Aspirin as a Preventative Therapy against Cardiovascular Events
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. There you will find "Risk Assessment Tool".
(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.
(4/13/07)- Studies done on male subjects have shown that taking one baby aspirin a day is an excellent preventative for them from having heart attacks. The evidence of this happening with women is however in conflict.
A few years ago, the Women's Health Study of 40,000 women found that taking aspirin on a daily basis had no appreciable effect in decreasing the risk of heart attack for women 45 and older. On the other hand Harvard researchers recently reported that women in the university's Nurses Health Study who used aspirin regularly had a 39% lower risk of heart attack, and a 12% lower risk of getting cancer.
There were over 80,000 women who participated in the Harvard Nurses Health Study. Some medical professionals point out that it is likely that the nurses in this study were more health conscious than ordinary women would be, so that this may account for the difference between the two studies.
It is estimated that there is about a 70% greater risk of having gastrointestinal bleeding from daily ingestion of aspirins, so there is a risk factor in using aspirin whether you are a male or a female. There is also an increased risk of hemorrhagic stroke when an individual takes aspirin on a regular basis.
(5/01/06)- Harvard Medical School associate professor Daniel Simon, who has been a vocal proponent of the "aspirin resistant" effect will be beginning a study of this area under a $2 million study grant funded by Accumetrics and Schering-Plough. The study expects to enroll about 600 patients to determine if patients about to undergo angioplasty are resistant to aspirin or Plavix. (please see our item dated 3/21/06).
The Accumetrics test, which is covered by Medicare and most insurers costs the doctors and most hospitals about $20-$22. Medicare reimburses $30 for the test. The exact extent of "aspirin resistance" is unknown, but because of the fact that many of the drug companies with vested interests in discouraging the usage of aspirins, the media has been increasingly inundated with such claims..
The American Heart Association recommends that those who have suffered a stroke or heart attack take one aspirin a day, based on studies showing this regimen can reduce heart attacks and strokes by about 25%. To limit potential damage to the stomach, most doctors recommend that individuals taking aspirin on a daily basis limit it to 81-mgs a day, which is what is normally the dosage in a baby aspirin.
(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.
(8/30/05)- Researchers at Massachusetts General Hospital, Brigham and Women's Hospital and Harvard Medical School, all in Boston found that women who took high-doses of aspirin or certain anti-inflammatory painkillers such as ibuprofen on a regular basis for more than 10 years cut their risk of colon cancer.
According to the lead researcher for the study, Andrew T. Chan, a physician in the gastrointestinal unit of Massachusetts General Hospital and an instructor at the Harvard Medical School warned that the risk of gastrointestinal bleeding also increased as the dose of aspirin and NSAIDs increased. He said that for every one or two cases that aspirin might prevent that it could cause eight serious bleeding events.
Patients who usually take aspirins to prevent cardiovascular events usually take baby aspirin or about 80-mgs a day. Low doses of aspirin were not shown to significantly decrease the chance of colon cancer even when taken over long periods of time.
The study included 82,911 women in the Nurses' Health Study that started in 1980. Researchers studied the 20-year period from 1980 to 2000. 862 women in the study group developed colon cancer over that period of time. The study concluded that by taking 14 or more aspirins a week a woman could decrease her risk of colon cancer by 53% if they took that dosage over a 10 year period of time.
(7/11/05)- The results of a study of nearly 40,000 women concluded that they did not decrease their chances of getting lymphoma, colorectal or breast cancer, although results for lung cancer were less conclusive by taking aspirin. The study called the Women's Health Study was partially funded by the National Cancer Institute. Julie Buring of Harvard's Brigham and Women's Hospital was the lead researcher of the study whose results appeared in the latest issue of the Journal of the American Medical Association.
The women who took part in the 10-year study used doses a little higher than in baby aspirin, taken every other day and compared against placebo pills.
The results of a study of 70,144 men over a nine- year period of time concluded that aspirin was beneficial in reducing the risk of prostate cancer. The results of this study appeared in the recent edition of the Journal of the National Cancer Institute. The researchers in this study asked the men about their use of aspirin and other non-steroidal anti-inflammatory drugs, including ibuprofen, such as Advil and Motrin. Men who took standard 325-mg doses of those medicines daily for at least five years were about 18% less likely to get prostate cancer then men who used aspirin occasionally for a shorter duration.
