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Posts Tagged ‘aspirin’

High-dose aspirin for migraines

Posted by medconsumers on April 14, 2010

This is the most satisfying pharmaceutical research story to report: A cheap non-prescription drug—aspirin—has been shown to be almost as good as the popular, high-priced prescription drug. People who suffer migraine headaches usually take the prescription drug Imitrex, which is expensive even when purchased in its generic form (sumatriptan). Nearly the same degree of relief, however, can be received from a single high dose of aspirin (1,000 mg)…and with fewer adverse effects. The aspirin vs placebo and the aspirin vs Imitrex studies are part of a new review from the Cochrane Collaboration. It is based on 13 studies with a combined total of 4,222 participants.

More than half of the people who took high-dose aspirin experienced pain relief within two hours of taking high-dose aspirin. And many said that it lasted 24 hours. One in four went from “moderate or severe pain” to “no pain” within two hours after a single 1,000 mg aspirin dose. And one in two said their pain went down to “pain no worse than mild pain.” High-dose aspirin also reduced the nausea and vomiting experienced during a migraine headache. These findings came from trials that had randomly assigned people to take high-dose aspirin or a placebo as soon as the migraine began. The addition of a 50 mg dose of the gut-protecting prescription drug called Reglan (generic name: metoclopramide) reduced the nausea and vomiting symptoms, though it had no effect on pain relief; a 100-mg dose was only slightly better at alleviating pain within two hours.

Then there are the studies that compared people taking an oral dose of Imitrex (100 mg) plus Reglan with people taking high-dose aspirin with or without Reglan. Imitrex had a small advantage over aspirin in terms of more pain relief at two hours. Adverse reactions to high-dose aspirin were not an issue, but adverse effects occurred slightly more often in people taking Imitrex.

This Cochrane review, entitled “Aspirin with or without an anti-emetic for acute migraine in adults” was conducted by Varo Kirthi and colleagues at the University of Oxford, U.K.

For more information:

Migraine drugs are usually taken on a short-term basis but be aware that chronic use of Reglan can have severe adverse effects. Last year, the FDA ordered a “black box” warning for Reglan’s label (click here for an example of a drug label). Chronic use should be avoided because it can cause a movement disorder called tardive dyskinesia, which is more likely to occur in the elderly, especially elderly women. Tardive dyskinesia is described as involuntary, repetitive movements of the extremities, lip smacking, grimacing, tongue protrusion, etc. It is rarely reversible, according to the label, and there is no treatment.

Why it is so common to learn of a new adverse effects long after a drug received FDA approval was explained in a recent commentary entitled, “The missing voice of patients in drug-safety reporting” for The New England Journal of Medicine (click here). During the clinical trials required by the FDA for new drug approval, the study participants are not asked about symptoms they have while taking a drug. Incredibly, the side effects reported in these trials are based on the physicians’ and nurses’ impressions of the trial participants’ adverse drug reactions.  These impressions become the initial source of side effect warnings in the FDA-approved drug label. This New England Journal of Medicine commentary cites “a substantial body of evidence,” showing that physicians “systematically downgrade the severity of patients’ symptoms” and that “patients’ self-reports capture side effects that physicians miss.”

Maryann Napoli, Center for Medical Consumers(c)ISSN 2155-1480

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Painkiller’s Ads Hype New Combo of Old Drugs

Posted by medconsumers on February 1, 2006

Combunox:

Combunox is advertised by Forest Pharmaceuticals as though it were a new drug. Actually, it is a combination of two old drugs: the semi-synthetic opioid prescription drug, oxycodone, plus the popular over-the-counter anti-inflammatory painkiller, ibuprofen. The combination supposedly provides an extra punch. But The Medical Letter (1/2/06), a physician publication without drug advertising, assessed the studies supporting the use of this fixed combination drug and concluded that people with acute pain might be better off taking ibuprofen alone.

At a dose of 400 mg (the amount in Combunox), ibuprofen is doing the lion’s share of the painkilling. “A 400-mg dose of ibuprofen is generally superior to 1000 mg dose of acetaminophen (brand name: Tylenol) and is comparable to acetaminophen/codeine combinations,” according to The Medical Letter. “The analgesic effect of ibuprofen does not increase with doses greater than 400 mg; the anti-inflammatory effect does and so does the drug’s gastrointestinal toxicity.”

Who were the study participants?

