Beta-Blockers and ACE Inhibitors in the Battle Against Heart Disease or Failure-Part I
Please see Part II of this article: Beta-Blockers and ACE Inhibitors in the Battle Against Heart Disease or Failure-Part II
(4/7/04)- 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 has 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.
The guidelines are as follows: a reading below 1.0 is low risk, 1.0 to 3.0 is moderate risk, and over 3.0 indicates high risk. A report from the University of Cambridge in the United Kingdom was based on an 18,560 patient heart study in Iceland. It found that C-reactive protein did indeed predict heart attack risk independent of other factors. It did find however that the predictive finding was lower than earlier studies had shown. This study used 2.0 as the level for high risk instead of the 3.0 level as called for by the guidelines.
The FDA had previously approved the high sensitivity C-reactive protein (CRP) blood test, which costs about $20 to $50, for those who are at high risk of having a heart attack. Incidentally over one-half of the people who have heart attacks exercise regularly, don't smoke and have normal blood pressure and cholesterol levels. Insurance does cover the test for those who are at high risk of having a heart attack.
There are many physicians who believe that inflammation in the arteries cause heart attacks. The inflammation can lead to formation of plaque, hidden inside the artery walls. Levels of CRP rise when there is an inflammation, so elevated levels may indicate that there is a problem. Studies show that people with the highest CRP levels have a three to six times greater risk of heart attacks compared with those who have the lowest levels.
Researchers led by Dr. Paul M. Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston concluded that women with high C-reactive protein were twice as likely to have a heart attack or stroke as women with high cholesterol. The CRP test was performed on President Bush when he had his annual exam in August. His level was low. About 650,000 Americans will suffer their first heart attack this year.
Most medical professionals consider the global risk score the most reliable tool for estimating the risk of a heart attack. The score is derived from a point-based formula derived from a combination of age, cholesterol level, blood pressure, whether or not the subject has been a smoker, and if the subject has diabetes. The score arose from the Framingham Heart Study, which has tracked the development and progression of heart disease in residents of Framingham, Mass. for the last 50 years.
The main problem with the CRP test is that there is no definitive answer as to what course patients and doctors should follow after seeing the results of the test. As we go on to show in this article, which type of treatment is best for a potential heart attack victim?
The protein is measured in milligrams per liter of blood and the lower the level the better. A high level is a reading of over 4.0. The measures already approved to treat and/or prevent heart attacks also lower the level of protein. These include exercise, weight loss, aspirin, smoking cessation and the use of the statin drugs. According to Dr. Robert Bonow, president of the American Heart Association, the association and Centers for Disease Control and Prevention will meet shortly to issue guidelines on this matter.
The researchers in the Ridker study measured levels of C-reactive protein and LDL cholesterol. They concluded that compared with high cholesterol, high protein was linked to about twice the risk of stroke, coronary disease or cardiovascular death. Their report was based on analysis of blood samples from nearly 28,000 participants in the Women's Health Study.
AstraZeneca PLC announced that Dr. Ridker would conduct a 3 1/2-year study, which will involve 15,000 patients to see if their statin drug Crestor can cut the risk of serious heart problems among patients with high levels of C-reactive protein. The trial will enroll male patients over the age of 55 and women over 65 who have LDL cholesterol under 130 and a C-reactive protein score over two, which indicates a moderate to high risk. Half of the patients will get 20-mgs a day of Crestor, which is known generically as rosuvastatin. The other half will get a placebo. The drug has not been approved for marketing yet in the U.S.
Although Bristol-Myers Squibb's "Prove-It" study seemed to have backfired on its cholesterol-lowering drug Pravachol, it does not seem to have effected sales of the drug according to the earliest data from ImpactRx Inc., a Mount Laurel, N.J., market research firm. The data garnered on a weekly trailing 7-day basis of a network of physicians shows that Pfizer's Lipitor upped its new prescription sales numbers from 27% as of March 4, to 40% as of March 18, the numbers for Pravachol remained about the same. On the other hand AstraZeneca's Crestor seemed to be effected the most, since new prescriptions for this drug fell to 17% from 28% as of March 4.
Since Crestor is more effective than Lipitor in lowering LDL, many analysts and physicians thought that Crestor would be a beneficiary of the study also. Some experts attributed the decline in the usage of Crestor to the fact that the advocacy group Public Citizens issued a call to the FDA to withdraw its approval of the drug because of potentially life threatening side effects. "Crestor is a very strong drug, but doesn't have much hard data to go for it, " said George Dangas, a cardiologist at the Lenox Hill Heart and Vascular Institute.
The Prove-It study, which was sponsored by Bristol-Myers, hoped to show that high-doses (40-mgs) of Pravachol would be more effective than high doses (80-mgs) of Lipitor. The study was conducted at the Harvard Medical School. The lead investigator was Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston and Harvard Medical School. The results suggest that for every 25 patients taking Pravachol, one will die or suffer a serious event that would have been avoided by taking Lipitor.
National guidelines show that the levels of LDL cholesterol should be below 100 milligrams per deciliter in high-risk patients. The Prove-It study of 4,162 patients hospitalized for a sudden attack of chest pain from heart disease would be better off if the LDL was even lower than 100 mgs. When the study started all patients had cholesterol levels at 100 mgs or lower. Those patients who took the Lipitor saw that their LDL level dropped to 62-mgs, compared with the 95-mg level among those who took the Pravachol.
The study found that 26.3% of the patients on Pravachol had either died, suffered a heart attack or had other serious complications of treatment compared with the 22.4% of those on Lipitor. Of the patients on Pravachol, 3.2% died from any cause within 2 years, compared with 2.2% of those on Lipitor, a 28% reduction. Bristol_Myers had previously acknowledged that Lipitor reduced bad cholesterol more, but it theorized that the benefits of LDL lowering began to fade once the levels got down to the 120-125 mgs range.
The test also showed that the Lipitor patients who received high-doses of the drug started showing lower LDL numbers within 30 days of initiation of treatment with the drug. On the negative side of the study was the fact that 3.3% of patients who were on Lipitor had a high level of enzymes that are a predictor of liver problems, compared with 1.1% on Pravachol. Researchers were not sure whether Lipitor's edge over Pravachol was due solely to its cholesterol-lowering power or involved other factors as well. Lipitor proved to be more effective than Pravachol in reducing levels of an inflammatory marker called C-reactive protein. There is a theory that when plaque is inflamed, it is more likely to burst open.
AstraZeneca PLC has launched its new cholesterol-lowering statin drug Crestor, and thus has joined 25 other countries where the drug is now being sold. According to drug analysts, the statin category of cholesterol-lowering drugs is thought to be about $20 billion annually.
