levels.

(12/4/06)- Isis Pharmaceuticals, which is based in Carlsbad, California said that preliminary results of the Phase II study of its cholesterol drug ISIS 301012 showed that the drug cut levels of "bad" cholesterol 62% for patients who received the drug over a 3 month period of time.

The results of the study were announced at the American Heart Association's annual meeting in Chicago recently. Patients who took the drug with statins, had 51% lower levels of "bad" cholesterol after 5 weeks than those who took statins alone.

(11/1/06)- How low should your harmful LDL cholesterol level count reach? Two years ago, the National Cholesterol Education Program urged high-risk patients to reduce their LDL levels to below 100 milligrams a deciliter, from the prior recommendation of 130 milligrams. Those who are considered at very high risk were recommended to get their LDL levels to less than 70 milligrams.

A recent study questions whether or not getting the cholesterol count to these lowered levels is effective in preventing heart attacks.

"This paper is not arguing that there is strong evidence against the LDL targets, but rather that there's no evidence for them," said Dr. Rodney A. Hayward, a study author. The study went on to question the methodology in which the clinical trials had been devised and carried out.

The results of this study were published in the October 3^rd issue of Annals of Internal Medicine. Dr. Hayward is director of the Veterans Affairs Center of Health Services Research and Development, and a professor at the University of Michigan Medical School.

Statins have effects other than just lowering cholesterol levels, such as anti-clotting and anti-inflammatory results, that can be deemed harmful to a patient.

(8/30/06)- Merck & Co., the Whitehurst Station , N.J. pharmaceutical company, released the preliminary results of its large study called Medal of Arcoxia, the drug that the company hopes will replace Vioxx, the painkilling medication that it had to withdraw from the market in September, 2004.

Arcoxia is already approved to be sold in 62 countries, and garnered $126 million in sales in the first half of this year. At last count, Merck is faced with over 14,200 lawsuits as a result of Vioxx.

According to Merck, the preliminary results of the Medal study showed that Arcoxia is no more dangerous to the heart than is diclofenac, a prescription drug sold under brand names that include Cataflam and Voltaren. Diclofenac is not popular in this country because of fear that the drug increases liver problems.

Both Arcoxia and diclofenac belonhg to the class of drugs known as non-steroidal anti-inflammation drugs (Nsaids).

The company's statement also indicated some potential worries for Arcoxia, namely increased rates of hypertension and edema that caused some of the Arcoxia patients to drop out of the study.

There were three clinical studies done of a total of 34,700 patients in the Medal study. Patients took the drugs for an average of 17 months, and 10,000 of the patients took them for two years or more. The 17-month period of time is interesting, since many health professionals feel that Vioxx major problem for heart attacks arises after 18 months of usage of the drug.

On average, patients who took Arcoxia were slightly less likely to have a heart attack or other serious cardiovascular problems than those who took diclofenac, according to Merck.

Many health professionals feel that a more accurate measurement for Arcoxia would have been to compare it with naproxen-sold over the counter as Aleve- rather than diclofenac.

Both Arcoxia and diclofenac are Cox-2 inhibitors, as are Vioxx, and Celebrex, the Pfizer painkiller that is still on the market. In announcing the preliminary results Merck stated that it intended to push for FDA approval to sell the drug in this country.

In October 2004, the FDA responded to Merck's application for approval to sell Arcoxia by asking for more information. 

(8/19/06)- The results of a recent study of Pfizer Inc.'s cholesterol-lowering medication Lipitor that was published in the latest edition of the New England Journal of Medicine found that the drug had only modest success in lowering the stroke rate in people with prior strokes.

Although the study showed that Lipitor did have a slight affect in lowering the risk of stroke for patients who had prior strokes, it did increase the risk for those having hemorrhagic strokes. Hemorrhagic or brain strokes are the more devastating type of stroke as opposed to the other type of stroke known as ischemic stroke, which is generally caused by a blood clot, or a mini stroke.

The study looked at 4,731 people who had no known cardiac problems but had experienced at least one stroke within the prior one to six months. Pfizer Inc sponsored the study.

Lipitor is approved for stroke prevention in people who have, or are at high risk for, coronary disease. Among the patients who took Lipitor, 265 or 11.2% suffered another stroke over a five-year period of time. That compared with 311, or 13.1%, or those getting placebo pills that suffered an additional stroke.

55 of the patients who were taking Lipitor suffered hemorrhagic strokes compared to only 33 of the patients taking the placebo who suffered strokes.

One of the study's co-authors, Justin A. Zivin of the University of California, San Diego said; "The (beneficial effect) is about what you get from aspirin. It's not dramatic or earth shattering."

Hemorrhagic strokes are rarer than ischemic strokes, accounting for less than 20% of the 700,000 strokes each year in the U.S., but they carry a much higher risk of long term disability, especially to people who are on blood thinners such as Coumadin.

(7/27/06)- Merck's Zocor, its cholesterol-lowering drug, which lost its patent in the U.S. on June 23 is having an effect on the sale of Pfizer's Lipitor and AstraZeneca's Crestor. It is also leading the other generic drug sellers of simvastatin, the generic name for the drug.

Merck's generic version of the drug captured 49% of new prescriptions in the U.S. for the drug that were written for the last week in June. Teva Pharmaceutical Industries Ltd of Israel captured 32% of the 236,000 new prescriptions for all dosages during the last week of June. Dr. Reddy's Laboratories of India, which makes generic simvastatin under an agreement with Merck gained 14% of the new prescription market for the drug, while Ranbaxy Laboratories Ltd of India, which makes only the highest dosage of the drug gained 3% of the market.

Sales of Lipitor, the most popular version of the statin drugs sold to combat high cholesterol levels saw its percentage of the market for the medication drop to 40% from 42% the week before when the generic version of the drug was not available.

According to data from ImpactRx, a research firm in Mount Laurel, N.J. Zocor and simvastatin sales combined prescriptions exceeded those of Lipitor for the first week in July among primary-care doctors. During the week ended July 7, Zocor and simvastatin accounted for 23% of cholesterol drugs prescribed for newly diagnosed patients or those switching medications, compared with 20% for Lipitor. Just a month earlier, Lipitor claimed 23% of new prescriptions while Zocor accounted for only 16% of the prescriptions.

