Inexpensive Drug Found Best for Renoprotection from Contrast Agent

By John Gever, Staff Writer, MedPage Today
Published: February 26, 2008

ANN ARBOR, Mich., Feb. 26 -- For patients at a high risk of contrast-induced
kidney failure, an inexpensive and widely available pill is the most
renoprotective agent of all, including hydration, found a meta-analysis
here.

A 25-cent N-acetylcysteine pill appeared to provide the most consistent
protection against nephropathy caused by iodine-based imaging contrast
agents, beating out hydration, theophylline, fenoldopam, iloprost, statins,
dopamine, trimetazidine, bicarbonate, ascorbic acid, furosemide, and
mannitol.

So showed the analysis of 41 randomized trials, reported by Aine M.
Kelly, M.D., and colleagues at the University of Michigan in the Feb. 19
issue of Annals of Internal Medicine. This analysis found that
N-acetylcysteine with IV saline hydration showed the most consistent benefit
in preventing contrast-induced nephropathy, as measured by serum creatinine levels when compared with saline hydration alone.

"This drug, which is quick, convenient, inexpensive, and widely available,
with no major side effects, appears to be the best choice to protect those
whose kidneys are most at risk," said Dr. Kelly. N-acetylcysteine is carried
in most pharmacies and costs about 25 cents for a 500-mg tablet, the
researchers said.

The trials involved a total of 6,379 patients and they all compared various
protective drugs with periprocedural hydration. Most patients in the studies
had chronic renal impairment.

Up to 10% of patients with normal renal function suffer kidney injury after
receiving iodine-containing contrast agents, with even higher rates in
patients with pre-existing kidney dysfunction or other risk factors, Dr.
Kelly and colleagues said. These agents are the third most common cause of
acute renal failure.

Those statistics were derived mainly from an earlier generation of
high-osmolar contrast agents. Saline hydration and the introduction of
iso-osmolar or low-osmolar contrast agents such as iodixanol have reduced
the rate of contrast-induced nephropathy, but not totally abolished it, Dr.
Kelly and colleagues said.

"Thus, protective agents must still be considered for patients with severe
renal impairment who are to receive large volumes of contrast agents," they
wrote.

Most of the studies were in the context of coronary angiography or CT scans
where the contrast agent was delivered intra-arterially.

The meta-analysis identified N-acetylcysteine as showing the best results
across 26 studies. The aggregated relative risk of nephropathy with this
agent was 0.62 (95% CI 0.44 to 0.48).

On the flip side, furosemide turned out to significantly increase risk of
nephropathy (RR 3.27, 95% CI 1.48 to 7.26) on the basis of two studies.

Fenoldopam, mannitol, and a combination including furosemide, dopamine, and mannitol all showed no sign of benefit, with nonsignificant increases in
risk of nephropathy.

What Is the Total Cost of Low Back Pain?

Abillion here, a billion there, and pretty soon you're talking about real money," quipped U.S. Senator Everett Dirksen.

Nowhere is this observation more relevant that in the study of low back pain-and its costs. Everyone acknowledges that low back pain is enormously expensive but there is substantial disagreement about its total costs-and discord about how to estimate them accurately.

Simon Dagenais, DC, PhD, and colleagues recently performed a systematic review of low back pain cost-of-illness studies published from 1997 to 2007. They found 21 relevant investigations. (See Dagenais et al., 2008.) These employed a variety of different methods and arrived at substantially different conclusions. "Estimates of the economic costs in different countries vary greatly depending on study methodology but by any standards they must be considered a substantial burden on society," these researchers observed.

Dagenais and colleagues could not find any studies that accurately estimated the total costs of low back pain in the United States. And they noted that it won't be possible to come up with cost-effective solutions in the management of low back pain without these data. "Cost of illness studies summarizing the economic burden of a particular disease must be considered by all stakeholders, including patients, clinicians, and third-party payers, when deciding on the allocation of scarce healthcare resources," they pointed out.

Those seeking to develop miracle cures for low back pain need to look well beyond the clinic in gauging the impact of new treatments and management strategies. "From studies conducted outside the United States, it appears that direct medical costs represent only a small proportion of the total costs of low back pain..." according to Dagenais et al. Indirect costs from work absence, long-term disability claims, and lost productivity account for the lion's share of back pain's economic burden. And the prevention of long-term disability is likely to be the most important goal in reducing the economic burden of low back pain.