Cardiovascular disease is thought to be effected by high cholesterol levels, and is the number one cause of death worldwide. Statins lower the level of harmful cholesterol in the body, and raise the level of good cholesterol. Crestor which is to be taken once a day, will sell for $2.53 a dose, wholesale.
The FDA approved AstraZeneca PLC's Crestor for sale in the U.S. following a yearlong delay caused by concerns about possible side effects. The approval is for dosages up to 40 mgs. Astra announced that it is prepared to spend as much as $1 billion on advertising for the drug. Its main rivals in this market are Pfizer Inc.'s Lipitor with $8 billion in annual sales last year and Merck & Co.'s Zocor, which had $5.6 billion in sales last year.
Lipitor was the number one selling drug in the world last year. Sidney Wolfe, who is a consumer advocate with Ralph Nader's Public Citizen urges caution in connection with the usage of Crestor. There have been some negative side effects associated with the drug such as muscle tics and also kidney toxicity's seen in some studies. As with all statins, patients need regular monitoring for adverse signs associated with taking the drug.
In July 2003, the endrocine and metabolic-drug advisory panel of the FDA voted 9-0 to approve AstraZeneca PLC's new cholesterol lowering drug Crestor. The review process had been delayed about a year because the FDA had requested additional clinical data.
Crestor is the newest and most potent of the cholesterol lowering drugs known as statins. Statins lower cholesterol by slowing an enzyme in the liver that produces LDL, the "bad" cholesterol that delivers fat to the arteries. Heart disease is the leading cause of death in the Western world. Safety issues were of primary concern to the panel especially in connection with the 40-mg dosage of the drug. There was a question that had arisen in connection with patients who took the 40-mg version of the drug having bad kidney and muscular side effects.
The panel did recommend the drug even in the 40-mg dosage because it was felt that this dosage level could help the sickest patients. The panel did call for patients on this dosage to be monitored closely, and for the company to do postmarketing studies. The FDA decided last year not to approve the 80-mg version of the drug, since this dosage was too risky.
The 40-mg version of Crestor is more powerful than the highest dosage of 80-mg for Pfizer's cholesterol fighting drug Lipitor. Experts feel that Crestor lowers bad cholesterol more than any other drugs in the class on a per-milligram basis, according to an FDA data report given to the panel. Most patients will be started on the 10-mg dosage level of Crestor, while patients with very high cholesterol levels will be given the 20-mg version of the drug. It is estimated that Lipitor will do over $8 billion in sales this year. The drug has been approved in 23 countries not including the U.S. and Japan. Astra licensed the drug from the Japanese company Shionogi & Co. in 1998.
A study, involving more than 12,000 patients showed that giving a drug called perindopril could reduce the chances of heart-related deaths or heart attack by 20%. The drug is one of the drugs in the ACE inhibitor category, but we caution that Servier SA of France the manufacturer of the drug, is also the company that sponsored the study.
Kim Fox, a cardiologist at Royal Brompton Hospital, London, and co-chairman of the study, presented the findings of the study at a meeting of the European Society of Cardiology in Vienna. A majority of the patients were already on recommended therapy, including aspirin, a beta- blocker and a statin, which is a cholesterol lowering drug.
In a trial that compared Pfizer's Lipitor and a placebo it was determined that Lipitor does significantly reduce the risk of strokes and heart attacks in patients with diabetes. The four-year trial was stopped in min-stream to allow all study patients to receive Lipitor. The trial included 2,800 patients in Britain and Ireland with Type 2 diabetes and no previous history of heart disease or stroke.
In a study of Pharmacia Corp.'s blood-pressure drug epelerenone (brand name Inspra) conducted on more than 6,600 patients who showed signs of developing heart failure within two weeks of suffering a heart attack, the drug improved survival by about 15%. About half of the patients were given epelerenone in combination with beta-blockers and ACE inhibitors. The other half got the standard treatment of beta-blockers and ACE inhibitors alone.
The findings reinforced the idea that a hormone called aldosterone plays a major role in the damaging effects of heart failure, and that blocking its action offers a compelling treatment strategy. The results of the study was presented at the annual meeting of the American College of Cardiology held this year in Chicago. In addition to the overall survival benefit, patients given eplerenone had a reduction in deaths from heart disease and reduced hospital-related stays. It also helped to reduce deaths due to sudden heartbeat irregularities by 21%, said Bertram Pitt, a University of Michigan researcher who directed the study. The blocking of aldosterone is similar to the results shown in some studies involving the generic drug spirononlactone.
Eplerenone's major benefit over spiranonlactone is a lack of sex-related side effects for both sexes. Both however can raise potassium levels in the body to dangerous levels, so its use has to be monitored closely by the treating doctors. Eplerenone was approved as a blood pressure treatment in November of 2002, but Pharmacia has not released the drug yet.
The Wall Street Journal issued dated November 3, 1999 contained a terrific article entitled "Heart-Failure Patients Get New Hope, Thanks to a Forgotten Drug" by Ron Winslow. The article tells the story of a 40-year-old heart drug that is no longer on patent named Aldactone. The company involved with the drug is G.D.Searle a division of Monsanto, which in turn has become a division of Pharmacia. One of the key players in this still evolving story is Alfonso Perez their senior medical director.
When first introduced in the late 60s the drug was used to block the action of a hormone called aldosterone. Doctors had determined that a common trait in failing hearts was a tremendous amount of fibrous connective tissue in spaces between the cells of the heart. It was determined that these fibrous tissues caused a constrictive force upon the muscles of the heart.
Through some tedious testing it was determined that it was aldosterone hormone that caused the growth of this fibrous tissue. The Searle researchers began a test in March 1995 involving 1,663 congestive-heart-failure patients in 15 countries. The test involved giving half the patients a diuretic and an ACE inhibitor while the other half received Aldactone as well as the diuretic and an ACE inhibitor. The test was supposed to run till the end of 1999.
The test was halted in August of 1998 because of the substantial decrease in the death rate of those subjects who combined the Aldactone with the other medications over those who did not take the Aldactone. It was determined that although the ACE inhibitors had originally blocked the aldosterone production, once the circulatory system was stable the ACE inhibitors served to stimulate the fibrous production resulting from the aldosterone hormone.
The Aldactone would serve as a preventative for the fibrous tissue growth. Searle has subsequently developed a "better and cleaner" Aldactone, which is named epelerenone, which is presently undergoing testing for the treatment of high blood pressure and heart failure. Searle will protect this latter drug under patent. Incidentally the generic spironolactone sells for about $10 for a month's supply. Aldactone sells for about $40 for a month's supply.
According to a study, led by Paul Whelton, senior vice-president of health-science at Tulane University, doubt has arisen 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 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 federal study has lasted for 10 years, and has 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 that is now making its opinion heard in the medical community. 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.