(7/4/06)- A federal judge has denied a motion from Novartis AG to temporarily block the FDA from approving Teva's and Ranxbary's generic versions of Zocor, and affirmed their 6-month marketing exclusivity. Novartis' generic division Sandoz wanted to market a generic version of the drug, but Judge Royce C. Lamberth of the U.S. District Court for the District of Columbia said the temporary delay would be detrimental to both Teva and Ranxbary. He went on to say that even a temporary delay would be harmful to the public.

Teva won approval to market the pill in 5-, 10-, 20-, and 40-milligram versions, while Ranbaxy won approval to sell the 80-mg version of the drug. Dr. Reddy's Laboratories Ltd, under an agreement with Merck will be the so-called authorized generic maker of the pill and will sell all five dosages.

(6/25/06)- On June 20, 2006 the patent for Merck & Co.'s cholesterol-lowering drug Zocor expired. In a very interesting move, the company has sharply lowered the price of the drug, and is selling it as a branded generic version of simvastatin. By adopting this strategy of selling the generic version of the drug at a sharply lower price, Merck is hurting the generic drug companies Teva Pharmaceuticals USA, a unit of Teva Pharmaceutical Industries Ltd., of Israel and Dr. Reddy's Laboratories Ltd., an Indian generic drug maker.

These two generic drug companies are being hurt by this action since they expected to have the exclusive right to market the generic version of Zocor for the first 6 months after the patent expired. They were the two companies that were the first ones to apply to market the generic version of the drug after the patent expiration. The law dictates that the first applicants who receive the approval of the FDA to market the different dosages of the drug have the right of exclusivity of the 6-month period of time after the patent expires.

This article contains information about other instances of the pharmaceutical companies making "branded" generic versions of their drugs. In selling a branded version of a drug, whose patent has expired, a drug company can thus capture a portion of the sales after the patent's expiration. This in turn is harmful to the generic drug company that expected to have exclusive rights to sell the generic version of the drug for 6 months after the expiration.

It is reasonable to expect that many drug companies will adopt this strategy in the future when the patent expires on one of its drugs.

WellPoint Inc., an Indianopolis health insurer announced that it had entered into an arrangement with Merck to sell branded Zocor, and not competing generic versions, through its mail order pharmacy service. Members of WellPoint will pay $10 for a 30-day supply of branded generic Zocor.

UnitedHealth Group Inc. said that branded generic Zocor would move to the cheapest tier of its drug formulary, making the co-payment for customers cheaper than the generic alternatives.

Making a branded generic version of Zocor is going to have a huge impact on Pfizer's Lipitor, the biggest selling drug in the world, with revenues worldwide of $12 billion last year. On a personal basis, this author's pharmacy benefits manager ExpressScipts notified all members of its plan with the company I work for, that the co-pay for a 90-day supply of Lipitor would be increased from $70 to $140.

Lipitor is now faced with competition from two drugs that lower cholesterol even more than it does. One is Vytorin, which is made by Merck and Schering-Plough, which combines Zocor and Zetia. This combined pill has a different mechanism of action than statins. In addition to lowering the bad cholesterol level, the drug also increases the users good-cholesterol level. This drug had sales of $378 million in the first quarter, which indicates that it is on track to become a blockbuster over a billion dollar seller this year.

The other new challenger to Lipitor is Crestor, a drug from AstraZeneca that is generally considered the most potent of the statin drugs.

Up until now, Zocor has sold for about $3 per pill. Once it is sold as a generic drug, the price probably will go down between 75% to 90%. The falling price will save insurers and patients billions of dollars. It is unknown at this point if employers will benefit to any great amount by this action.

For more on this topic please see our article on "Branded" Prescription Drugs"

(6/12/06)- According to a recent research report that was published in The New England Journal of Medicine ACE inhibitors may cause birth defects if taken by pregnant women in the first three months or pregnancy. It had been previously determined that ACE inhibitors can cause birth defects if taken later on during pregnancy, and drug labels have the warning for pregnant women in the second and third trimester..

Pregnant women and those planning to become pregnant should avoid the drugs, according to the researchers and officials at the FDA. The researchers had studied the medical records of 29,507 infants. The study found 209 infants who had been exposed to the drugs in the first trimester. Of the 209, 18 had birth defects; in half of the 18 cases the heart of the newborn was affected.

Dr. Robert Temple, an associate director of the Center for Drug Evaluation and Research at the FDA, said the 2.7 fold increase in risk was "moderately large", but the agency does not plan to require a "black box" change in ACE inhibitors labeling information as of now. He said that further studies were needed before the warning need be placed on the prescription label.

ACE inhibitors are used to treat high blood pressure. Last year there were about 42 million prescriptions written for the drug. According to Dr. William O. Cooper, a Vanderbilt pediatrician who headed the study team, there were about 2.7 million ACE inhibitor prescriptions written for pregnant women in 2002

All drugs are tested in pregnant animals before they are marketed. It is obviously unethical to test these same drugs in pregnant women, so this risk factor can not be evaluated until after pregnant women have used a drug. With more and more women giving birth at later ages this will become an even more difficult problem for our society.

Some of the better selling ACE inhibitors are, Merck's Vasotec, Pfizer'sl Accupril and Bristol-Myers Squibb's Capoten.

A study published in 2002 found that diuretics were as effective in preventing heart attacks as ACE inhibitors.

(5/26/06)- A study that examined FDA records from the last ten years concluded that about 164,000 emergency defibrillators had been subject to FDA recall or alert notices. This works out to about one out of every five units that were sold during that period of time.

