1000s die from NSAIDS...

[Guest guest]

http://www.healthsentinel.com/NSAIDs/NSAIDs.htm

 

Advertising may be described as the science of arresting the human intelligence

long enough to get money from it. - Stephen Leacock

 

 

 

 

Nonsteroidal anti-inflammatory drugs, often referred to as NSAIDS, are assumed

to be well tolerated and are widely used as an initial therapy for common

inflammation. Everyone is familiar with these types of drugs with millions

using them for pain relief. They range from over the counter aspirin and

ibuprofen to a whole host of prescription brands. These pharmaceutical agents

constitute one of the most widely used class of drugs, with more than 70 million

prescriptions and more than 30 billion over-the counter tablets sold annually in

the United States alone. NSAIDs are often called nonsteroidal because they are

not steroids. Steroids affect inflammation by suppressing part of the immune

system, which is the body’s natural healing response to trauma. Instead NSAID

drugs mainly inhibit the body's ability to synthesize prostaglandins.

Prostaglandins are a family of hormone-like chemicals, some of which are made in

response to cell injury.

 

Common over the counter names include: ibuprofen (Advil®), naproxen (Aleve®),

and aspirin (Bayer®). Perscription brands include: celecoxib (Celebrex®),

diclofenac (Voltaren®), etodolac (Lodine®), fenoprefen (Nalfon®), indomethacin

(Indocin®), ketoprofen (Orudis®, Oruvail®), ketoralac (Toradol®), oxaprozin

(Daypro®), nabumetone (Relafen®), sulindac (Clinoril®), tolmetin (Tolectin®),

and rofecoxib (Vioxx®).

 

It is generally stated that the side effects of NSAIDs are fairly mild causing a

possible upset stomach and/or nausea and vomiting. It is often recommended that

the stomach upset, nausea and vomiting can be avoided by taking the medication

with a little food or milk. It is also well stated that long-term or extensive

ingestion of NSAIDs can result in the drugs having toxicity to the kidneys and

also to the lining of the stomach, possibly causing ulcers. Except for these

mild warning these medications are considered safe and effective. But in

reality just how safe are these types of drugs?

 

A statement from a July 1998 issue of The American Journal of Medicine states

the following:

 

“Conservative calculations estimate that approximately 107,000 patients are

hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related

gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths

occur each year among arthritis patients alone. The figures of all NSAID users

would be overwhelming, yet the scope of this problem is generally

under-appreciated.” [1]

 

 

And again a year later (June 1999) in the prestigious New England Journal of

Medicine there is a similar statement:

 

“It has been estimated conservatively that 16,500 NSAID-related deaths occur

among patients with rheumatoid arthritis or osteoarthritis every year in the

United States. This figure is similar to the number of deaths from the acquired

immunodeficiency syndrome and considerably greater than the number of deaths

from multiple myeloma, asthma, cervical cancer, or Hodgkin’s disease. If deaths

from gastrointestinal toxic effects from NSAIDs were tabulated separately in the

National Vital Statistics reports, these effects would constitute the 15th most

common cause of death in the United States. Yet these toxic effects remain

mainly a “silent epidemic,” with many physicians and most patients unaware of

the magnitude of the problem. Furthermore the mortality statistics do not

include deaths ascribed to the use of over-the-counter NSAIDS.” [2]

 

What these journal articles are stating is shocking. Over 100,000 people are

hospitalized for GI bleeding and of those 16,500 die every year. And these

values are considered “conservative”. Also the figures only include

prescription NSAIDs used to treat only arthritis and only in the United States.

If prescription and over the counter NSAID-related hospitalizations and death

rates were counted for not only arthritis, but for all conditions, and

throughout the world, the figures would no doubt be enormous. Taking those

figures and applying them over the many years that this class of drug that has

been available since the early 1970s and the numbers would be horrific. And

yet, no study to date has attempted to quantify these figures. A graph from the

same article shows this alarming statistic relative to other causes of deaths.