Johnson & Johnson's new form of stent, called Cypher is stirring up quite a debate in the area of both the treatment of heart disease and the surging cost of medical treatment in this country. Many medical experts feel that the new device is so superior to anything else around that it is well worth the cost. The Cypher stent costs about $3,100 apiece. Boston Scientific's stent, which is also chemically treated to prevent blood clotting costs about $2,900. A non-chemically treated stent costs about $300 apiece.
Yet the cost is so high for the new stent that the medical community is considering asking the patient if he/she wants to receive it, and if they do, are they willing to pay the premium that the stent will cost. The stents that are now being used in artery-clearing procedures cost between $900 and $1,200. The J&J Cypher stent, which is coated with a tiny amount of a drug that gradually seeps into surrounding tissue and prevents the formation of scarring that can reclog the artery is expected to cost about $3,100 per stent. About 160,000 Americans have to undergo additional procedures after having the first artery clearing one. J&J argues, that in preventing the need to undergo additional clearing procedures, the new stent in effect will thereby save many millions of dollars in medical costs to the patients that use it.
An estimated 15 million Americans are now taking cholesterol drugs, commonly called statins. As a matter of fact the statin category of drugs take in more sales than any other type of prescription medication. There is however a growing concern that we do not know as much about them as we should.
Many patients taking the statins are beginning to report a wide range of side effects including muscle pain, weakness, fatigue, burning and tingling in the hands and feet, memory problems and erectile dysfunction. Many of these problems are associated with the aging process so they had not been reported by a lot of the people who were on these medications. An estimated 5% to 15% report these problems.
A simple blood test is used to determine whether the statin is the culprit in muscle pain. The test looks for creatine kinase, or CK, an enzyme released when muscle damage occurs from any cause. An elevated CK level prompts the doctor to lower the dose or change the drug. Unfortunately however this is not proving to be the case in a lot of the statin drug situations with the patients. Patients with normal CK levels are reporting many of the adverse symptoms mentioned above. The National Institute of Health is sponsoring a large study , led by the University of California, San Diego to assess the variety of reactions being reported by patients on statin medications.
According to a study, led by Paul Whelton, senior vice-president of health sciences at Tulane University, put into question the fact that one of the statins, namely Bristol-Myer Squibb's, Pravochol failed to improve survival rates or prevent heart attacks when compared with patients who got what was called "usual care". It was the first time in a large study that one of the statin class of medicines didn't show a survival benefit or significantly reduce the chance of major heart problems. The large federal study of patients with high blood pressure is known as Allhat.
According to the FDA website listing Paragraph IV patent certifications, a patent challenge was recently filed against Pfizer's Lipitor for the 10-mg, 20-mg, 40-mg and 80-mg doses. Lipitor sales in 2002 are expected to be in the $5.3 billion range.
Pfizer lists 5 patents in the Orange Book that expire between 2009 and 2015. Thirty-five percent of Pfizer's worldwide pharmaceutical sales are at risk (on a stand-alone basis) for Paragraph IV challenges. In addition to Lipitor, there are ongoing patent challenges to Neurontin, Norvasc, Glucotrol XL and Accupril.
AstraZeneca announced that the Medicines Evaluation Board in the Netherlands had approved its cholesterol-lowering drug, Crestor, for the management of hypercholesterolaemia and mixed dyslipidaemia. Crestor has been approved at 10, 20 and 40-mg dosages. Many independent experts have spoken about the fact that Crestor may be the best of the statin drugs that will be available to safely reduce high-levels of cholesterol.
The approval of Crestor in the U.S. remains dependent on the results of ongoing studies of 40-mg Crestor, and the FDA will not be affected by the Netherlands ruling. Since the Netherlands is a member of the European Union, the other countries in the Union will give recognition to Crestor also.
After a 10-month review, the FDA approved Schering-Plough Corporation's cholesterol lowering drug Zetia (ezetimibe). Schering will market the drug through a joint venture with Merck. Studies showed that Zetia further reduced cholesterol levels when combined with Merck's Zocor or Pfizer's Lipitor.
Zetia inhibits the absorption of cholesterol in the intestines, unlike statins, which work mostly by blocking cholesterol production in the liver. The clinical trials for Zetia showed that the combination of a statin plus Zetia cuts cholesterol more effectively than a statin alone. The companies intend to develop a pill combining ezetimbe and Zocor, which is Merck's biggest selling drug.
A study done by a team based at Oxford University and led by Dr. Robert Clarke concluded that levels of homocysteine in the blood might not be very helpful in predicting heart attacks. Dr. Kilmer McCully did a study in 1969 that found that high levels of the chemical might be a cause for arteries to clog.
Dr. Clarke's study was a "meta-analysis", blending data from 30 studies. It looked at the records of almost 17,000 people who collectively suffered 5,073 heart attacks and 1,113 strokes. His study found after allowing for other risk factors such as high blood pressure and smoking, that a person who lowered his homocysteine level 25% cut the heart-attack risk 11% and the risk of stroke by 19%. The earliest studies done in the70's on patients who had a heart attack or stroke, found an extremely high correlation with the homocysteine levels.
One study found that 5% of patients with the highest levels had a greater than three times the risk of the others. Later studies done on healthy male and females found that after a five-year period of time that there was a much smaller correlation. According to Dr. McCully that "Even if the test method isn't perfect, it does give some information. And it does show some connection between homocysteine levels and risk."
Does the lowering of cholesterol levels reduce or even prevent heart attacks or strokes? This is an open question that still has to be answered. A study of 20,000 patients with high blood pressure began in 1998 in several European countries. Study participants were required to have hypertension and at least three other risk factors, such as being 55 years of age or older, smokers or have diabetes.
The study called ASCOT was designed to compare the effects of newer anti-hypertensive medicines with standard therapies in reducing cardiac events. Half of the patients enrolled in the study received either a 10-mg dose of Lipitor or a placebo to measure the effects of lowering cholesterol in patients who had high blood pressure and cholesterol levels that were normal or slightly elevated.
According to Dr. Joe Feczko, President of Worldwide Development at Pfizer, "These initial results from the ASCOT study suggest a clear cardiovascular benefit from diligently lowering cholesterol levels in this particular population of patients with high blood pressure."
In a study presented at the European Society of Cardiology meeting in Berlin, AstraZeneca's cholesterol lowering drug Crestor proved to be more effective than Pfizer's Lipitor. According to an announcement from Astra, Crestor consistently showed greater reduction in LDL cholesterol than did Lipitor across a range of doses. This new data will be included in the presentation that the company makes for the approval of the drug from the FDA later this year.
Astra previously had announced that there would be a further delay in the launch of its cholesterol lowering statin drug Crestor. The delay appears to be related to high-dosage (80-mg) patients. The company hopes to provide the new data to the FDA by the end of the first quarter in 2003. It normally takes the FDA at least 6 months to review the new data. This in turn means that the earliest that the drug can be on the market would be in the fourth quarter of 2003. AstraZeneca said that it no longer intends to seek approval to sell an 80-mg version of the drug.