In one clinical trial, Combunox was better than a placebo in women with moderate to severe pain 14 to 48 hours after abdominal or pelvic surgery, and in another trial that involved people who have had dental surgery.

What’s New About Combunox?

Not much. Oxycodone was introduced over 50 years ago and reintroduced in the ensuing years under numerous brand names (including OxyContin and Percolone) and in combination with over-the-counter painkillers, such as aspirin/oxycodone (Percodan) and acetaminophen/oxycodone (Percocet). Combunox represents the first time oxycodone has been combined with ibuprofen.

Cautions

Combunox is approved for the short-term (seven days) treatment for moderate to severe acute pain because prolonged use can lead to dependence. The warning is based on longstanding concerns about oxycodone. As with all opioids, abuse is a strong possibility. Under its most popular brand name OxyContin, oxycodone has received considerable media attention because of continuing reports of abuse. One risk of taking a fixed combination, according to The Medical Letter is this: Dependence upon oxycodone may cause people to increase the dose, which in turn could lead to overdosage of ibuprofen.

Alternatives

A week’s supply of Combunox costs $10.08 to $40.32, says The Medical Letter, whereas, the same amounts of generic ibuprofen and oxycodone would cost $4.80 to $19.20. The Medical Letter findings suggest that 400 mg of ibuprofen alone might be the safest choice.

Maryann Napoli, Center for Medical Consumers ©
February 2006

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Do Cholesterol-Lowering Drugs Benefit Women?

Posted by medconsumers on June 1, 2004

Many doctors have come to believe that the cholesterol-lowering drugs called statins (Lipitor, Zocor, Pravachol, Mevacor, Crestor) are safer than low-dose daily aspirin. That becomes apparent whenever statins are featured in the media as a wonder drug for the prevention of heart disease. In fact, there’s a growing consensus among cardiologists that all adults should take a statin whether or not they are at high risk.

Yet women have been underrepresented in the major clinical trials in which people with and without heart disease were randomly assigned to take a statin or a placebo (dummy pill) every day for several years. Women made up less than one-third of all the study participants. Put that together with the fact that women under the age of 75 years have a low rate of heart attack and stroke. Add this disturbing bit of news from University of British Columbia researchers who conducted a thorough review of the five prevention clinical trials: only two of the five trials released their data regarding the serious adverse effects* suffered by the study participants who were taking statins. Working with what they had, that is, the data from only two of the statin trials, the researchers found that statins did not prolong life for men or women. Worse, the benefit of taking statins (a reduced rate of non-fatal heart attacks and stroke) was offset by an increase in the serious adverse events. Until all the statin trials release their serious adverse effects data, the public will not know whether these drugs are safer than low-dose aspirin.

The sparse information that people receive about cholesterol treatment was unintentionally but aptly illustrated recently by one of the country’s top medical journals. The Journal of the American Medical Association, or JAMA, regularly publishes a “patient page,” which amounts to a layman’s translation of one of the more important papers published in each issue.

The May 12, 2004 issue of JAMA contained a review of all trials in which women with high cholesterol had been randomly assigned to take a drug or a placebo. (Most of the trials involved a statin.) Judith M.E. Walsh, MD, MPH, and Michael Pignone , MD, MPH conducted the review. Their conclusion: For women without heart disease, drugs did not prolong life or reduce the odds of dying of heart disease. The drug may reduce non-fatal cardiac events (heart attack, stroke, etc.), but “current evidence is insufficient to determine this conclusively.” For women with heart disease, drugs do not affect mortality but will reduce non-fatal events.

Turn to the patient page in the same issue of JAMA, and none of this important information can be found. Instead, six sentences are devoted to statins explaining how they work; the need for regular lab tests to check for statin-induced liver damage; the possibility of muscle damage, etc. The reader will find nothing about the drugs’ effectiveness (or ineffectiveness) in preventing or treating heart disease. The rest of the page was given over to the usual information about exercise and smoking cessation. Worse, it has outdated information about the importance of a low-fat diet; despite the fact that a review of all relevant studies found that it has little effect on heart disease prevention (see below). The patient page is intended for physicians to photocopy and give to their patients.

And what about the unreported serious adverse effects of statin drugs? Not a mention in the patient page, of course, but there it was in the “comments” section of the JAMA article. At the end of their review, Drs. Walsh and Pignone discuss possible explanations for why statins do not prolong life for women with heart disease. The drugs reduce the odds of dying of heart disease, but that benefit is canceled by a higher rate of death from other causes.