Reference: Dagenais S et al., A systematic review of low back pain costs of illness studies in the United States and internationally, The Spine Journal, 2008; 8:8-20.

Georgia Girl Helps Link Autism to Childhood Vaccines

By ALISON YOUNG
The Atlanta Journal-Constitution
Published on: 03/06/08

In a move autism family advocates call unprecedented,
federal health officials have concluded that childhood
vaccines contributed to symptoms of the disorder in a
9-year-old Georgia girl.

While government officials continue to maintain that
vaccines don't cause autism, advocates say the recent
settlement of the girl's injury case in a secretive
federal vaccine court shows otherwise.

The U.S. Department of Health and Human Services has
concluded the family of Hannah Poling of Athens is
entitled to compensation from a federal vaccine injury
fund, according to the text of a court document in the
case. The amount of the family's award is still being
determined.

The language in the document does not establish a
clear-cut vaccine-autism link. But it does say the
government concluded that vaccines aggravated a rare
underlying metabolic condition that resulted in a
brain disorder "with features of autism spectrum
disorder."

In an interview Wednesday with The Atlanta
Journal-Constitution, Hannah's parents, Jon and Terry
Poling, said the government's concession in the case
will help pay for the numerous therapists and other
medical experts their autistic child needs — now and
for the rest of her life.

"At least we have some commitment from the government
to take care of Hannah when we're gone," said Dr. Jon
Poling, a neurologist.

But the case also thrusts the family into a national
spotlight in the controversial public debate over
whether vaccines have played some role in the growing
number of U.S. children diagnosed with autism. Of
particular concern to some families is the
mercury-based preservative thimerosal, not used in
child vaccines (except for some flu shots) since 2001.

Hannah's case was one of three vaccine-court test
cases alleging that thimerosal caused the children's
autism. The other cases go to trial in May.

Suspicion of vaccines is fueled in part by vocal
advocates — including radio shock jock Don Imus and
actress Jenny McCarthy — speaking out on radio and TV
shows such as "Oprah" and "Larry King Live."

Even Republican presidential candidate Sen. John
McCain said on the campaign trail that "there's strong
evidence" that a preservative in vaccines is fueling
the dramatic rise in autism cases across the country.

As many as 1 in 150 children in some communities have
autism disorders, says the Centers for Disease Control
and Prevention.

"We need to recognize this is a national crisis," Jon
Poling said.

Autism is a lifelong neurological disorder that causes
problems with communication and the ability to have
normal social interactions. Autism and related autism
spectrum disorders cover a range of symptoms that can
vary from mild to severe. The cause is unknown, but
scientists believe genes may play a role.

Pediatricians and public health officials worry that
this case may cause fear among some parents and prompt
them to refuse to vaccinate their children, and put
them in real danger from measles, whooping cough and
other diseases.

The risks of diseases are real risks," said Dr.
Melinda Wharton, deputy director of CDC's National
Center for Immunization and Respiratory Diseases.
Numerous large studies don't support a relationship
between vaccines and autism, according to the CDC and
the Institutes of Medicine.

The Georgia girl's case – and its implications in the
vaccine-autism debate – raise more questions than it
answers, experts say.

Some medical experts say it's difficult to fully
assess the case because the federal vaccine-court
documents are sealed from public view.

"It raised a lot of questions for us," said Dr. David
Tayloe Jr., president-elect of the American Academy of
Pediatrics. The national medical group's leadership
has been seeking more information about Hannah's
vaccine-court case since last week when a sealed
vaccine-court document detailing the government's
settlement was posted on the Internet by an autism
book author, then circulated widely among autism
groups.

The pediatrics association has been trying to get
access to official documents in the case so medical
experts can delve into the science, assess whether
there are implications for other children and answer
questions from doctors and families.

"Our responsibility is to make sure the public is
given good information and make sure the hype doesn't
distract from public health," Tayloe said. "I still
would not think that we're going to have evidence
showing a role of vaccines actually causing autism."