AstraZeneca received an "approvable" letter from the FDA in June of this year but the company declined to reveal the contents of the letter at the time. An "approvable" letter usually describes the remaining conditions that need to be met before a drug can be put on the market.
Although high-dosage patients represent a small percentage of the market, a clean profile is critical for the drug since it will be trying to take market share away from the statins that have already been in the market for several years. The delay will further throw into doubt the safety of the drug versus the other statins that have been on the market for several years now.
AstraZeneca had presented the results of its Phase III results at a meeting of the American College of Cardiology. The results seemed to demonstrate Crestor's superior efficacy and confirmed its status as the "superstatin". There has been a great deal of conjecture as to whether or not Astra will market the drug by itself, or if it will find a co-partner in such a venture. Bristol-Myers and American Home Products have been mentioned as possible co-marketing partners with Astra. Astra has a lot riding on Crestor since they will be losing their patent on Prilosec, its anti-ulcer drug which was the best selling drug in the U.S. last year with sales of $4.2 billion.
The FDA has refused to approve Vanlev, even as a drug of last resort in the battle against high-blood pressure. Trial of the drug showed that usage of the drug led to facial swelling (angioedema), which in turn could lead to life-threatening airway constriction. People at the highest risk for cardiovascular problems-Afro-Americans and smokers were much more likely to experience angioedema.
Vanlev was originally supposed to have been launched in June 2000 and it held a great deal of promise in the battle against cardiovascular disease and stroke. Unfortunately the study of the drug failed to prove its superiority and Bristol Myers has halted further studies on the drug. The drug represents a new class of drugs for hypertension, the vasopeptidase inhibitors. Vasopeptidase inhibitors have a dual mechanism of action because they block two enzymes, ACE (angiotensin converting enzyme) and NEP (neutral endopeptidase).
Vanlev is aimed at significantly reducing both systolic blood pressure (the high number) and diastolic blood pressure. Most anti-hypertensives have little affect on the systolic pressure. The drug filed in December 1999 and received expedited review status.
The company originally announced on April 19th, 2000 that they had withdrawn their application for the drug. The withdrawal was an outgrowth of questions raised by the FDA because of the severe reaction in 4 patients on the drug. The reaction closed down their airways due to angioedema, which is a swelling of the lips, cheeks and tongue which in turn causes constriction in the airway passage.
Recent studies seemed to indicate that the cholesterol lowering statin drugs helped patients live longer lives and avoid heart attacks after undergoing angioplasty procedures. In a four-year study involving 1,677 patients the drug fluvastatin reduces the risk of heart attack, death and other heart problems following the procedure by 22%. Dr.Patrick Serruys. Professor of interventional cardiology at Erasmus Medical Center, University Hospital, in Rotterdam, Netherlands led the study. The patients on average had normal cholesterol levels at the time of their angioplasies, but were given the cholesterol lowering drug anyhow.
Researchers reported that Pharmacia Corp.'s experimental drug eplerenone may be effective in treating high blood pressure for African-American patients. In the study that compared this drug to Merck & Co.'s losartan over a16-week period, eplerenone (which is an improved version of Aldactone) blocked the hormone aldosterone more effectively, and lowered the blood pressure as well. The aldosterone hormone regulates salt and water retention in the body.
Several studies have shown that ACE inhibitors are less effective in blacks than in whites. Black Americans are at a much higher risk for stroke and advanced kidney disease than whites-ailments that result in part from hypertension. Elijah Saunders, professor of medicine at the University of Maryland School of Medicine, Baltimore led the study that was done on 551 patients of whom 348 were blacks.
Lovastatin is a generic version of the cholesterol lowering class of medications called statins. It costs about $36 for 30 pills (30 mg) versus the $68 for Mevacor and about $59 for Lipitor. Remember to ask your doctor if this generic version of the drug is one that you may use if you have a high cholesterol count.
Many questions have arisen however in connection with the side effects associated with taking statins. An article in the February 1, 2002 edition of the Wall Street Journal, entitled "Cholesterol-Drug Use Soars, Raising Questions About the Side Effects" looks into this issue. The most common side effects that users of the statins complain about are muscle aches and memory loss. Another common complaint is irregular bowel movements. Pharmaceutical companies dispute the notion of memory loss and are actually studying the possibility of using statins to treat Alzheimer's disease.
The University of California at San Diego is presently studying the side effects of statins under a $4.4 million grant from the National Institutes of Health. Approximately 1,000 patients are involved in the blind study in which they are taking Zocor, Pravachol or a placebo. Some of the patients have quit the study because of irritability, pain or memory problems.
The top selling statins include Merck & Co's Zocor (about $6.7 billion in sales in 2001), Bristol-Meyers Squibb Co.'s Pravachol and Pfizer's Lipitor. AstraZeneca has also added its name to the battle over the $13 billion global market (about $10 billion in sales in the U.S. last year) for drugs that can reduce risk of heart attack by lowering cholesterol with its drug which is still in trial phase called Crestor. Lipitor incidentally racked up $4.72 billion in sales last year. At present about 13 million Americans take a cholesterol-lowering drug. The results of a clinical studies involving nearly 80,000 patients using Lipitor is due to be reported on over the coming months. So far Pfizer has spent almost $500 million on these studies.
Merck was recently given a 6-month extension for the patent life of Zocor by the FDA under the pediatric extension provision that Congress passed in 1997. This means that Merck's patent for Zocor will not expire until June of 2006. This provision in the law is due to expire, unless renewed by Congress, by the end of this year.
Although this series of articles deals with the battle against heart disease or failure, Alzheimer's disease is also a topic on which we have written many articles. It would be a real added bonus if further reinforcement is given to some studies that indicate that the cholesterol-lowering drugs called statins prove to be effective in the battle against Alzheimer's disease.
Robert Green, a Boston University neurologist and epidemiologist headed a study group that concluded that taking statins resulted in a 79 % reduction in a person's risk of developing Alzheimer's. The researchers examined the risk factors and medication history in 912 people with probable or definite Alzheimer's disease, and 1,669 of their family members who did not have dementia. Dr. Green says the statins interfere with the production of the protein beta-amyloid, which is thought forms a covering of the brain of people with Alzheimer's disease.
The results of a study headed by Hershel Jick, director of the Boston Collaborative Drug Surveillance Program, Lexington, Mass. seemed to indicate that the popular cholesterol lowering drugs called statins may also help reduce a person's risk of developing Alzheimer's disease.
Analysis of the data base of patients who were 50 years or older found that those who were prescribed statins were 70% less likely to develop dementia than those in the other group. Statins work by lowering levels of low intensity lipoprotein, or LDL, the "bad" form of cholesterol that builds up in the walls of coronary arteries causing atherosclerosis.