The study's lead author, Dr. William H. Maisel of Beth Israel Deaconess Medical Center in Boston said, "Many failure occurred during life-threatening circumstances." "It does not mean that every one of these people could have been saved, but these are very high risk malfunctions." The study did not address internal defibrillators, which are surgically implanted into the chests of heart patients who are at high risk of cardiac arrest

(3/26/06)- In a study of more than 500 patients who were taking a high dosage of AstraZeneca's statin drug Crestor the volume of plaque was reduced by 7% to 9%. The drug also lowered levels of LDL, or bad cholesterol, by more than 53%, and it raised levels of HDL, or good cholesterol by nearly 15%. The results of the study were presented at the recent meeting of the American College of Cardiology in Atlanta.

The issue remains however as to whether or not the lowering of the plaque level will mean fewer heart attacks and strokes. Artherosclersis, or blockage in arteries, results when a buildup of cholesterol, inflammatory cells, and fibrous tissue called plaques form in an artery wall. If these plaques break off, it cause blockages prevent the blood from flowing properly where needed by critical organs leading to heart attack or stroke.

All the statin drugs lower the level of plaque in arteries, although some do it to a greater extent than the others.

A consumer group, Public Citizen to have Crestor petitioned the FDA last year to ban Crestor as unsafe, but the agency denied the request.

Homocysteine level, an amino acid that many health professionals believed to be as important and dangerous a risk factor for heart disease and stroke was the subject of 3 studies that were reported on recently. It is also an accepted hypothesis that the B vitamins, namely: vitamin B12, vitamin B6, and foliic acid, could protect against high homocysteine levels, which in turn would mean less risk of heart attack or stroke.

The results of the three studies however showed that by decreasing the homocysteine level, the number of patients having cardiovascular problems did not decrease. There are no known harmful affects from taking the B vitamins.

All three studies showed that the vitamin regimens drove patients' homocysteine levels down by nearly one-third. All three studies however did not show any decrease in the amount of cardiovascular problems in the group receiving the vitamin B pills from those who only received a placebo.

"The evidence is clear that this type of vitamin therapy is really not effective in reversing or benefiting advanced vascular disease", said the hypothesis's father, Dr. Kilmer McCully of the V.A, Boston Health Care System in West Roxbury, Mass.

The Canadian Institutes of Health Research sponsored one of the studies. It involved 5,522 men and women 55 or older who had diabetes or had had a heart attack or had documented heart disease. The patients in this study were monitored for five years. The second of the studies involved 3,749 men and women ages 30 to 85 that had recently had a heart attack. It was known as the Norwegian Vitamin Trial, and it lasted for three years and four months.

The third study involved 3,680 stroke patients, some of whom were randomly chosen to take the vitamins.

(3/21/06)- The anticlotting drug Plavix had over $6.2 billion in sales last year for its distributors Sanofi-Aventis SA of France and Bristol-Myers Squibb of New York. The drug has been approved for usage, along with aspirin, after a patient has had a heart attack, but the question has arisen if the drug would be useful in preventing heart attacks in individuals who are at high risk for having one. Plavix was the second most widely sold drug in the world last year, trailing only Pfizer's Lipitor in 2005.

The answer to this question seems to be no, based on the results of a study of 15,000 patients who were deemed to be at high risk for having a heart attack. These individuals were at high risk because they had had a stroke, or a blocked artery in the leg.

The drug, which is also known generically as clopidogrel, was found to be of no help in preventing a heart attack. The Plavix offered no benefit over standard low-dose aspirin therapy, and in fact it significantly increased the risk of internal bleeding. In fact, when combined with aspirin it was determined that there was only a 1-% reduction in the risk of heart attack.

The study, called Charisma, was presented at the annual scientific meeting of the American College of Cardiology in Atlanta. Both aspirin and Plavix inhibit platelets from forming clots. Researchers found that 6.8% of patients with the combination of Plavix and aspirin had either a heart attack or a stroke or died of cardiovascular disease-compared with 7.4% who were on aspirin plus placebo.

Among patients without established cardiovascular disease, the rate of death from cardiovascular causes was 3.9% for those taking Plavix and aspiriin, compared with 2.2% for those taking aspirin alone.

Plavix is approved for patients with a recent heart attack or unstable chest pain, and for people treated with drug eluting stents. Studies have shown that when such patients stop Plavix, even while continuing aspirin, they significantly increase the risk of developing a clot in the stent. 

(1/12/06)- Researchers concluded, after analyzing 26 randomized studies involving more than 73,000 patients, that statin drugs had no effect on cancer risk or cancer deaths. The findings appeared in the recent issue of the Journal of the American Medical Association. The results of the study therefore contradicted the results of a non-randomized study that concluded that statins did have the beneficial effect of lowering the risk of colorectal cancer in people who used statins for at least 5 years.

In a separate study, the results of which appeared in the Journal of the National Cancer Institute, it was determined that the statins drugs had no effect in reducing the risk of colorectal cancer. This study looked at data on more than 132,000 people who enrolled in a cancer-prevention study.

C. Michael White of the University of Connecticut School of Pharmacy led the analysis of the data appearing in the Journal of the American Medical Association.

(12/20/05)- Judge Joseph J. Farnan Jr. of the Federal District Court in Delaware ruled that two critical patents protecting atorvastatin, the active ingredient n Lipitor, are valid. As a result of this ruling Pfizer's patent on Lipitor will hold until June 2011. Ranbaxy Laboratories, the Indian drug company will appeal the ruling. For background information on this case please see our article: Patents and Prescription Drugs -Part II and also Cox-2 Inhibitors and Rheumatoid Arthritis-Part III

(11/16/05)- According to the results of a study, that was published in the October 18 edition of Lancelot, beta-blockers do work to reduce the risk of stroke, but not as well as other medicines, and they are ineffective in preventing heart attacks. Dr. Lars H. Lindolm, the chairman of the department of public health and clinical medicine at Umea University Hospital in Sweden, and the lead author in the study stated: "What has happened is that a drug that was excellent for secondary prevention-that is, in people who suffer from heart disease-has been moved to primary prevention," and is much less effective in that role.

The study examined the results of 13 randomized trials and concluded that the drugs, which have been the first-line treatment for hypertension for at least 25 years, produce a higher risk for stroke when compared with other drugs used for the same purpose. Dr. Lindholm emphasized that the results pertained only to people who had high blood pressure without heart problems.