According to the leaked document posted online, the
government's Division of Vaccine Injury Compensation
concluded that five shots Hannah received in July
2000, when she was 19 months old, "significantly
aggravated an underlying mitochondrial disorder" and
resulted in a brain disorder "with features of autism
spectrum disorder."

Sallie Bernard, executive director of the national
autism advocacy group SafeMinds, called the case
"unprecedented" in that a link between vaccines and
autism is being made public. Federal health officials
"have insisted there is no link at all between
vaccines and vaccine components and autism. And
apparently that is not true," she said.

The case also is significant because other autistic
children have mitochondrial disorders, Bernard said.
"The question is: What is the proportion?"

Robert Krakow, a New York attorney representing other
autistic children in vaccine court, said the
significance of the case is "potentially explosive."
He said he has several clients with similar histories.

Hannah requires one-on-one care at all times, said her
mother, Terry Poling, a nurse and lawyer. The Polings
described how Hannah was a normal, verbal toddler
until she received several vaccines during a well-baby
visit. Within 48 hours of the shots, she developed a
high fever and inconsolable crying and refused to
walk. She stopped sleeping through the night. Within
three months after receiving the vaccine, she began
showing signs of autism, including spinning and
staring at lights and fans. For a while, she lost her
ability to speak.

Then, within six months after the shots, as the family
came to grips with the likelihood that she was
autistic, they turned to leading experts in neurology.
"I had to know. My daughter didn't just suddenly
develop autism for no reason," Terry Poling said.

Hannah's father co-authored an article about her case,
which was published in the Journal of Child Neurology
in 2006.

Hannah, who has two older brothers, continues to have
mild to moderate symptoms of autism. The family says
early and ongoing intensive therapy has been critical
for her.

"The biggest question right now for the public is: How
unique is Hannah's case?" said Jon Poling. Poling said
he suspects there are other children like Hannah.

Cliff Shoemaker, the Polings' attorney, said the
family has filed a petition with the vaccine court to
unseal all of Hannah's records and allow both the
family and the government to fully discuss the case.

Despite this, a spokesman for the U.S. Department of
Justice, which reprersents the government in court
cases, would not grant interviews or explain to the
AJC why it isn't releasing the records. HHS officials,
who administer the vaccine compensation fund, also
declined to be interviewed, citing the court's
confidentiality requirements.

Shoemaker said the government's November concession in
the case is public, but the government's reasons
aren't. "I'm not aware of any other conceded autism
cases," he said.

Congress created the National Vaccine Injury
Compensation Program in 1988 after widespread lawsuits
against manufacturers and health-care providers
stemming from reports of side-effects of a version of
the diphtheria-tetanus-pertussis vaccine used in the
1980s.

With companies getting out of the vaccine business for
liability reasons, Congress established the program
and a trust fund to serve as a no-fault alternative
for resolving certain vaccine injury claims.

The average injury compensation to an individual in
vaccine court has been about $1 million. In fiscal
year 2007, more than $91 million was awarded to people
harmed by vaccines.

A Rip-Off by Health Insurers?

IF THIS KIND OF CHEATING IS HAPPENING IN THE USA, CAN HERE BE ANY BETTER?

Have health insurers been systematically cheating patients and doctors of fair reimbursement for medical services? That is the disturbing possibility raised by an investigation of the industry's arcane procedures for calculating "reasonable and customary" rates.

The investigation, by the New York State attorney general, Andrew Cuomo, and his staff, suggests that these procedures - used by major insurance companies to determine what they will pay when patients visit a doctor who is not in the company's network - may be rigged to shortchange the beneficiaries.

When patients visit an out-of-network doctor, insurers typically agree to pay 80 percent of the reasonable and customary rate charged by doctors in the same geographic area. The patient is stuck with the rest, and as any patient knows, that rate always seems to fall short of what their own doctor is charging. If the attorney general's investigators are right, we can understand why.

The numbers are mainly compiled by an obscure company known as Ingenix, which - as it turns out - is owned by UnitedHealth Group, one of the nation's largest health insurers. Ingenix collects billing information from UnitedHealth and other health care payers to compile a database that is then used by the insurers to determine out-of-network reimbursement rates.