The results of the study have been published in the medical journal Lancet. The patients ranged in age from 50 to 89 and were tracked for a 6-year period of time ending Jan.1, 1998. The final analysis was based on 285 patients who were diagnosed with dementia during that time and another 1,080 who served as controls. Dr. Jick and his associates examined the medical records of more than 60,000 patients culled from a database of more than 3 million residents of the United Kingdom. Dr. Jick's surveillance program is affiliated with Boston University School of Medicine and was supported by grants to the program from Bristol-Myers.
A 5-year trial involving Merck's Zocor is nearing completion now and may offer some additional information on the result's of Dr. Jick's study. According to Jonathon Tobert, executive director for clinical research at Merck Research Laboratories "it would be plausible if statins had an effect on dementia".
In an interesting development involving the whole area of drug pricing, Pfizer, Inc. the world's largest drug company announced that the Justice Department was investigating its pricing for Lipitor for the years 2000 and 2001.
Lipitor, which is a drug used to treat high cholesterol levels, is Pfizer's biggest selling drug. The investigation concerns whether or not the payments to certain health plans and pharmacy benefits managers should be considered rebates or grants. If they are considered rebates the government should have gotten a cheaper price for the Medicaid patients who used the drug during the period covered by the investigation.
According to an article that was published in the Mayo Clinic Proceedings men over 60 who took aspirin or another non-steroidal anti-inflammatory drug daily were half as likely as those who didn't to be diagnosed with prostate cancer during a six-year Mayo Clinic study. The benefit was even greater for men over 70 who took the daily dosage of aspirin.
Dr. Rosebud O. Roberts led the study, but she stated that she considered the study's results to be too preliminary to be a basis for treatment recommendations. She further stated that she suspected that the older men showed greater benefits from taking the aspirin because they have been taking the aspirin for a longer period of time, and that the drug has a cumulative benefit.
The NY Times issue of April 18, 2000 had an excellent article written by Abigail Zuger entitled " Aspirin: Superhero or Problem Pill ". In the article she states " Aspirin continues to show tantalizing promise for medical conditions far afield from its original uses: recent studies suggest it may be able to help prevent dementia, stroke, (and) even cancer."
She refers to the fact that ambulances and emergency rooms now carry and administer aspirin for heart patients as part of their standard procedures. "When aspirin is given to a person having a heart attack, it lowers risk of death by about 25 percent, and risk of a second heart attack by 50 percent." We do not know where she derives these figures from but everything that we have read on this topic leads us to concur with the statement that: "Aspirin's benefits for men and women with heart disease remain unchallenged."
The article further discusses a study undertaken in the 1980's that was conducted on 22,000 healthy male American doctors over the age of 45. Half of the group took an aspirin tablet a day, while the other half was given a placebo. "After 5 years, the aspirin group had 44 % fewer heart attacks than the other".
Many healthy men refused to participate in the study because of possible intestinal problems that may arise as a result of regular usage of aspirins. The group that used the aspirin had almost twice the rate of strokes caused by bleeding into the brain than did the placebo group. A British study was not able to concur with the results of the American study. A study testing results of aspirin usage for healthy older women has not been finalized yet, with the results not due until 2002.The article also discusses the possible beneficial effects from aspirin usage in the fight against dementia, strokes and cancer prevention.
Just because you have a "normal" cholesterol level does not exempt you from having a heart attack. Just about one half of the people who have a heart attack have normal cholesterol levels. About 150,000 people died last year who had no prior history of heart problems. The National Cholesterol Education Program of the National Heart, Lung and Blood Institute (a division of the National Institutes of Health) has established new guidelines. To see who should be on a cholesterol lowering diet and what the diet consists of please go to www.nhlbi.nih.gov.
An interesting development seems to be taking place in connection with Eli Lilly and Co.'s osteoporosis drug Evista , which is generically known as raloxifene. According to a study done at the University of California at San Diego and elsewhere, the drug sharply reduced (40%) the number of heart attacks and strokes among the older women taking the drug.
Recent research also pointed to a sharply lower rate of breast cancer among women taking the drug. Since it hit the U.S. market in 1998 Evista has not met the sales figures that were originally projected for the drug. Lilly can not promote the drug for any of these other uses since the FDA has approved it only in connection with osteoporosis. Scientists at Emory University in Atlanta are now conducting a much larger study on Evista and its effect on strokes and heart attacks in older woman.
In a study involving 20,536 patients in 69 hospitals in England, it was found that the cholesterol lowering drugs reduce the risk of a heart attack or stroke in high-risk individuals by about one-third. The study was begun as a pilot project in England in 1987, and has been paid for by the British government's Medical Research Counsel, the private British Heart Foundation and by Merck which makes Zocor and Roche. The study was expanded in 1994 and will continue for several more years. Dr. Rory Collins led the researchers for the study at Oxford University.
The study used the cholesterol- lowering statin simvastin, or Zocor, and involved a large number of women, elderly people, diabetics and people with average or below-average cholesterol readings. The study also showed that using the popular anti-oxidant vitamins C, E and beta-carotene, did not prevent heart attacks or strokes. It is estimated that about 25 million people are now taking statins.
According to Dr. Collins, who is a cardiologist and epidemiologist,the most surprising result of the study was the finding of the definite reduction in risk of stroke from the use of a cholesterol reducing statin drugs. He said that blood cholesterol levels had been strongly linked to the risk of heart attack, but not to the risk of stroke. He further stated that the findings apply only to those with risk factors for heart attacks and strokes, and not to other people.
Although simvastatin was the drug used in the study, Dr. Collins felt that the same results would ensue from the usage of the other statin cholesterol-lowering drugs. He also felt that the longer people took the drug, the greater the benefit. Many of the patients were also taking standard treatments like aspirin and blood-pressure drugs. The benefits from using the statins were in addition to the benefits that would ensue from taking these other drugs. He would not advise using the statins for patients without risk factors for heart attacks and strokes, or for people younger than 40.
The drug companies had no say in how the money for the study was spent, the day-to-day operation of the study, the analysis of the data or the way the findings were reported. The first statin to reach the market, Merck's Mavacor, goes shortly.
Preliminary research has indicated that patients taking the ACE inhibitor ramipril, which is sold under the name of Altace reduced their risk of diabetes by more than 30%. The study involved 5,720 patients, 55 and older with vascular disease or other diabetes risk factors. Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, led the researchers. The participants received a placebo or ramipril for an average of four and one-half years. Diabetes developed during the study in 102 people in the ramipril group, 3.6%, compared with 5.4% of patients with the placebos.