“Possible explanations include chance, the limitation that not all studies reported both heart disease and total mortality… Another potential explanation might be an increase in a competing cause of mortality, for example, an increase in hemorrhagic stroke with cholesterol-lowering therapy. However, information on the causes of non-heart disease mortality is not available for all the trials, so this possibility cannot be proven. [emphasis added] Publication of cause-specific mortality for many of the larger trials could help to clarify the association between cholesterol-lowering therapy and total mortality.”

There you have it, the full story is not yet available on the safety of cholesterol-lowering drugs, though these trials were published years ago. Traditionally, researchers design trials to answer specific questions. In this case: Does this drug reduce the rate of heart attacks and strokes or the rate of cardiovascular death? But the drug itself might cause deaths from other causes, and as Drs. Walsh and Pignone wrote, not all studies reported deaths from other causes. These concerns are relevant to men, as well.

As for the doctors who say that statins are safer than aspirin, they might one day be proven correct. But it took more than 100 years to get the full story on aspirin. (In fact, there might be more to learn.) Gastrointestinal bleeding and rarely, hemorrhagic stroke are both potentially fatal side effects of chronic use of aspirin, even at low doses. And the dangers of giving aspirin to children who have flu or chicken pox have only been known to be associated with the rare risk of Reye’s syndrome for less than 30 years.

For More Information:

- Go to the Web site, sponsored by the above-mentioned University of British Columbia researchers (www.ti.ubc.ca). In the archives, locate Therapeutics Letter No. 48 “Do statins have a role in primary prevention?

- Go to the archives of the British Medical Journal at www.bmj.com for the review of all studies assessing the heart disease prevention benefit of reduced dietary fat intake. Find the March 31, 2001 issue featuring “Dietary fat intake and prevention of cardiovascular disease: systematic review” by Lee Hooper et al.

*Serious adverse effects are any untoward medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, or results in persistent or significant liability.

Maryann Napoli, Center for Medical Consumers (C)
June 2004

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Second Thoughts about Aspirin a Day to Prevent Heart Attacks

Posted by medconsumers on January 1, 2004

A baby aspirin a day keeps a heart attack away. This widely accepted health practice was seriously undermined at an advisory committee meeting of the Food and Drug Administration (FDA, held in December 2003. The FDA advisory committee voted overwhelmingly to reject a petition from the Bayer Corp. to approve aspirin for reducing the risk of a first heart attack.

Though an estimated 20 million Americans already take low-dose aspirin daily to prevent a heart attack, this is an off-label use—that is, the aspirin manufacturers have not received FDA approval for this particular indication. FDA approval is required, however, once an aspirin manufacturer plans to advertise the drug for this use. And once approval is granted, the drug’s packet insert must be rewritten to inform consumers of the new indication.

Bayer’s petition made the FDA Cardiovascular and Renal Drugs Advisory Committee take a critical look at the five trials (One trial compared aspirin with vitamin E) in which people without heart disease took either aspirin or a placebo (a dummy pill). Altogether there were more than 55,000 participants at anywhere from low to high risk for a heart attack. Here is what the cardiologists and other experts on the committee found in the way of benefit: Aspirin produced about a 32% reduction in non-fatal heart attacks. [Translation: An estimated 3% of all moderate-risk people will have a heart attack in the next five years. Daily low-dose aspirin therapy will reduce their odds to about 2%.] The benefit is given in terms of a five-year period because the trials lasted four to seven years.

Several things troubled the FDA committee members about the results of these trials: Aspirin did not have any mortality reduction benefit; nor did it reduce the odds of having an ischemic stroke, which is, arguably, the most feared consequence of heart disease. Yet aspirin has the potential for causing another, less common type of stroke called hemorrhagic stroke, which is a rupture of a blood vessel in the brain.

One committee member who voted to reject Bayer’s petition is Steven Nissen, MD, Medical Director of the Cleveland Clinic Cardiovascular Coordinating Center. In a telephone interview, Dr. Nissen explained, “The data [from the five trials] were terribly weak.” You always have to weigh the trade- offs , he said, referring to hemorrhagic stroke as the major concern.