This system is an invitation for abuse. UnitedHealth owns the company whose database will affect its costs and profitability, so both have a strong financial interest in keeping reimbursement rates low. Even Ingenix seems unwilling to stand behind its numbers. In licensing its database to insurers, it stresses that the data is "for informational purposes only" and does not imply anything about "reasonable and customary" charges. Yet that is precisely what the health insurers use the data for, as Ingenix knows, according to investigators.

Mr. Cuomo and the American Medical Association, which has a long-standing suit filed against Ingenix and various UnitedHealth companies, claim that the data is manipulated. They claim that health insurers and Ingenix disproportionately eliminate high charges, thus skewing the numbers for customary charges downward.

Mr. Cuomo also says that Ingenix pools the charges for services performed by low-paid nurses and physician assistants with those performed by high-paid doctors. And he says the company fails to account for the patient's condition and type of facility where the service was provided - factors that can drive up costs. He also contends that Ingenix uses outdated information, which would guarantee that reimbursement rates will always lag behind medical inflation.

The A.M.A.'s more detailed legal complaint also charges that the database dilutes prices in high-cost locations by combining them with low-cost areas, and includes prices that reflect in-network discounts.

The attorney general's investigators did their own survey and concluded that $200 is the fair market rate in New York City and Nassau County for a 15-minute consultation with a doctor for an illness of low to moderate severity. Ingenix, the investigators said, calculated the rate as $77, of which United would pay $62, leaving the patient to pay $138. UnitedHealth disputes those numbers, so the attorney general will need to offer a fuller explanation of how they were derived.

Mr. Cuomo has announced his intention to sue UnitedHealth, Ingenix and three other subsidiaries, and has subpoenaed data from 16 other health insurers. Whatever that investigation unearths, it is already clear that the system for calculating "reasonable and customary" charges ought to be reformed by making it truly independent and objective. No consumer can reasonably trust numbers generated by a company whose loyalties and financial interests lie with the health insurers.

Jessica Vega After Gardasil

" The FDA adverse event reports on the HPV vaccine read like a catalog of horrors," stated Judicial Watch President Tom Fitton. "Any state or local government now beset by Merck's lobbying campaigns to mandate this HPV vaccine for young girls ought to take a look at these adverse health reports. It looks as if an unproven vaccine with dangerous side effects is being pushed as a miracle drug." Judicial Watch filed its request on May 9, 2007, and received the adverse event reports from the FDA on May 15, 2007. Judicial Watch has posted the adverse event reports on their Internet site at: http://www.JudicialWatch.org." - Judicial Watch, May 23 statement"


Student Natasha D'Souza said she collapsed and was left paralysed for six hours after being injected. "I couldn't move at all. There were girls dropping like flies, basically," she said. Ms D'Souza said she had been vaccinated in the past but her reaction to Gardasil was different. Fellow student Brooke Levy, who was taken to hospital, said she thought she might pass out or vomit after she was vaccinated. But authorities believed their reactions were likely to be related to having an injection not the vaccine itself." - Danialle Cronin, Canberra Times, Australia


"Her legs are paralyzed, her arms are affected. She is very weak in her arms," said Tondra Vees a family friend. "She has to use a walker. Even with that, she can't get to the bathroom. She can't stand up at all." Vees said the girl has been determined by her doctor to have Guillain-Barre syndrome, an acute, autoimmune condition that can lead to paralysis. The girl.....received her first booster shot of the cervical cancer prevention vaccine Gardasil on May 2....Vees cites a report on the National Vaccine Information Center Web site, nvic.org, in which NVIC president Barbara Loe Fisher states, "There are twice as many children collapsing and four times as many children experiencing tingling, numbness and loss of sensation after getting a Gardasil vaccination compared to those getting a TDAP (tetanus-diphtheria- acellular pertussis) vaccination. There have been reports of facial paralysis and Guillain-Barre syndrome..." - Jo Rafferty, May 17 Nevada Appeal