(10/20/05)- A large federally sponsored study found that the usage of statin drugs is even greater than originally believed. The study, the National Cholesterol Education Program involved more than13,000 adults. It found that use of statin drugs nearly tripled to 9.3% of adults age 20 and over, compared with a similar-size survey taken between 1998 and 1994.

Among men 60 and over, statin use nearly quadrupled to 24.3% from 6.8%, while it jumped to 21.6%, from 8.7% in women that age. The study's lead researcher was Margaret D. Carroll, a researcher at the CDC.

On June 23, 2006 Merck is slated to lose its patent for its statin drug Zocor (simvastatin). The company may try to extend the life of the patent, but some of the prescription benefit managers (PBMs) will be taking steps to get their members to switch to generic versions of the drug as soon as they can.

Express Scripts, said it would drop Lipitor (atorvastatin) from its list of preferred drugs. At the same time it will lower the co-payment cost for those taking the generic version of Zocor. WellPoint Health, the nation's largest health insurer will offer its members a four to six month free supply of the generic version of Zocor. Ivac, a generic drug manufacturer will produce a generic version of Zocor as soon as it can do so legally.

Merck has introduced another anticholesterol drug, Vytorin, which combines Zocor, which decreases the bad LDL, with Zetia, a medicine from Schering-Plough, that is not a statin, but acts to increase the level of the good cholesterol, the HDL.

(9/5/05)- Researchers who studied the records of more than 170,000 heart-attack patients concluded that the risk of death was reduced by about 50% if a statin drug is administered to the patient right away. Gregg Fonarow, a cardiologist at the University of California led the study group that was funded by Genentech Inc., which currently does not make a statin drug. Dr. Fonarow has done research for several companies that make statins.

The results of the study were published in the September issue of the American Journal of Cardiology. Those given statin drugs before hospitalization and within 24 hours after a heart attack had a 54% lower risk of dying in the hospital, compared with those not given the statin drug. According to Dr. Fonarow: "We also found that statins provided additional protection from other heart-attack complications."

(7/12/05)- The National Institute of Health's Heart, Lung and Blood Institute will provide about $22 million in funding for a six-year clinical study to see if raising "good cholesterol" (HDL) with a drug based on the vitamin niacin, while lowering "bad cholesterol" (LDL) with a statin, can prevent more heart disease than the statin alone. Pfizer Inc. is spending more than $600 million on clinical tests of a combination of its drug Lipitor and torcetrapib, an experimental drug that raises HDL levels.

The study is expected to involve 3,300 patients,l about a third of them being women. Prospective candidates for the study must have existing cardiovascular disease and be candidates for drug therapy. The patients will receive either simvastatin, the generic name for Merck's cholesterol lowering drug Zocor (simvastatin) plus Niaspan, an extended-release form of niacin available by prescription from Kos Pharmaceutical Inc. of Cranbury, N.J. Zocor will lose its patent in 2006, so Kos will apply to the FDA to sell the combined pill thereafter.

Kos presently sells Advicor, a combination of Niaspan and lovastatin, a generic form of Merck's statin drug Mevacor, whose patent has already expired. Kos will also contribute about $20 million in unrestricted financing towards the study. The study is expected to begin in about 50 to 60 clinical sites in the U.S. and Canada in November.

(7/6/05)- According to a new analysis of the large "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" (Allhat) which was conducted in 2002, diuretics worked equally as well as or better than newer more expensive drugs. Included in this latter category of drugs are ACE inhibitors and calcium-channel blockers in protecting against heart attacks and offer more protection against congestive heart failure.

The results of the new study were published recently in the latest edition of the Archives of Internal Medicine. The study group was led by Jeffrey Cutler, a senior adviser at the National Hear, Lung and Blood Institute a unit of the National Institute of Health

(7/2/05)-The FDA accepted the recommendation of its advisory panel and approved for immediate sale NitroMed (Lexington, Mass.)drug BiDil for heart failure to Afro-Americans. The drug makes it easier for the heart to pump by relaxing blood vessels. The drug had been rejected in 1997 by the FDA for use in all patients after two clinical trials conducted in veterans hospitals did not show statistical benefit.

It is the first time a drug has been approved by the FDA for one particular race. No one is sure why BiDil works better in blacks than in others. Some scientists theorize it works because it increases the body's level of nitric oxide, and this deficiency is more common in blacks than other races. An estimated 5 million Americans, 750,000 of them black suffer from heart failure.

Schwartz Pharma Manufacturing of Seymour, Ind, is manufacturing the tablets. The tablet is a combination of two generic drugs that are already on the market. These two drugs are hydralazine and isosorbide. NitroMed has not announced yet what price it will charge for the medication.

BiDil was the discovery of Dr. Jay N. Cohn, a cardiologist at the University of Minnesota, who in the 1970's began experimenting with vasodilators, or vessel-widening treatments for desperately ill patients. The FDA denied BiDil's approval in 1997, after determining that Dr. Cohn's results were not statistically significant.

The drug is to be taken three times a day, in addition to the heart failure medication that a patient is already taking.

(6/7/05)- The journal, Circulation, which is published by the American Heart Association had the results of a study that was done under the leadership of Dr. Richard H. Karas of Tufts University that concluded that AstraZeneca's Crestor had higher rates of some serious adverse effects than did some of the other statin drugs.

For the four drugs studied, the absolute rate of adverse events per million prescriptions was low: 28 for Crestor, 13 for Zocor, 3.5 for Pravachol and 4.3 for Lipitor. The authors of the study did not call for the removal of Crestor from the market. The FDA said that it stood by the results of its study announced in March, when it rejected a petition filed a year earlier by Public Citizen which claim the risk from usage of Crestor was too high for muscle and kidney damage.

The FDA concluded that "all the available evidence" showed that Crestor had no greater risk of muscle toxicity or serious kidney damage that the rival statins, Lipitor, Pravachol and Zocor. Each patient should be evaluated individually by his or her own physician to determine which of the statins would be the best choice for that particular patient.