But the aforementioned 32% reduction in non-fatal heart attacks applies to the combined total of all the study participants, most of whom were men with differing levels of risk. The committee hit a snag once it came to individuals. Dr. Nissen said that he and other committee members were concerned that daily aspirin, if taken by people at a low enough risk, could cause more harm than good. Asked to define “low enough risk,” he explained that there was too much uncertainty to answer the question. “No one in the world can answer the question of who benefits and who doesn’t, and if there is no answer, then how could I vote to approve?” he asked.

The fact that women were underrepresented in the five trials (only 20% of all participants) also troubled Dr. Nissen. “It may be that the risks exceed the benefit for women,” he said, “but we simply don’t know—there is not enough data.” Still, Dr. Nissen was careful to stress that he was not against aspirin therapy for everyone, suggesting that people talk over the decision with their physicians. The FDA advisory committee “took a lot of heat,” said Dr. Nissen, referring to its decision to turn down Bayer’s petition and thus reject the prevailing medical view that aspirin therapy is good for just about everyone. “We were called flat earthers ,” he said.

The FDA is not obligated to follow the decisions made by its advisory committees, but the agency usually does. The committee’s decision, though entirely appropriate, illustrates how the current system works against consumers who want to become fully informed before they go on lifelong drug therapy. Approval would have meant a rewrite of the drug’s packet insert to include the new indication. And this, in turn, would have compelled the advisory committee to identify the appropriate group of people for whom the benefit of aspirin therapy clearly outweighs the risks. The evidence from the five trials did not provide the answer; therefore, 20 million people will continue to take daily aspirin without knowing anything about the uncertainties of the supporting research.

The advisory committee’s concerns can be contrasted with the practice guidelines aimed at physicians and published in 2002 by the U.S. Preventive Services Task Force. The Task Force concluded that the number of “cardiac events” prevented by aspirin therapy far exceeded the number of hemorrhagic strokes caused by aspirin therapy. This, too, is based on the combined results of the same five trials. When the Task Force tried to break things down for individuals, it came up with this estimation for moderate-risk men and women: “For 1,000 patients with a 3% risk of having a heart attack in the next five years, aspirin would prevent eight heart attacks but would cause one hemorrhagic stroke and three major gastrointestinal bleeding events.”

Where it concerns low-risk people, the Task Force is in agreement with the FDA advisory committee: MMMM
“…patients at low risk for coronary heart disease probably do not benefit from and may even be harmed by aspirin because the risk for adverse events may exceed the benefits…” (Annals of Internal Medicine, 1/15/02).

For More Information:

  • Go to www.med-decisions.com to see one method used by the Task Force to identify different levels of risk for a heart attack. The Task Force used an additional assessment tool based on the risk information from the Framingham Heart Study, which has since become outdated.
  • The transcript of the December 8-9, 2003 meeting of the Cardiovascular and Renal Drugs Advisory Committee is likely to be posted on the Internet in February or March. Go to www.fda.gov and click into “Advisory Committees.” Then go to this specific committee and its meeting date.

Maryann Napoli
January 2004

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C-Reactive Protein Testing For Heart Disease

Posted by medconsumers on December 22, 2002

Should You Be Tested For C-Reactive Protein?
By Maryann Napoli

The revised view of heart disease got a boost recently. Over the last ten years, a research case has been building for the possibility that chronic inflammation within the coronary artery walls plays a strong role in the development of heart disease. This hypothesis received some support from a new study showing that inflammation is a better predictor of who will have a heart attack than high cholesterol (The New England Journal of Medicine, 11/14/02). Nearly 28,000 healthy women were tested and followed for eight years; those whose blood tests showed high levels of C-reactive protein (CRP), an indicator of inflammation, were twice as likely to have a heart attack or a stroke as the women with high levels of LDL cholesterol, also known as the “bad cholesterol.” Similar findings are showing up in an ongoing study of 22,000 men.

Media reporting of this study generally gave the impression that many doctors did not think people should seek CRP testing, though it is readily available. And the leading guidelines-setting organizations like the American Heart Association have yet to take an official position about whether the CRP test should become part of the standard battery of tests routinely administered to all adults. But a New York Times editorial was downright enthusiastic, “The test could be a boon, if not for every American then at least for all those whose weight, age, smoking or other factors make them wonder about their cardiovascular prospects.”