The patients reported that diabetes had been diagnosed in them, since the study did not attempt to confirm the diagnosis. Aventis Pharmaceuticals, the manufacturer of rampiril (Altace) was one of the financers of the study. People with kidney disease from high blood pressure have a better chance of reducing the risk of kidney failure if they take an angiotensin-converting enzyme (ACE) inhibitor, according to a National Institutes of Health study in the "Journal of the American Medical Association" on June 6.
The African American Study of Kidney Disease and Hypertension (AASK) found that the ACE inhibitor ramipril (Altace) slowed kidney disease by 36 percent and slashed the risk of kidney failure and death by 48 percent in patients who had at least a gram of protein in the urine. The drug was compared to the dihydropyridine calcium channel blocker amlodipine (CCB, Norvasc(r)). Results were not related to blood pressure control, which was comparable between study groups.
ACE inhibitors have been the preferred treatment for kidney disease of diabetes since 1994, and now AASK doctors are recommending it for kidney disease because of hypertension, especially for people who also have protein in the urine.While CCBs help many patients, particularly African Americans, control blood pressure and reduce the risk of stroke and heart disease, patients may need an ACE inhibitor to protect the kidneys.
News in connection with promising new developments in the battle against heart disease and failure is breaking almost even faster than the Internet can keep up with. One such development involves the usage of an ACE inhibitor (Angiotensin-converting-enzyme inhibitors) named ramipril in conjunction with other drugs such as aspirin, beta-blockers and lipids in preventing heart failure. The drug costs about 85 cents a day to take, and is marketed in the U.S. by King Pharmaceuticals Inc. of Bristol, Tenn. as Altace. A study has indicated that many of thousands of people's lives amongst the 10 million coronary risk individuals in the U.S. can be saved through usage of the drug.
The study was conducted using 9,297 high-risk heart patients 55 years or older. The participants had a least one high risk factor (high blood pressure, increased cholesterol level, low high-density lipoprotein cholesterol or to be a cigarette smoker) for heart disease or stroke. The individuals in the study had not suffered from heart failure.
Salim Yusuf, director of cardiology at McMasters University, Hamilton, Ontario headed the study which was financed by the Canadian government and by the drug company Hoechst Marion Roussel of Kansas City, Mo. The drug has been marketed the last 8 years to combat high blood pressure. The study was meant to last for 5 years, but was stopped ahead of schedule because the safety monitoring committee found a clear benefit from ramipril.
Ramipril is one of 11 ACE inhibitors on the market. It specifically is aimed at the high blood pressure market and it is not known at this time whether or not the other ACE inhibitors will show the same result. ACE inhibitors relax or dilate the blood vessels by blocking a protein known as angiotensin-converting enzymes, which among other things help regulate blood pressure. Dr. Yusuf said other research indicates that angiotensin plays an important role in causing fatty deposits in the coronary arteries that rupture and cause heart attacks.
Dr. Yusuf said that doctors should consider prescribing ramipril for those who take aspirin to prevent heart attacks. The study indicated that ramipril (10 mg once per day orally) reduced the risk of death, heart attacks, and strokes by about 20 to 25 % in a broad range of high-risk patients.
The findings were published in The New England Journal of Medicine's, Jan.20th, 2000 edition. The study also indicated that those suffering from diabetes could also benefit from the drug. We would like to point out that the chemical structure of 11 ACE inhibitors on the market differ to some extent from each other. The mechanics of diabetes differs from that of high blood pressure.
A study done by Canadian researchers of ramipril that was reported on in the journal Circulation indicated that it can slow the buildup of the plaques that clog the carotid arteries in the neck and lead to strokes. Interestingly enough a group of Swedish researchers led by Dr. Goran Berglund of Malmo University, reporting on the beta-blocker metoprolol, found that it slowed the rate of progression of the buildup of the plaques that clog the carotid arteries in the neck by 40%.
Dr. Yusuf's team also studied the effect of Vitamin E on a group of 4761 high-risk heart patients for a period of 4.5 years. They concluded that the ingestion through food and in supplements of Vitamin E over the 4.5-year period of time had "no apparent effect on cardiovascular outcomes. (N Engl. J Med. 2000; 342:154-60.)"
A study done at the Wake Forest University School of Medicine, headed by Curt D. Furberg, a physician and professor at the school concluded that calcium channel blockers are less effective in preventing heart attacks and congestive heart failure than other blood pressure pills. Pfizer's Norvasc is the leading calcium channel medication with annual sales of more than $3 billion in 1999. The study concluded that patients who take calcium channel blockers face a 27 % higher risk of heart attack than patients who are on other blood-pressure pills. The study further indicated that the patients on calcium channel blockers faced a 26 % higher risk of heart failure than patients who are on ACE inhibitors, beta-blockers and diuretics
With Baycol, the cholesterol-lowering drug made by Bayer being withdrawn from the market the following chart shows the other leading drugs available in this area:
Source: Deutsche Bank Bayer
Early results show that Pfizer's Lipitor has captured almost 40% of the former Bayer's Baycol users. A battle royal is now going on among the cholesterol lowering prescription drug companies to replace Bayer's Baycol as the drug of choice. In a page and one third ad in the August 20th edition of the NY Times, Bristol offered a coupon to be used by the former Baycol users along with the patient's doctor's prescription, for a free 30-day supply of its drug Pravachol.
On the other hand Pfizer had a page and one-third ad in the same edition extolling the virtues of its cholesterol-lowering drug Lipitor. Please keep in mind Novartis is offering a free 60-day supply of its cholesterol lowering drug Lescol if you fill out a coupon which you submit along with your doctor's prescription to a participating pharmacy. Merck has taken out a page and one third ad aimed at the former Baycol user which tells you to ask your physicians for free samples of their drug Zocor. Also please keep in mind that AstraZeneca's Crestor may be on the market in about 1 1/2 years, and early indications seem to show it has advantages over the other statins.
Doctors and researchers are trying to find new tests to be able to detect heart disease sooner. A recent article in the Wall St Journal entitled "New Tests Go Beyond Cholesterol to Find Heart-Disease Risks." "Electron beam tomography (EBT) scans artery walls for calcified plaque buildup, an early sign of heart disease. Blood tests can monitor c-reactive protein, fibrinogen, homocysteine and Lp(a) levels, all of which may signal heart disease. Advanced cholesterol screening methods can also provide more information."
The article goes on to point out however that insurance companies may not be willing to pay for these tests unless there is a prior family history of heart problems. Although these tests may show that there is increased risk of heart problems, methods to treat these problems may not be available. Then there is the VAP test that breaks down the readings of LDL, HDL and triglycerides levels to lipid subclasses that might be a factor in heart disease.
Last year cardiovascular disease lead to the death of more than 505,000 woman in the U.S. This was the number one cause of death amongst woman in 2000. This compares with 250,000 woman who died of cancer, which was the number two killer of woman in 2000. Thus one out of every two deaths of women resulted from heart disease or stroke compared to 1 in 25 who died from breast cancer.