(4/26/05)-Two studies, involving a total of 50,000 participants in which heart-attack patients were given Plavix as well as a clot-busting drug and aspirin as emergency treatment indicate an enhance chance for survival and even prevent the onslaught of a second heart attack.

In the bigger of the two studies, there were 7% fewer deaths in patients given Plavix. In the smaller of the studies there were 20% fewer serious heart "events" after 30 days, including death and a second heart attack. The combined treatment also helped to keep affected arteries open, which improved long-term recovery and survival from a heart attack.

Plavix, known generically as clopidogrel, is co-marketed by Sanofi-Aventis SA of Paris and Bristol-Myers Squibb Co., both of whom were sponsors of both of the studies. Marc Sabatine, a cardiologist at Brigham and Women's Hospital, Boston was the lead researcher in one of the studies where a 300-mg dosage of Plavix was administered, while the other one was a collaboration between researchers at Oxford University in London, and researchers in China where a 75-mg daily dosage of Plavix was administered.

A major new study suggests that all chronic heart patients would benefit from lowering their bad cholesterol level (LDL) to levels below 80. Last summer, the American Heart Association issued updated cholesterol-treatment guidelines suggesting that doctors consider getting the LDL in very high-risk patients to below 70, based on another study showing significant benefits for high-dose versus moderate-dose treatment with statins.

The study involved 10,001, and it was led by John LaRosa, president of State University of New York Downtown Medical Center, Brooklyn. Pfizer sponsored the study that involved the administration of its 80-mg Lipitor compared to its 10-mg version of the same drug. The result of a comparison study of Prizer's Lipitor and Merck's Zocor is expected shortly.

The average adult in the U.S. has an LDL of about 127, according to the American Heart Association. The new study showed a small increased risk of liver inflammation at the higher dose. In the study, 60mg patients reached an average LDL of 77, compared with 101 for those on the 10-mg version of Lipitor At the start of the study the average patient had an LDL reading of 98. After 4.9 years, 10.9% of the patients in the 10-mgs group and 8.7% of patients at 80-mgs had suffered a major event such as a heart attack, stroke or death from heart disease.

(3/5/05)- The American Heart Association has endorsed heart scans as another tool in evaluating a person's risk of having a heart attack. It can be used along with other medical evidence in determining how aggressively a person should be treated to prevent a heart attack. The test typically costs between $250 to $400 and is available in two different types of technologies: electronic beam technology (EBT) or fast computerized tomography scans.

The EBT is the preferred approach because it is more accurate and exposes patients to significantly less radiation than the computed tomograpghy, or CT scans. The tests show the calcium deposits in the patients' arteries. A high measure of calcium increases a patient's risk of having a heart attack.

Steven Nissen, a cardiologist at the Cleveland Clinic stated that the test for C-reactive protein is a more accurate predictor of a patient's heat attack risk. That test which costs as little as $8, which when added to other data provides plenty of information about the patient in evaluating the risk according to Dr. Nissen.

(1/15/05)-A FDA advisory panel voted 20-3 against allowing Merck's application for its cholesterol-lowering drug Mevacor to be sold without a prescription as an over-the-counter medication. A spokesman for Merck and Johnson & Johnson, who had joined Merck in the application, said that they would continue to try and gain approval to sell the drug as an over-the-counter medication. The FDA typically adheres to the recommendations of its advisory panels.

An advisory panel had previously denied similar applications in 2000 to sell statin drugs over-the-counter from Merck for Mevacor and Bristol-Myers for Pravachol. It is estimated that there are over 39 million Americans who are in the moderate risk category because of their cholesterol levels, who might benefit from taking statin medications.

The panel concluded that medical management is required for patients taking statin medications. The patent for Mevacor has already expired, but Merck's statin medication Zocor first goes off patent next year. If a brand name drug company produces a patented drug as an over-the-counter medication, it can gain at least 6 months of exclusivity for its product. Pfizer's Lipitor is the number one selling statin drug with over $9 billion in sales in 2004. Merck's Zocor is the number 2 seller in this market and Bristol's Pravachol is number 3.

One of the voting members of the panel, Dr. Bolsey Barnes, a Washington physician said, "A healthy lifestyle, low-fat diet and exercise may achieve the same result of O.T.C. statins,".

(1/14/05)- A study involving women ages 50 to 79 conducted over a long period of time concluded that the women who took calcium channel blockers in combination with diuretics had a higher death rate than women who were on a combination of beta blockers or ACE inhibitors and diuretics. The researchers in the study followed the women for an average of nearly 6 years. The U.S. government sponsored the study.

Calcium channel blockers relax blood vessels and reduce the heart's workload by affecting the movement of calcium into cells. Diuretics rid te body of excess sodium and water. Sylvia Wassertheil-Smoller, a researcher at Albert Einstein College of Medicine was the study's lead author. The number of heart related deaths was small: 31 out of 1,223 women taking the calcium channel blocker combination had fatal heart attacks versus 18 out of 1,380 on the beta blocker combination and 17 out of 1,413 on the ACE inhibitor combination had fatal heart attacks.

The women involved in the study had hypertension but no history of cardiovascular disease.

(11/18/04 )-A clinical trial involving about 10,000 patients with acute coronary syndrome will compare the effects of Vytorin and Zocor. Vytorin is a cholesterol lowering medication from a joint venture between Merck and Schering-Plough. Zocor is a cholesterol-lowering statin drug from Merck. In the case of Vytorin, it is hoped that a combined pill from Merck and Schering will both lower the level of bad cholesterol (Zocor from Merck) and increase the level of good cholesterol (Zetia from Schering).

The FDA approved the statin drug Vytorin in July for the treatment of high LDL. The purpose of the trial is to assess whether Vytorin is more effective in reducing mortality and morbidity in heart patients versus Zocor alone by dramatically lowering harmful cholesterol levels though dual inhibition.

The results of a study of increased dosage of Zocor indicated that increased dosage of the drug to 80 mgs did not benefit patients who had previously had heart attacks. In fact in did slightly increase the risk of muscle-related complications. Zocor is the second best selling of the 6 statin drugs now on the market. Lipitor is the biggest seller in this group.