(3/19/05)- A major 10-year study that was funded by the NIH suggests that aspirin affect men and women differently when it comes to preventing first heart attacks and strokes. The study involved nearly 40,000 women aged 45 and older. It suggests that a regular every-other-day regimen of low dose aspirin was effective in preventing a first stroke in women, but had no effect in helping avoid a first heart attack. The women in the study had no history of cardiovascular disease.
This is the exact opposite in regards to men as determined in previous studies. In those studies it was suggested that aspirin where low-dosages of aspirin helped to prevent a first heart attack, but if anything, it may slightly increase the risk of strokes. The result of the landmark study for men was published in 1989, and has pretty much been the gospel since then.
For healthy women younger than 65, the benefits of taking aspirin regularly are limited. It is important that each individual, male or female, discuss this matter with their own physician before deciding whether or not to embark on an aspirin regimen. It is well recognized that whether you are male or female, aspirin reduces your risk of subsequent risk of cardiovascular disease.
According to data from the American Heart Association, it was estimated that 345,000 women had heart attacks in 2002, while 373,000 of them suffered a stroke in that year. For men in 2002, 520,000 had heart attacks and 327,000 suffered strokes in 2002.
The U.S. Preventive Services Task recommends routine low-dose aspirin for adults (male or female), whose risk of having a heart attack over the next 10 years is 6%-based on such risk factors as age, cholesterol levels, smoking status and blood pressure.
(1/8/05)-An estimated 17,000 people die each year due to gastrointestinal complications from non-steroidal anti-inflammatory drugs such as naproxin. "Enteric coated" aspirins are meant to deal with this problem. Enteric coated aspirins have coating that permits the pill to move through the stomach to the small intestine before the medication is released.
Enteric coated aspirins relieve but do not eliminate entirely the gastrointestinal risk. A study published in the April 1994 Journal of Rheumatology followed 350 patients with osteoarthritis or rheumatoid arthritis who had stopped using pain relievers within the past year because of gastrointestinal complaints. The study showed that 16% of patients using the enteric-coated aspirins developed gastrointestinal problems compared with 25% in the standard naproxen group. Both medications worked equally in relieving the pain symptoms.
Enteric-coated aspirins costs about $1.22 per tablet versus the cost of about 28 cents a pill for the naproxen. Your doctor can provide a prescription for enteric-coated pills, but please keep in mind that many FSA plans cover over-the-counter medications as well as prescription drugs. A small Irish study found that enteric-coated aspirins do not prevent platelets from clumping as well as low-dosage aspirin. "All aspirin appears to be beneficial whether it's enteric-coated or not," says William Frishman, chief of medicine at Westchester Medical Center in Valhalla, N.Y.
(10/22/04)-The benefits of taking aspirin may not help everyone. New evidence shows that up to 25% of the population are aspirin resistant. Since it is estimated that over 20 million Americans take aspirin to prevent heart attacks or strokes, this means that a substantial percentage of the users are non-responsive to the medicine. Recently it has been determined that aspirin takers who are resistant have a higher rate of heart attacks and strokes than do nonresistant aspirin users.
New tests have evolved that can determine who is resistant to aspirin consumption. The standard test of how readily platelets clump is called aggregometry. It is both an expensive and time consuming test, since the test itself used to take between two to three hours to administer. A lab needed to be used to determine the results. Doctors who determine that their patients are resistant to aspirin have been recommending Plavix as a substitute for aspirin. Plavix, know generically as clopidogrel, is jointly marketed by Bristol-Myers Squibb and Sanofi-Synthelabo. Plavix costs about $3 a pill, so there is a big cost differential between it and aspirin.
Scientists have been unable to determine why some people are resistant to aspirin, but hopefully this question will be answered shortly.