Researchers have found that women are much more concerned with cancer than they are with heart attacks and strokes. This may arise from the fact that heart disease sets in about 10-years later in women than it does with men (age 55 for women compared to age 45 for men). Statistically it has been determined that one year after a heart attack, 44% of the women will die versus 27% of the males.
For some unexplicable reason heart attacks show different symptoms in women than they do with men. The pain from the heart attack shows up much lower in women's chests than they do with men, so it may seem as if it is merely a stomach pain. Nausea, extreme fatigue and back pain also may occur. Women should be made aware that they should be following their cholesterol count much more closely.
Women should also pay special attention to their triglyceride levels, which are a more significant risk factor for women than for men. The NIH has developed a calculator for both women and men to help determine their risk for heart attack over the next 10 years. To find the calculator, go to http://www.nhlbi.nih.gov/guidelines/cholesterol and click on patient information.
Science has been aware of the fact that blacks are more than twice as likely to suffer from heart failure, as are whites. The question continues to perplex scientific researchers. Two new studies reported on in the New England Journal of Medicine provided no answers to this question, but did come up with some interesting information in this matter.
In one of the studies, usage of Vasotec an ACE inhibitor made by Merck & Co. led to a 44% reduction in hospitalization for white patients suffering from heart failure, but provided no decline in hospitalizations for African-American patients with the same condition.
In the other study that was done on Coreg, a beta-blocker that is marketed by GlaxoSmithKline, the drug reduced the risk of death or hospitalization by 48% among blacks and 30% among non-blacks. This contrasted sharply with a study done on another beta-blocker, bucindolol, which failed to show any significant benefit to blacks.
According to Clyde W. Yancy, a cardiologist at the University of Texas, Southwestern Medical Center in Dallas "There is virtually an epidemic of heart failure among African-Americans". Derek V. Exner of the University of Calgary in Alberta led the study of Vasotec.
In March of 1998 Sanofi-Synthelabo SA and Bristol-Myers Squibb Co., co-marketed the anti-clotting drug Plavex (clopidogrel) for short-term use in patients who have undergone balloon angioplasty and stent procedures to open obstructed coronary arteries. The drug became a blockbuster racking up sales of $1.19 billion in 2000.
According to a study directed by Salim Yusuf, director of cardiology at McMaster University, Hamilton, Ontario Playvex when taken continuously also reduces the chances of a new heart attack, stroke or death by 20%. The study was conducted on over 12,500 patients in 28 countries. The drug is targeted at the estimated 2 million Americans who report to hospitals each year with unremitting heart pain, which is usually a precursor of a heart attack.
Plavex costs about $3 per pill and now may be prescribed for more of the elderly population. There was one significant negative side effect in connection with its usage, namely a 30% increase in major bleeding versus the trial group that took only aspirin. Thus Plavex has an increased cost over aspirin and a greater risk of increased bleeding than does aspirin. Remember also that aspirin in and of itself has an increased risk of causing bleeding.
We have been keying in on the issue of beta-blockers and ACE inhibitors. A long-held assumption that beta-blockers shouldn't be used in patients with severe heart failure or heart-attacks has been challenged as a result of two studies using the drug carvedilol.
This drug is a beta-blocker co-marketed in the U.S. by GlaxoSmithKline PLC and Roche Holding under the brand name Coreg. Roche is the sole marketer of the drug throughout the rest of the world under the brand names Coreg, Dilatrend and Kredex. The study was stopped after a periodic review by an independent monitoring board, which found that patients taking carevedilol had a death rate at least 34 % lower than patients not taking the drug.
Milton Packer, director of the Heart Failure Center at Columbia University College of Physicians and Surgeons chaired the committee that directed the study involving the heart-failure patients. Henry J. Dargie, professor of cardiology at Western Informary in Galsgow, Scotland, headed the study involving the heart-attack patients.
In the other study done on 1,900 patients who had suffered at least one heart attack that significantly weakened their heart's pumping capacity, Coreg reduced the chance of death from any source by 23%. It reduced the chance of a second heart attack by 41% within 15 months compared to patients who did not get the drug. In a second-study done on 2,289 heart -failure patients with severely weakened hearts, the death rate was reduced by 35% compared with the group given a placebo or standard treatment. Previous results for beta- blockers showed that beta-lockers reduced death rates in patients with mild to moderate heart failures.
Although we are not medical doctors we have been helped in connection with some of the technical details by a good friend or ours who is the head pharmacist at a leading New York area hospital.
On the other hand ACE inhibitors are much more costly than beta-blockers. The first of the ACE inhibitors are beginning to come off patent protection so that some generic ACE inhibitors are now being produced. Incidentally the diuretic pill costs about $1 apiece.
It has come to our attention that there is a generic version of beta-blockers that many physicians recommend which is just as effective as is the brand name version. We are not medical doctors so we certainly recommend that you consult your personal physician before acting on this matter. Specifically we are referring to Cappopril which costs about $10-20 per 100 for the typical 25-mg dose. Compare this cost to the brand name beta-blockers wherein the cost is about $100 per 100 for the typical 25-mg dose.
Both the American Heart Association and the American College of Cardiology have strongly recommended usage of beta-blockers for most first-time heart attack patients who are over 65 years of age. Dr. Harlan M. Krumholz, headed a research group at the Yale School of Medicine, that according to the Journal of the American Medical Association, concluded that beta blockers were being under prescribed for most first time heart-attack patients over 65 years of age. In December 1998 the AMA issued a "quality care alert" warning physicians that these potential life saving drugs were being underutilized.
The researchers examined the records of more than 115,000 patients 65 and older who were hospitalized for a heart attack in 1994 and 1995. According to their determination fewer than half the eligible candidates for the drugs received them when they left the hospital.
Beta-blockers decrease the amount of work your heart has to do and the amount of oxygen your heart needs. They inhibit the speed and force of two of the hormones that affect the heartbeat. About 10% of the patients taking beta-blockers feel tired or dizzy. See our article on Dizziness-Trying to Prevent Falls. Depression, diarrhea, or skin rash may be some of the other problems that ensue as a result of taking the medication. Dr. Krumholz's study found that 50% more of the patients in the 65-74-age category survived, who took the beta-blockers, than those who did not within a one-year period of time. The survival rate was almost 25% in the 74-85-age category.
There are many professionals who feel that taking aspirin is a more cost-effective methodology for survival. Research on patients with unstable angina has proven that taking an aspirin every day reduces the risk of heart attack or death. Tylenol and Advil do not have the same positive results as taking aspirin
Once again the cost question enters into the picture when examining beta-blockers and ACE inhibitors. Although beta-blockers are much older and less costly than ACE inhibitors many professionals prefer the ACE inhibitors. At the present time there is a substantial movement afoot to have prescription drug coverage for the elderly under Medicare. ACE inhibitors cost much more than beta-blockers. Are they worth the difference in cost? Should they be used in conjunction with each other instead of being used separately?