It would be premature to start screening all adults for CRP, according to Lori Mosca, MD, who is the Director of Preventive Cardiology at New York Presbyterian Hospital. “We don’t yet know how to use this information, even though we do know that statistically CRP has been shown to predict cardiovascular events-just like 300 other risk markers for heart disease.” Dr. Mosca wrote the editorial that accompanied the new study, entitled, C-Reactive Protein-to Screen or Not to Screen? “People are calling my office to ask, ‘should I have a stress test or an angiogram’ because their CRP is elevated. I think there’s a real risk that this information is going to be misused,” she warned in a telephone interview. “And until science can figure what to do with the information, I think that screening every American is not appropriate at this point.” What’s more, gingivitis, bronchitis and many other possibilities can raise CRP levels.

That view was seconded by David Atkins, MD, chief medical officer at the Center for Practice and Technology Assessment at the U.S. Agency for Heathcare Research & Quality. To Dr. Atkins, the known major risk factors for heart disease-high blood pressure, diabetes, smoking, being overweight or obese, high LDL, and a sedentary lifestyle-already allow doctors to do a good job at identifying the people who should be treated with drugs. “Taken together these risk factors can probably catch the large majority [of people headed for] heart attacks,” said Dr. Atkins in a telephone interview.

After doing a call-in show for National Public Radio, Dr. Mosca worried that people got the wrong impression from news reports. “Consumers might misinterpret this new study to mean that LDL cholesterol is not important because it has been shown statistically that CRP is a little bit better predictor,” she said. “Well, we can say the same thing about hundreds of other risk factors. But LDL reduction has been shown to reduce death and disability, and CRP reduction has not.”

But half of all heart attacks occur in people with normal cholesterol levels-doesn’t that suggest high cholesterol isn’t such an important risk factor? “The reason why so many people with heart disease have so-called normal cholesterol levels is that normal is too high in the U.S.,” answered Dr. Mosca. “If our LDLs were cut in half [to the level] they are in Asia, we wouldn’t have so much heart disease,” she emphasized. “There is virtually no heart disease in countries where the total cholesterol is less than 150.”

The point that cholesterol levels shouldn’t be viewed in isolation was underscored by Dr. Atkins. “People hear that half of all heart attacks occur in people with normal cholesterol levels and think ‘that could be me,’ but the reality is that many of those people have diabetes, they smoke, or have hypertension,” he explained. “Only a very small percentage of heart attacks occur in people who don’t have multiple cardiac risk factors.” Dr. Atkins is concerned that most doctors still focus too narrowly on elevated cholesterol levels, when they should step back and look at the big picture-that is, the full range of major established risk factors for heart disease-and then target the intensity of the therapy accordingly.

Statins are the cholesterol-lowering drugs of choice. Lipitor and Zocor, the two top-selling statins, accounted for $4.5 billion and $2.7 billion in retail sales, respectively, in 2001 and the largest increase in prescription drug sales for that year. Low-dose aspirin therapy is another, far less expensive, standard drug recommended for heart attack prevention. There’s pretty good evidence that both drugs are effective even in people without high cholesterol, explained Dr. Atkins. Aspirin’s anti-inflammatory effect may account-at least, in part-for its success as a heart attack preventive, and statins have an anti-inflammatory effect as well as a cholesterol-lowering effect.

Learning that a person has elevated CRP levels isn’t-in most cases-going to change the treatment plan once a doctor assesses the patient’s other risk factors. “If the person is at low risk, it is unlikely that the CRP results will change our recommendations to the patient, we would still recommend exercise, maintaining weight, avoiding smoking, eating well, etc.,” said Dr. Mosca.

“For the very high-risk individual, that is, the person with heart disease, we already know they should be on statin and aspirin therapy, unless it’s contraindicated,” she continued. “For the middle-risk individual, the decision to test should rest on whether or not the treatment is going to be altered by the results,” she continued. “I’ve certainly screened some patients for CRP when I’m on the border for using certain kinds of therapy–after I have got them as good as I can in terms of lifestyle.”

Dr. Mosca said that after the New England Journal of Medicine published her editorial advising against routinely screening all adults for CRP, she received many congratulatory calls and e-mails from cardiologists around the country. All are concerned that CRP testing will be used routinely before research proves its worth.

“Look at hormone therapy,” said Dr. Mosca, referring to the trial that was stopped last summer because the combination of estrogen and progestin was deleterious to the health of older women. “Hormones became the standard of care for the prevention of heart disease, and when the clinical trial showed that the drugs not only didn’t prevent heart disease but caused heart disease in some women, we still have doctors who refuse to believe the information. We need to wait for the clinical trials before we make general public health recommendations to screen every American.”

(December 2002)

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