"Assembly Bill 16 would require pupils to receive shots recommended by the federal government's Advisory Committee on Immunization Practices -- a list that happens to include Gardasil -- after approval by the state health officer. Rick Rollens, a longtime Capitol staffer and lobbyist, pleaded with the Assembly Education Committee to hold up AB 16, saying his son "suffers from vaccine-induced regressive autism" and citing increasing evidence that childhood vaccines play a role in autism. He characterized AB 16 as "an outrageous and arrogant attempt" to shift vaccination mandates from the Legislature to a "non-accountable bureaucrat" and a remote federal committee. Nevertheless, the bill sailed through the Assembly's education and health committees...." - Dan Walters, May 17 Sacramento Bee


"In an editorial published in today's New England Journal of Medicine, the UCSF doctors suggest that there are still too many questions about both the efficacy and the long-term safety of the vaccine, called Gardasil, to warrant making it mandatory for all girls -- as has been suggested in several states, including California. "At this stage, vaccination can still be considered experimental," said Dr. Karen McCune, an associate professor of obstetrics and gynecology at UCSF, who co-authored the editorial. "To be discussing mandatory vaccination when the main clinical trials are still ongoing seems extremely premature. We're feeling like the enthusiasm is driving policy rather than data." - Erin Allday, May 10 San Francisco Chronicle

Barbara Loe Fisher Commentary:
In June 2006, NVIC issued its first press release providing evidence that Merck's GARDASIL vaccine had not been thoroughly tested for safety and efficacy in young girls. In February, NVIC released two detailed reports analyzing vaccine reaction reports filed with the federal Vaccine Adverse Events Reporting System (VAERS), which documented that many girls were suffering atypical collapse with seizure activity and subsequent brain dysfunction, including three cases of facial paralysis and five cases of Guillain Barre syndrome (http://www.nvic.org/Diseases/HPV/HPVHOME.htm).

NVIC has led the opposition to HPV vaccine mandates based on product safety concerns that there is inadequate scientific proof the vaccine is safe and effective for 11 year old girls, who are being targeted by the CDC and Merck for mass use.And it just keeps getting worse and worse. Now three deaths have been reported, along with more reports of paralysis in girls who have gotten the poorly tested HPV vaccine. As usual, the vaccine maker and public health officials are in denial mode, using the unscientific "coincidence" argument in an attempt to cover- up HPV vaccine-related death and neuroimmune dysfunction.

And, still, politicians in California, New York and other states press forward to get GARDASIL mandated even as politicians in many other states are wisely backing off from adding it to state vaccine mandates for school entry.

For those who have watched industry and government cover-up harm caused by DPT, DTaP, MMR, HIB, hepatitis B, chicken pox, pneumococcal, influenza, anthrax and other vaccines during the past quarter century, the HPV vaccine risk cover-up is just another deja vu experience. Same story, different vaccine.

When will it end? When will industry and government health officials, along with pediatricians and nurses injecting children with reactive vaccines, like GARDASIL, stop deluding themselves into believing the public is going to blindly trust and buy the "coincidence" argument forever?

For more information about GARDASIL and HPV infection, go to www.nvic.org. If you or a loved one has experienced a reaction to GARDASIL vaccine or any other vaccine, you can post your story (and a photo) on the International Memorial for Vaccine Victims at http://rs6.net/tn.jsp?t=q5ptjacab.0.od5855bab.oblmlwbab.12517&ts=S0251&p=http%3A%2F%2Fvaccinememorial.org%2F.


Jeffrey Dach MD said...
Gardasil Vaccine: So far 3 deaths and 1,637 Adverse Reaction Reports to FDA

Opponents to Gardasil say things like:

"This vaccine should not be mandated for 11-year-old girls.... It's not been tested in little girls for efficacy. At 11, these girls don't get cervical cancer—they won't know for 25 years if they will get cervical cancer. Giving it to 11-year-olds is a great big public health experiment." Dr. Diane Harper, lead researcher, HPV vaccine development

Objections Listed:

1. The vaccine is costly. ($360 for series of three shots)

2. Lack of testing in 9–13 yr olds.

3. Lack of evidence of duration of protection (estimated duration of 5 years).

4. Efficacy has not been demonstrated and is unknown. In fact, there's already been talk of the need for booster shots.

5. Benefit of Gardasil to 9–13 year olds is dubious. Cervical Cancer affects 45-55 year olds, 40 years later.

6. Questionable Safety when used in conjunction with other vaccines (Hep B and Meningitis ).

7. High rate of vaccine injury: the US Vaccine Adverse Event Reporting System is showing considerable serious injury from this vaccine, especially neurological and immune dysfunction. Included are reports of collapse, paralysis, Guillain-Barre syndrome, dizziness, vomiting, rash, syncope, seizures and headache.