According to guidelines issued by the American College of Chest Physicians, that was published in the journal Chest, aspirin in combination with another blood thinning medication is more effective at preventing stroke and mini-stroke than aspirin alone. Previous studies had indicated that aspirin alone was helpful in preventing the reoccurrence of ischemic stroke, which occurs when a blood clot interrupts the flow of blood to the brain. The combination of aspirin and an extended release dipyridamole capsule, which is marketed under the name Aggrenox, was found to be very helpful in preventing the reoccurrence of strokes. Please see our article The Role of Aspirin and Heparin in Ischemic Stroke-Part IV
The latest data released from the study done on the results of Integrilin, which was given after angioplasty operations, has now become available. It indicates that it does significantly reduce the chance of death, another heart attack or need for a repeat procedure to reopen clogged coronary arteries for at least a 6-month period of time.
According to James E. Tcheng, a cardiologist at Duke University Medical College in North Carolina, the leader of the study group said the findings show the drug "provides a sustainable, long-term benefit" for patients undergoing the heart procedures. The study indicated that the drug reduced the risk of heart attack and death by 35% over that incurred by the placebo group. It lowered the occurrence of death, heart attack or need for a repeat heart procedure by 22% compared with the placebo group. Sales of Integrilin now exceed the sales of ReoPro, which is produced by Johnson and Johnson. Integrilin costs about $450 a patient while ReoPro costs about $1,350 a patient. The question that still has to be answered however is, will these figures hold up for longer than the 6-month period entailed in this study?
The August 13th, 1999 edition of the New England Journal of Medicine reported on the results of a study of the drug eptifibatide on patients with acute myocardial infarction (heart attack). The study was done under the leadership of Dr. Robert Harrington at the Duke University Medical College in North Carolina, and at Erasmus University in Rotterdam, the Netherlands. The study involved 10,948 patients in 28 different countries.
The drug was administered intravenously, along with aspirin and heparin. COR Therapeutics in conjunction with Schering-Plough announced the temporary halt of a study of their drug Integrilin + stents, which is the brand name for the drug. Their ESPIRIT study was halted because the analysis showed a nearly 50 % reduction in death/MI over 30 days vs. the placebo group. This compared very favorably with the Johnson and Johnson results in their EPISTENT trial in which ReoPro + stents showed a 51% reduction in death/MI. ReoPro is co-marketed byEli Lilly & Co and the Centocor division of Johnson and Johnson. New drugs are constantly coming on-stream in the attempt to find a better medication to help fight heart disease or heart failure.
A heart attack can occur as a result of an occlusive clot in one of the coronary arteries depriving oxygenated blood to heart muscles. This clot consists of a clump of small blood components, called platelets, held together by strands, known as fibrin. A stent is utilized after balloon angioplasty to help prop open the artery. The stent in particular has become an area where the clumping takes place.
The FDA had approved the drug Integrilin in 1998 for the treatment of unstable angina, the severe chest pains that often precede a heart attack, and for patients receiving balloon angioplasy. Integrilin works by blocking the receptor on the platelets responsible for the clumping, the platelet receptor GPIIb/IIIa. There were no increases in severe bleeding among patients on Integrilin vs. the placebo group. There are more than 700,000 angioplasty procedures done yearly in the U.S. The drug GPIIb/IIIa is an inhibitor that prevents platelet clumping and potential complete occlusion of coronary arteries.
Integrilin is priced at $365-$500 vs. ReoPro which is the leader in this market right now at $1,350. Eptifibatide is the generic that some doctors may prescribe to their patients in these cases. The results of a study headed by Maarten Simoons,a cardiologist at the University of Rotterdam, the Netherlands, concluded that ReoPro showed no benefit in reducing death or heart attacks among patients suffering from uncontrolled chest pain (unstable angina). The study did not question the results of the use of ReoPro or its competitors such as Integrilin in patients undergoing angioplasty and stent procedures to reopen blocked coronary arteries.
Merck & Co. had hoped that their anti-clotting agent Aggrastat would be able to best ReoPro in a study of 5,000 patients done at the Cleveland Clinic under the leadership of Eric J. Topol, chairman of the cardiology department. The results however showed that 7.6% of those given Aggrastat suffered a heart attack or other major adverse event within 30-days compared with 6% on ReoPro. Aggrastat is approved for use to treat some heart conditions, but isn't approved specifically for use in stent patients.
Sometimes a drug that looks promising in early trials fails to deliver in the long run. Such appears to be the case with Novarits AG's blood pressure drug Valsartan. In a study involving 5,010 patients using Valsartan against beta-blockers and ACE inhibitors the drug appeared to have little or no benefit for patients already using the other 2 drugs. Valsartan is one in a class of drugs known as angiotensin II receptor blockers, which work by obstructing the activity of angiotensin, a hormone that, among other things, causes blood vessels to constrict and raises blood pressure. The study was conducted at the University of Minnesota, under the leadership of Jay N. Cohn.
The Federal Drug Administration has approved a new drug to treat heart attack victims. The drug, Tenecteplase can be administered in one quick injection versus the 90 minutes that it takes to administer the clot dissolving protein tissue plasminogen activator (T.P.A.) which is known under the brand name as Activase.
The injection takes 5 seconds to administer, and it begins to work immediately to dissolve the clots that choke off the heart's blood supply. Genentech Inc., a subsidiary of Roche Holding Ltd., manufactures the drug, and is the same company that makes Activase. By dissolving the blockage it prevents further permanent damage to the coronary system. Tenecteplase will be sold under the brand name of TNKase. Activase costs about $2,200 per dose and the pricing for TNKase will be announced shortly.
A cloud has now arisen in connection with the administration of clot-busting drugs to heart attack victims over the age of 75 years. The results of the drugs known as thrombolytics were studied based on the analysis of medical records of 2,659 heart-attack patients in Minnesota hospitals. It was shown that 20.1 % of those over 75 who received the drugs died during their hospital stays, as opposed to 16.5% who did not receive the drug during their stays.
It was further determined that in the group that was considered perfect candidates for the drug, and who were administered the drug promptly, the risk of dying increased significantly with each year of age. A group headed by Stephen B. Soumerai, a researcher at Harvard Medical School, prepared the report. The results of a similar study done at Yale University Hospital should be announced shortly. It previously had been estimated based on some other studies that the risk of stroke after taking clot-busting drugs was about 2 to 2.5 % in people over 75 years of age, compared with 1 % in the rest of the population. The American Heart Association and the American College of Cardiology recommend that people of all ages get clot-busters as soon after a heart attack as possible.
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 April 7, 2004
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