Merck, the manufacturer of the drug, paid for the experiment, which included 4,497 patients. Dr James A de Lemons, a cardiologist at the University of Texas Southwestern Medical Center was the principal author for the study. One group of 2,265 patients was given 40-mgs dosages of Zocor for 30 days and then the dosage was increased to 80-mgs. A second group of 2,232 patients took placebos for four months and then was given 20-mgs doses of Zocor for the balance of the experiment. The two groups were followed for up to a period of 2 years.

In a similar experiment involving Lipitor the increased dosage of that drug to 80-mgs did not result in muscle-related complications. The 40-mg dosage of Zocor did not result in any increase risk of muscle-related complications.

The FDA has granted approval to Pfizer Inc. to advertise and include on the label for Lipitor that it cuts the risk of heart attacks, angina and the need for surgery or angioplasty to open clogged arteries feeding the heart. Up until now the drug could only be marketed for its ability to lower cholesterol levels. Zocor from Merck & Co., and Pravochol from Bristol-Myers Squibb Co. have been allowed to include on the label and in ads that they have the power to cut heart attacks for almost 10 years already.

The changes stem from the results of a company-funded study called the Anglo-Scandinavian Cardiac Outcomes Trial or Ascot, which involved more than 19,000 patients with high blood pressure. It showed that Lipitor reduced the risk of heart attacks and heart-related deaths by 36% compared to the placebo.

Not all experts are jumping on the bandwagon in favor of the new lower levels of cholesterol as recommended by the National Institutes of Health, in conjunction with the American Heart Association and the American College of Cardiology. Some experts say statins are more complex than their status suggests, and like all other drugs they may have some serious negative side effects. It has yet to be proven that the drugs will not have a serious toxicity effect when taken over a 20 year or longer period of time.

Some consumer groups have said the new recommendations are tainted by the influence of drug companies that make statins and finance research on the drugs. One of the consumer groups, the Center for Science in the Public Interest in Washington asserted that many of the experts on the panel that drew up the guidelines had received consulting fees, money for research or other money from the companies that make the statins. The NIH has acknowledged that eight of the nine experts on the panel that issued the recommendations had received financing from one or more or the companies that make statins.

The FDA has granted approval to Schering-Plough Corporation and Merck & Co. to begin marketing Vytorin that will thus become another competitor in the cholesterol drug market. The drug combines the properties of Zocor from Merck and Zetia from Schering to both lower the bad cholesterol number (LDL) while at the same time increasing the good cholesterol number (HDL).

Merck said that it would begin an aggressive marketing campaign to get people to switch to the new drug since its patent for Zocor expires in 2005. Global sales of cholesterol drugs are expected to exceed $21 billion in 2004, with Pfizer's Lipitor being the leader in sales with expected sales of over $9 billion in 2004.

In a study, researchers from Brigham and Women's Hospital in Boston and Harvard Medical School concluded that genes may play an important part in determining who benefits from taking statin medication in the battle against heart disease and failure. All of the 1,500 patients in the study were taking Bristol-MyerSquibb Co. cholesterol statin drug Pravachol.

Ten different genes were used in the study. Patients with a certain common genetic variant had a 22% smaller drop in total cholesterol and a 19% smaller drop in LDL or "bad" cholesterol than those patients with the variant. Bristol-Myers called for further study of all statin drugs in connection with these findings. The relevant genetic variant was found in 7% of the patients studied. Paul M. Ridker who is a director of the Women's Hospital's Center for Cardiovascular Disease Prevention was the lead author of the study.

The investigators will now study the Pfizer's statin medication Lipitor to see if the same results will apply to this medication. Lipitor is the biggest selling drug in the world, with an expected close to $10 billion in sales expected in 2004. There are plans to compare the results of different dosages of the statins to see if there is any correlation to this genetic evaluation.

Proponents of personalized medicine, which is called pharmacogenics feel that this is one of the most important factors that should be used by a physician when he is prescribing medication to his/her patients. SmithKline PLC, has a genetic-research team headed by a former Duke University researcher considered a pioneer in this field. Bristol-Myers is also doing in house research in this field.

Dutch medical regulators, acting on behalf of the 24 members of the European Union issued a warning in connection with some serious side effects involved in the usage of AstraZeneca's statin drug Crestor. Following this warning the FDA issued an advisory warning doctors in the country to carefully read the U.S. label, which has cautions similar to the new European label.

Concern over the usage of Crestor has arisen because of reports of serious muscle toxicity in some patients since its introduction last year. The new label warns doctors to start all patients on a low dose of 10-mgs, and to restrict high doses of 40-mgs to special cases. Public Citizens, a consumer group, petitioned the FDA in March 2003 to remove Crestor from the market, citing seven reported cases of rhabdomyolysis in the U.S., Canada and the United Kingdom.

Rhabdomyolysis is a rare muscle-wasting condition that caused Bayer AG to withdraw its statin drug Baycol after more than 30 patients in the U.S. reportedly got the disease and died while taking the drug. An analysis published in the New England Journal of Medicine in 2002, based on FDA and industry data, found that the reported deaths appeared far more frequently for Baycol than for any other statin.

According to industry figures the sales of Crestor were about $129 million in the first quarter of 2004. Pfizer's Lipitor, the leader of the statin drugs sold about $2.5 billion in the same quarter, while Merck's Zocor garnered about $1.3 billion and Novartis' Lescol had about $173 million in revenues for the quarter.

England became the first country in the world to approve a statin for sale as a generic drug. Experts in England recommended last year that pharmacists should be able to supply their customers with the generic version of Merck's Zocor following some simple recommended checks that would be done in the pharmacy. An advisory panel to the U.S. FDA may consider data in support of allowing nonprescription sales of statins within the next year.