New tests have recently come to play in this area, and they are cheaper and much less time consuming. Accumetrics, a small company in San Diego received clearance from the FDA at the end of 2003 for its VerifyNow test. This test can be performed in the doctor's office and the results are ready within minutes. The tests range in price from $30 for VerifyNow to $100 for some of the newer tests that are on the market.
The results of a recent research study showed that women who are prone to hormone sensitive breast cancer could benefit from taking aspirins. The hormone estrogen stimulates about 60% to 70% of all cases of breast tumors. Breast cancer is the most common type of cancer in women, with 215,990 cases and 40,110 deaths expected this year from the disease.
Women who took aspirin 7 or more times a week had a 26% lower risk of developing those tumors than women who did not take it, according to the results of the study done under the leadership of Mary Beth Terry. Dr. Terry is an assistant professor of epidemiology at the Mailman School of Public Health at Columbia University.
For women not already taking aspirin, Dr. Terry said "the only fair thing would be to have the woman take it or not based on what her physician recommends given her overall health profile." More research must be reported on however before it can be unequivocally stated that aspirin can be used as a preventative against hormone type breast cancers.
Researchers at the University of North Carolina and the Mount Sinai School of Medicine in New York also participated in the study. Dr. Andrew J. Dannenberg, an author of the study and the director of cancer prevention at the Weill Cornell Medical College in Manhattan concurred in the thought that eventually aspirin may be recommended in preventing the recurrence of breast cancer in women who have had breast cancer.
The study included 1,442 women with all forms of breast cancer and 1,420 without the disease. Among the women with cancer 301, or 20.9% had taken aspirin at least once a week for six month or longer. Of the health women, 345, or 24.3% had taken aspirin. The suggestive protective effect showed only an association and did not prove cause and effect.
Recently, The US Prevention Service Task Force (USPSTF), a group of private-sector experts on prevention and primary care issued new recommendations about the benefits of aspirin as a preventative therapy. It had been known that aspirin is a preventative benefit to protect against second incidence of cardiovascular disorders, following the first occurrence. In fact, many cardiologists view aspirin as the backbone of preventative cardiology as well as treatment after coronary syndromes. They indicate that aspirin’s protective benefit increases as cardiovascular risk increases.
In order to come up with their recommendations, The USPSTF reviewed various studies, which were recognized as scientifically sound, involved randomized trials, lasted more than a year, and in which individuals were without cardiovascular disease. These studies showed that aspirin reduced coronary heart disease by 28% in patients without cardiovascular disease.
This meta-analysis also determined that aspirin could benefit any patient at increased risk of cardiovascular events-defined as a >3% risk of experiencing coronary heart disease events (primarily heart attacks) over the next 5 years. The chief investigator, Dr. Pignone, assistant professor of medicine, University of North Carolina, Chapel Hill indicated that these recommendations are based on quantifying, rather than estimating, cardiac risk. The method to quantify this risk can be found on the Internet at www.med-decisions.com. The risk factors that increase the chances of a cardiac event include hypertension, diabetes, hypercholesterolemia, and family history of cardiac events and smoking.
Recently there have been several studies that show that daily use of aspirin cut the risk of a heart attack by an average of 28% for those who did not have a prior heart attack. Although aspirin does increase the risk of internal bleeding, it has not been shown that it helps prevent ischemic strokes, which occur when a clot cuts off blood flow to the brain.
For people who have a low risk of having a heart attack, the risks associated with aspirin ingestion exceed the benefits afforded by taking the drug. The Internet has several sites that help you evaluate your 10-year risk of having a heart attack. Some of the sites are:
www.nhlbi.nih.gov/guidelines/cholesterol/index.htm and www.med-decisions.com .
The calculators will ask your age, blood pressure and cholesterol levels among other things. The U.S.Preventive Services Task Force recommends that the benefits outweigh the negatives for those whoes 10-year risk is at least 6%. Like everything else in this world not every one will benefit from aspirins. Doctors at the Cleveland Clinic found that 9% of the patients that they tested appeared "resistant" or that their blood did not have the usual blood thinning effects associated with taking aspirin.
Most of the studies that have been done on the effect of aspirin involved middle aged men, so it is only recently that studies have begun to show what effect taking aspirin will have on the female population.