8. Gardasil may actually cause an increase in cervical cancer due to a false feeling of security in the females who receive it and decline PAP smears.

9. Gardasil does not guarantee safety from HPV: Regular Pap screening tests with their incumbent costs will still be needed.

10. The incidence of cervical cancer is low, and it would cost $360 million to pay for vaccine to prevent only 1–2 deaths.

11. HPV is usually benign: The virus clears up on its own within 8–12 months.

12. Pap screening already works and has been very effective in reducing cervical cancer rates.

Mom Says HPV Vaccine Caused Paralysis in 12-Year-Old

Jackelyn Barnard
First Coast News
Feb. 21, 2008 10:10 AM

Brittany is a twelve-year-old who doesn't like to sit still.

The Florida girl played softball. She ran cross country. The plan was to stay on the team and get a college scholarship, but those dreams drastically changed.

"She was walking through my house and collapsed. She told me she couldn't feel her leg. We went right to the hospital," says Christina Bell, Brittany's mom.

Bell says there were no answers at first, but then she started to put the pieces of the puzzle together. Two weeks before her daughter's collapse, Brittany received her first injection of a vaccine called Gardasil.

"The doctor recommended we get the Gardasil shot and I'd been thinking about it because I've seen it on TV all the time," says Bell.

The vaccine, produced by Merck, is to help prevent contracting the Human Papillomavirus or HPV. The virus causes 70 percent of cervical cancer.

Over the last year, the vaccine has been the center of moral controversy, but little has been mentioned about the number of vaccine reactions reported to the FDA. Recent news reports link an association with paralysis and death with the vaccine.

"The reason I'm skeptical with this is this isn't a virus," says Dr. Guy Benrubi, an OB/GYN with Shands.

Dr. Benrubi says the HPV vaccine is one of the safest and he recommended it to his own child.

"The immediate risks are minimal. The FDA looked at those. We have not seen any major catastrophes," says Dr. Benrubi.

Benrubi says the majority of complaints are patients fainting during or after the shot. So far, more than four million vaccinations have been done and nearly 4,000 adverse reactions have been reported.

"Even the worst case scenario, if you have four thousand in four million that is a one to one thousand potential adverse effect," says Dr. Benrubi.

The list of complaints range from temporary blindness, blurry vision, convulsions, seizures and numbness in arms and legs that won't go away.

"If you know something is happening why do you let it continue?" asks Bob Giuliano, Brittany's grandfather.

Giuliano and his daughter want answers as to how they didn't know paralysis could be a possibility for Brittany.

"I am very angry," says Brittany's mom. After months of physical therapy, Brittany still has no feeling in her left leg.

Getting around is difficult. It's hard for Brittany to walk and balance and she often needs a little help.

"She's mad. I can tell she's mad," says Brittany's mom. A little shy, Brittany did not want to talk to us, but she did want her story told so parents and young girls know how her life has changed.

Now she is learning to cope with braces, crutches and a walker. "It's changed everything for us," says Bell.

Brittany's doctors have diagnosed her with Acute Demyelinating Encephalomyelitis or ADEM. It is an inflammation of the brain that has been associated with a vaccination.

"I think there is a little cart before the horse going on here. I'm not saying this is not a good vaccine, but anyone who is going to have their daughter or child have this shot, they need to be fully informed of risks or potential risks associated with it," says Sean Cronin, Brittany's attorney.

Cronin says he can't go after Merck with a lawsuit because Gardasil is now part of a federal fund which pays out to those injured from vaccines.

First Coast News has learned, Gardasil was added to the National Vaccine Injury Compensation Fund just months after it hit the market. "The Federal government would not put it on the list without medical scientific justification," says Cronin.

Brittany's family is filing an injury claim with the government. They are also on a mission to spread the news of what they say can happen with the vaccine.