Merck's Zocor lost patent protection in Britain in 2003, and the company is anxious to be the leader for sales of the non-prescription version of the drug so that it can make up for lost sales. McNeil Europe, a division of Johnson & Johnson is expected to launch its generic version of Zocor at the end of June or early July. It will be in doses of 10-mg per 28-day pack and will be called Zocor Heart Pro. Generically the drug is called simivastatin.

Merck and J&J have formed a joint venture in the U.S. to sell Merck's statin drug Mevacor without a prescription sometime next year. Pfizer's Lipitor is the leading prescription drug sold in the world with sales last year exceeding $9.23 billion.

A recent study of the performance shows that there is a positive in the treatment of Type 2 diabetes as a result of the patient taking one of the stain, namely a 40-mg dose of simvistatin. Researchers are now studying the effect on Type 2 diabetes with an even stronger dosage of simvistatin. About 16 million Americans have Type 2 diabetes, and there are about 800,000 new cases detected each year.

As a result of the study new guidelines have been published by the American College of Physicians that call for people with diabetes who are older than 55, and for younger patients who have any other risk factors for heart disease, like high blood-pressure or a history of smoking. According to Dr. Sandeep Vijan of the University of Michigan: "almost everyone with Type 2 diabetes should be on a statin."

The guidelines are based on a review of studies that show that statins reduce the rate of heart attacks and other heart-related illnesses by 22% to 24% among people with diabetes who had average or above average risks of cardiac disease. Dr. Vijan emphasized that controlling hypertension remained the highest priority. Ranking second is the control of lipids, the fat in the blood stream that can affect coronary health, ahead of glucose regulation

Although the HDL level averages about 45 for American men and 55 for American women, is there any proof that having a higher level will actually prevent a heart attack or stroke? On the other hand as many as half of all heart-attack victims have LDL levels that are considered normal. There are three components of a person's total cholesterol level, i.e. LDL, HDL and triglycerides. HDL is the only one of the three where higher is considered better.

In a very small study involving just 19 patients researchers found that an experimental drug from Pfizer Inc. named torcetrapib both increased the HDL and lowered the LDL of the patients. The patients in the study took a 120-milligram torcetrapib pill daily for four weeks; 10 also took the Pfizer's cholesterol lowering pill Lipitor every day. The HDL levels rose an average of 46% in those taking just torcetrapib, and increased 61% in those getting both medications. Six patients took the torcetrapib twice a day in the study's third phase, and their HDL jumped 106%. LDL levels, the bad cholesterol, fell an additional 17% beyond the reduction achieved by Lipitor alone. Side effects in the study were mild.

Dr. Daniel Rader, director of preventive cardiovascular medicine at the University of Pennsylvania, is the study's senior author. He stated: "One of the big questions that we do have with this drug is will using it to raise HDL levels from normal to high actually reduce risk in people who are at high risk?" Research was also conducted at Tufts University. Pfizer, a branch of the National Institutes of Health, the University of Pennsylvania and the New England Medical Center, funded the study.

HDL takes away bad cholesterol, the main ingredient in artery plaques that rupture to cause heart attacks. This study and its results are only the first step in a long process before any definite final results are obtained. But Pfizer has stated that it intends to eventually market the torcetrapib pills, if successful, only in combination in one pill with Lipitor. Patients who use any other cholesterol-lowering drug will not have access to torcetrapib. The combination Lipitor-torcetrapib pilll would have a one-two punch in that it both lowers the LDL levels and increases the HDL level at the same time. At the same time the new pill would protect Pfizer's patent protection for Lipitor, its $9 billion best selling drug in the world.

Pfizer indicated that it intended to actively pursue the issue of HDLs when it acquired Esperian Therapeutics, a tiny biotech startup company for $1.3 billion because if its novel work in connection with HDL products. These include an intravenous drug that might be used to melt plaques in patients having heart attacks. Pfizer will test the combination 60- mg torcetrapib with different doses of Lipitor to see which might be the most effective combination of the two pills. Ultrasound images will reveal whether dangerous plaques have regressed as a result of the treatment. The initial test will be done over a two year period with about 13,000 patients being studied.

The National Institute of Health has announced that it intends to use about 600 medical professionals to spread the word to doctors that diuretics should be the first medication used in the battle against hypertension. These medical professionals, including doctors, will be used in a similar manner to how the drug industry uses "detail " salesmen and saleswomen to help promote their drugs. Some states have adopted this plan in fighting the high cost of Medicaid drugs being prescribed by some doctors when other generic or cheaper brand name drugs can accomplish the same results.

The NIH's plan is going to be carried out over a three-year period of time and also will involve new hypertension guidelines. The study involved some 33,000 patients and is known as the "Allhat" study whose results were published in 2002. The study was led by Paul Whelton, senior vice-president of health-science at Tulane University The study cast doubt about the effectiveness of the statin medications in benefiting or even significantly reducing the chance of a major heart problem. Bristol-Myers statin medication Pravochol was the one used in connection with the "Allhat"study.

The study known as the Allhat study indicated that patients on diuretics had better blood pressure control, fewer strokes and less congestive heart failure than did the other patients who were not on diuretics. The study further determined that those patients who were on calcium channel-blockers had little, to no benefit in lessening the number of heart attacks, or were helped in the prevention of heart-related deaths.

The study has lasted for 10 years, and determined that diuretics are the best first option for people suffering from high-blood pressure. There has been a loud uproar from the medical profession in regards to this opinion. A diuretic costs as little as $36-$96 annually, while a calcium channel blocker such as Novarsc costs about $724 a year, and Accupril, an ACE inhibitor costs about $470 a year. Beta-blockers, which are earlier medications than the ACE inhibitors cost between $240-$667 per year.

An Australian study has given the opposition some factual material to base their dissent on. The Australian study observed 6,083 hypertensive patients over the age of 65 for a median period of 4.1 years. The patients were started on either a diureticof an ACE inhibitor. The Australian government and Merck & Co funded the study. Many physicians feel that a combination of diuretics and ACE inhibitor, Beta-blocker or calcium channel-blocker is the most appropriate was to treat patients suffering from heart problems. Each patient must be treated on an individual basis since there is no hard and fast rule in these situations.