The 75 to 81 mg dosage of aspirin that the task force recommends is considered a low dose. For those individuals at less than 3% probability of a five-year risk of experiencing a cardiac event, aspirin best be avoided because of adverse reactions including GI bleeding or hemorrhagic stroke.
Some researchers indicate that enteric-coated aspirin at 325-mg dosages may have a more robust effect than the 75-81 ordinary aspirin. One such researcher is Feng and his group who studied forty healthy male subjects in a randomized, double blind, parallel study design. They looked at platelet inhibitory and prostacycline-sparing effects of the two doses of aspirin-81mg of ordinary aspirin and 325 mg of enteric-coated aspirin.
They found that 325-mg enteric-coated aspirin inhibited collagen induced aggregation to a greater degree than 81-mg dose. They concluded "that this additional platelet inhibitory power may have significant clinical relevance in situations such as acute coronary syndrome (e.g., acute myocardial infarction and unstable angina) which are mediated by plaque rupture and involve significant collagen exposure and subsequent platelet activation and aggregation." (See: Feng D L, McKenna C, Murillo J et al. Effect of Aspirin Dosage and Enteric Coating Platelet Reactivity. Am J. Cardiol 1997; 80:189-193). The study also showed that enteric-coated aspirin provides better prostacycline-sparing effects than the lower dose aspirin. Prostacycline is known to be a vasodilator and inhibitor of platelet aggregation.
Dr. Tobias Kurth led a study done at the Harvard Medical School and the Brigham and Women's Hospital in Boston that concluded that the taking of other painkillers on a steady basis along with the ingestion of aspirin inhibited the protective anti-heart attack benefit of taking the aspirin alone. "However, if you took them intermittently or casually, you were not effected," said Dr. Kurth. Aspirin has an anti-coagulant effect and that is one of the reasons given for its benefit in preventing heart attacks.
Aspirin, ibuprofen, naproxen and other similar drugs are called non-specific anti-inflammatory drugs. They work by interfering with two enzymes called Cox-1 and Cox-2. Ibuprofen turns off Cox-1 temporarily, making it safer than aspirin, but it seems to compete with aspirin when the two are regularly taken together. Taking a dose of aspirin daily has been shown to reduce the risk of a heart attack by about 44%.
"What this shows is that it's hard to beat aspirin," said lead researcher Philip Gorelick of Rush-Presbyterian-St. Luke's Medical Center in Chicago in discussing the results of a study he lead which compared aspirin to ticlopidine in trying to prevent strokes among blacks. The research involved 1,809 black men and women who took aspirin or ticlopidine for as much as two years.
As a matter of facts the study showed that aspirin was even better than the ticlopidine in preventing strokes. A month's supply of aspirin costs about $10, while and equivalent supply of ticlopidine costs about $100. An estimated 700,000 Americans suffer strokes each year. Blacks have about double the risk of strokes than do whites. Ticlopidine is sold under the brand name of Ticlid and it was approved in 1991 to treat strokes for patients who can not be given aspirin. Roche Laboratories, a division of Roche Holding AG of Switzerland makes the drug.
After angioplasty, a patient is subjected to a wide assortment of different medications. These include aspirin to prevent clots, an ACE inhibitor to regulate blood pressure, and a statin to lower cholesterol levels. Patients who have suffered a heart attack are also usually advised to take beta-blockers as well as these other medications.
According to Steven R.Steinhubl, a cardiologist and researcher at the University of North Carolina at Chapel Hill, who led a study on the effects of the super aspirin Plavex after angioplasty, this one medication may be enough to do the job by itself.
Bristol-Myers Squibb Co. and Sanofi-Synthelabo of France, co-market Plavex (clopidogrel), which currently has over $1 billion in sales. According to the study patients who take the drug for one year after undergoing angioplasty have a 27% less chance of dying or suffering a heart attack or stroke. The study involved 2,116 patients of whom about 85% had stents implanted as part of the angioplasty procedure. The researchers found that one-year after the procedure, 8.5% of the patients who were given Plavex suffered a heart attack, stroke or died versus the 11.5% of the control group. On the down side of the study, more of the Plavex patients did suffer a severe bleeding episode compared to the control group.