The family also holds out hope that one day, old Brittany will be back walking and running like she did once before.

"I do wish the doctor would have known and would have said there is a chance that this could happen. If he would have said, I would have never done it," says Bell.

The FDA told First Coast News the adverse reaction reports are not a good indicator of a direct cause or relation with an incident. The FDA also says they have investigated several deaths but did not find any association with the vaccine.

Merck told First Coast News it is unaware of Brittany's case. Merck also says it actively monitors the adverse reaction reports and other databases throughout the world.

As for the vaccine being added to the government vaccine fund, Merck says it is their understanding that all new vaccines are added to the fund.

The Pharmaceutical giant says the latest numbers show that ten million HPV vaccines have been given in the United States.

ROUEN, France, Feb. 28 -- Statin-related adverse effects are rare, and rarer still are tendinous complications, according to a large French post-marketing surveillance program.


Tendinous complications accounted for about 2% of all statin adverse events reported to the French pharmacovigilance network from 1990 to 2005. For the individual years reviewed, the proportion of statin-related adverse effects that involved tendons ranged from 0% to 3.6%.


"Our series suggests that statin-attributed tendinous complications are rare, considering the huge number of statin prescriptions," the authors concluded. "We suggest that prescribers should be aware of tendinous complications related to statins, particularly in risk situations, including physical exertion and association with medications known to increase the toxicity of statins."


Statin-associated tendon impairment had not been reported in previous pre- and postmarketing studies, although sporadic anecdotal reports suggested a possible link. To explore the issue more closely, Dr. Marie and associates retrospectively reviewed data from 31 French pharmacovigilance centers.


For the 16-year period reviewed, 4,597 statin-related adverse events were reported to the pharmacovigilance network. Of those, 96 events (2.01%) involved tendon impairment, consisting of 63 reports of tendinitis and 33 reports of tendon rupture. The Achilles tendon was the affected area in 50 (52.1%) of the cases, and 26 patients (27%) had bilateral tendon manifestations.


The median time to onset of tendon symptoms was 243 days, but occurred as early as 24 hours after starting therapy and as late as 15 years. Tendon symptoms occurred within the first year in 59% of patients.


Statin-attributed tendon complications were considered serious in 36 cases, and 17 patients required hospitalization. Moreover, 19 of the 33 patients who had tendon rupture had significant functional sequelae that included difficulty walking, decreased range of motion, and pain. Of seven patients who stopped and then reinitiated statin therapy, all seven had a recurrence of tendon symptoms.


Tendon complications were reported in patients treated with atorvastatin (Lipitor), simvastatin, pravastatin, fluvastatin (Lescol), and rosuvastatin (Crestor). The authors reported that the complications occurred at recommended dose ranges for all of the drugs.


Predisposing factors beyond statin therapy that might have led to tendon complications were not explored.


Though generally considered safe and associated with minor side effects, statins occasionally cause serious complications, especially musculoskeletal effects that include myositis, rare cases of rhabdomyolysis, and inflammatory myopathies. In clinical trials of statins, myositis occurred in 0.09% to 0.63% of patients and rhabdomyolysis in 1 case per 100,000 patient-years, the authors noted.


Despite their findings, the authors left the door open to the possibility that statins have a closer association with tendon problems than currently recognized. They noted that a literature review uncovered 43 cases of statin-related tendon complications.


"Tendinous manifestations may be an as-yet unreported side effect of statin therapy," they said. "In essence, no cases were reported during the large therapeutic trials, including more than 30,000 patients. However, the fact that statin-related tendon complications have not been described in these large clinical trials may be explained in part by control of factors predisposing to tendinopathy and regular follow-up of trial patients."


They concluded that this literature review suggests that tendon manifestations may be included within the spectrum of adverse effects of statins but future case-control studies are required to confirm this relationship.


"Our study suggests that regular tendinous clinical examination may be required in statin-treated patients, particularly during the first year following statin therapy initiation," they added.


The authors had no disclosures.

Source reference:
Marie I, et al "Tendinous disorders attributed to statins: A study on ninety-six spontaneous reports in the period 1990-2005 and review of the literature" Arthritis Rheum 2008; 59: 367-372.