As a follow up to our item about the C-reactive protein (CRP) blood test in this article several weeks ago, the Centers for Disease Control and the American Heart Association have issued guidelines for the usage of this test. The test is not a replacement for traditional cholesterol and blood pressure tests. It should be used for patients whose risk already appears to be high from these other tests.

Are the statins, the cholesterol-lowering class of drugs safe enough to be used without a doctor's prescription? In the year 2000 the FDA considered this question, and the answer that they came up with was a negative one. A joint venture between Merck & Co., and Johnson & Johnson will raise this question again when they seek permission to be able to sell Merck's Mevacor, which is the oldest statin drug, over-the-counter.

Lurking in the background is Bristol-Myers Squibb, which may also seek permission from the FDA to sell its cholesterol lowering statin drug Pravachol as an over-the-counter medication. Please keep in mind that the statin class of drugs had about $12.5 billion in sales last year in the U.S., making them the best selling class of drug in the U.S.

In the accompanying chart we list some of the risk factors, and the levels to consider for being at risk for a heart attack:

Cardiovascular disease was responsible for the death of about 950,000 people in the U.S. last year. This means that one in every 2.5 deaths had some connection to cardiovascular disease. It is estimated that there are about 8 million Americans taking one of the statin drugs. Pfizer's Lipitor is the number one seller, garnering an expected over $6 million in sales for the drug this year.

Although it may seem strange that the drug companies are seeking to sell the product before the expiration of the patents on these drugs, there is a very valid reason in back of their behavior. Recent studies and medical guidelines have shown that more people could benefit from taking the anti-cholesterol drugs. If the drug is sold as an over-the-counter medication, it probably could increase the number of people taking the drug at least twofold. Thus although the price that the medication is sold at would come down sharply, the increase in sales would more than make up for the drop in price.

One of the key questions that needs to be answered when using a statin is how harmful it will be to the liver. Many present users of these drugs have had some negative side reactions when they have taken the drugs. Muscle spasms and bowel irregularity are but two of these negative reactions that are the most common for those who are on the medication.

On the other hand Pfizer might continue to argue for Lipitor as a prescription only medication, advertising that it is "better" than the over-the-counter. Keep in mind that the statins lower the "bad"cholesterol (LDL-low density lipoprotein) when in fact several of the latest studies indicate that elevating the "good" cholesterol (HDL- high density lipoprotein) is much more important in trying to prevent cardiovascular events. Another factor that has come into the equation lately is the level of C-reactive protein.

Most medical professionals feel that a "good" HDL reading should be at least above 40 mg/dl in men and 50 in women. A "bad" LDL reading should be 110 or lower. The greatest benefit would come if the HDL level exceeded 60. Although there has not been too much controversy over the higher the HDL level the better, there is a great deal of controversy over whether or not there is any benefit from having a LDL of less than 110. Many health professionals feel that the HDL level is so important that it can literally wipe out other risk factors, like smoking and being overweight.

Total cholesterol, which is based on a combination of LDL, HDL and triglycerides, should be less than 200 mg/dl. Research has shown that for every one-unit increase in HDL, a person's risk of heart disease drops b as much as 3%. No one is exactly sure why the HDL appears to offer so much protection against heart attacks. Losing weight and quitting smoking are two obvious ways to lift the HDL level. High fat foods lift the HDL but they are associated with heart disease. Cutting down on calories and switching the fats in your diet to monounsaturated fats are better for your heart, and help stabilize your HDL level.

Depending on the type of exercise that you do, can benefit your HDL level also. Weight lifting does not help raise your HDL level but aerobic exercise does. The biggest exercise-induced boost in HDL was found to come from intensive training, such as training for marathons. Moderate alcohol consumption can increase your HDL level also. Niacin a B vitamin can raise HDL by 15% to 30%. Drugs known as fibrates (gemfibrozil) can raise HDL levels by 10% to 20%. Unfortunately once you stop taking a HDL booster drug, it reverts back to its previous level.

In a study funded by Pfizer, that was done at the Cleveland Clinic, researchers found that the people getting Pfizer's Lipitor (atorvastatin) had much lower LDL levels than did those patients who were taking Bristol's Pravachol (pravastatin). Dr. Steven Nissen, who heads the Clinic and is the medical director also asserted that the Lipitor patients also had a slight reduction (-0.4%) in the volume of plaque, while the Pravachol patients had a slight increase (+2.7%) over an 18-month period. Thus in effect the pravastatin did not stop the coronary artery disease, while the atorvastatin did stop it.

Medical experts said that national guidelines were unlikely to be changed until additional studies found that more aggressive cholesterol lowering resulted in a reduced risk of heart attacks and/or deaths. Please keep in mind that AstraZeneca's new statin lowering drug Crestor (rosuvastatin) can lower LDL levels more than Lipitor. According to Merck, its cholesterol lowering medication Zetia (ezetimibe) taken in combination with another type of drug will lower the LDL levels even more than any other statin.

The study also showed that those patients on Lipitor had a drop of 36% in their C-reactive protein levels in the 18-month timeframe while those on Pravachol only had a drop of 5%. In the study, patients were assigned to either 80-mgs a day of Lipitor, or 40-mgs a day of Pravachol. These were the strongest doasges of these drugs at the time the study commenced, but there is now an 80-mg a day version of Pravachol also.

Please see our earlier article on this topic: Beta Blockers, ACE Inhibitors and Statins in the Battle Against Heart Disease or Failure-Part I

We first began to look at heart failure in our article "Cardiovascular Disease: Congestive Heart Failure". Since that original article we have followed up with several other articles on the topic of prescription drugs. In our article "Prescription Drugs and the Cost of Advertising Them" we discussed how on average the cost of advertising prescription drugs is rising at a much higher percentage than is the cost for Research and Development. Please also see our articles " Prescription Drugs and the Elderly" and "Prescription Drugs and Medicare".

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "How to Select a Nursing Home"

By Allan Rubin
Updated May 7, 2008

http://www.therubins.com 

To e-mail: hrubin12@nyc.rr.com or rubin@brainlink.com

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