Dr. Dennis T. Mangano founder of the Ischemia Research and Education Foundation of San Francisco wrote up the results of a study paid for by the foundation, that involved giving aspirin to patients within 48 hours after they had heart surgery. The patients in the study were treated at 70 hospitals in 17 countries from 1996 to 2000. The study concluded that giving heart bypass patients aspirin within 48 hours after having heart bypass surgery greatly reduced their risk of death and serious complications involving the heart, brain, kidneys and digestive tract.
Over 355,000 Americans had heart bypass surgery in 1999, the last year for which the figure is available. Many doctors fear giving aspirin to bypass patients because aspirin does increase the risk of internal bleeding. According to the study, the death rate of patients who were given aspirin within 48-hours after bypass surgery was only 1.4%. For those not given aspirin within 48-hours, the death rate was 4%.
The patients in Dr. Mangano's study were not picked at random in regard to who would and who would not receive the aspirin. Thus a randomized controlled study will have to be undertaken to confirm these results.
An advisory panel of the FDA concluded its hearings in regards to the labels on common painkillers such as acetaminophens, ibuprofen, naproxen and aspirins. As a result of these hearings the advisory panel will recommend to the FDA that stronger warning labels are needed for these painkillers. The FDA is expected to act on these recommendations early in 2004. The panel did not question the safety of these products when taken as directed, but questions have arisen in connection with misreading of the labels and overuse of these products.
The panel found evidence that thousands of Americans unwittingly take toxic doses of acetaminophen, which is the main ingredient in almost 200 over-the-counter cold and headache remedies, including Tylenol. The panel voted 23-1 in favor of recommending to the FDA that stronger warnings be required on the labels of all acetoaminophens. Acetaminophen is also found in painkillers such as Percocet and Vicodin.
The panel recommended that every package of a drug that contains acetaminophen states in bold type on the label that it contained the ingredient. It also recommended that the label state in bold letters that taking more than the recommended dosage could result in liver damage. Johnson & Johnson has already undertaken this steps in connection with the labels on Tylenol.
The panel also stated that certain groups of patients, such as the elderly should be warned that they risk stomach bleeding or kidney failure by taking the class of medicines known as nonsteroidal anti-inflammatory drugs known as NSAIDs. Included in the NSAID category are aspirin, ibuprofen, found in Motrin and Advil, and naproxen found in Aleve.
Researchers have noted that acetaminophens (Johnson & Johnson's Tylenol is the best known of these products) can cause liver problems over time, and aspirins can cause gastrointestinal bleeding with prolonged use. John Jenkins, head of the FDA's Office of New Drugs stated that "We'd like to do a better job of preventing some of these (adverse effects)." The advisory panel's recommendation is usually upheld by the final decision of the FDA.
In an interesting side-note to the panel's hearing, each product side in the debate is emphasizing the weakness of the other side, while minimizing the weak points of their own drug. An FDA review of acetaminophen overdoses found that consumer calls to poison-control centers about acetaminophens decreased from 111,175 in 1995 to 108,102 in 1999. Deaths however associated with the drug's overdose rose from 76 to 141 in the same period. The number of deaths included death from suicide as well as from accidental overuse.
It is almost a given that the geriatric population has some cardiovascular risk. Cardiovascular disease resulted in 958,775 deaths in the United States in 1999. This total represented 40.1% of all deaths or to put it another way, one out of every 2.5 deaths were the result of cardiovascular disease. The number of women who died was greater than the number of men, reflecting that a larger proportion of women than men are living into the oldest age range.
It is a good idea to talk with your primary care physician before you start any regimen of aspirin. You want to optimize the outcome of use of aspirin and minimize the risks. Please also see our article Colon Cancer in regards to some interesting study results in connection with the usage of aspirin and its possible effect in reducing the risk of colon cancer.
Please also see our article: The Role of Aspirin in Ischemic Stroke-Part V
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "How to Select a Nursing Home"
Allan Rubin and Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated February 16, 2008
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