 

 

 

Figure 1. U.S. Mortality Data for Seven Selected Disorders in 1997. A total of

16,500 patients with rheumatoid arthritis or osteoarthritis died from the

gastrointestinal toxic effects of NSAIDs. Data are from the National Center for

Health Statistics and the Arthritis, Rheumatism, and Aging Medical Information

System. [3]

 

Looking at this information from another perspective we can compare yearly

estimated NSAID deaths since 1991 with the number of murders committed with

firearms each year in the United States and with the number of U.S. Forces

killed in Vietnam if that war was being fought in the 1990s instead of

1961-1972. Although no data shows the exact number of NSAID deaths each year

7,600 deaths were estimated in 1991 and 16,500 deaths were estimated in 1998.

The graph presented here assumes a linear increase in the number of deaths,

however the actually numbers are unknown. Once again the 16,500 NSAID deaths

per year is considered conservative and does not include over the counter

medications or prescriptions for other conditions other than arthritis.

 

 

Figure 2. Comparison of NSAID related deaths with yearly murders with firearms

and number of US forces killed in Vietnam. [4]

 

 

Another important observation is that most people have no warning signs that

these drugs are causing them internal damage before they ending up in the

hospital with a serious medical condition. And as we have seen from the

statistics, approximately 10% of these hospitalizations end in death.

 

“… 81% of the patients who were hospitalized with a serious GI complication did

not have any prior GI adverse event. This finding has important clinical and

health policy implications. Since most patients who have a hospitalization do

not have a prior GI side effect and most patients who have a side effect are not

subsequently hospitalized, a clinician cannot depend on early GI symptoms to

identify patients at risk or provide a warning for subsequent serious

complications.” [5]

 

Since there is knowledge that these medications can cause stomach upset, other

drugs, such as antacids, are prescribed to alleviate those symptoms. And while

these additional medications may provide symptom relief they do not prevent the

underlying damage that is occurring. And by hiding these symptoms antacids

actually increase the chances of having a serious problem. Despite this

evidence, many patients are prescribed these additional drugs.

 

“The use of antacids and H2 receptor antagonists for prophylaxis against serious

NSAID-induced GI complications remains controversial. Previous research has

shown that although these agents suppress symptoms, they do not prevent

endoscopically documented NSAID-induced gastric ulcers, the most common

pathology seen with NSAIDs. There is no data on the role of antacids and H2

receptor antagonists in actually preventing clinically significant serious GI

complications. Nevertheless, antacids and H2 receptor antagonists are widely

used in combination with NSAID therapy (30% patients in our study). Our data

indicate that patients taking antacids and H2 receptor antagonists are not

afforded a lower risk of significant GI events. Indeed, asymptomatic patients

who started to take antacids or H2 receptor antagonists prophylactically had a

higher risk for serious GI complication compared with those who did not take

these medications.” [6]

 

Even aspirin, the first NSAID that was synthesized over 100 years ago by Felix

Hoffman at Bayer industries is not free of risk. And considering that aspirin

is being highly recommended to reduce the incidence of heart disease we must

consider the gastrointestinal damage being caused as well.

 

“We found that no particular dose of aspirin between 75 mg and 300 mg daily

currently used in cardiovascular prophylaxis is free of risk of causing bleeding

from gastric or duodenal ulcers. Even very low (75 mg) doses of aspirin

reportedly caused gastric bleeding in volunteers. … Some 10,000 episodes of

ulcer bleeding occur in people aged 60 and over each year in England and Wales.

Other data of ours suggest that some 3,500 of these will be takers of

non-aspirin non-steroidal anti-inflammatory drugs, and if our current figures

are representative 1,700 or 17% of the total will be taking prophylactic aspirin

compared with 8% of community controls. If may be deduced that 900 of the

10,000 episodes could be associated with and ascribed to prophylactic aspirin

use. A general change to low doses (75 mg) of aspirin would not eliminate the

risk, but again if our figures are soundly based, would reduce the risk by about

40% compared with 300 mg doses and by 30% compared with 150 mg doses.” [7]

 

Unfortunately the risk of hospitalization and death is not the only possibility

from taking these types of drugs. Other studies also indicate that the risk of

Congestive Heart Failure (CHF) while using NSAIDs is also quite substantial.

One author suggested that the number of deaths could be similar to those that

are being seen with gastrointestinal bleeding. If so the numbers of deaths

attributed to NSAIDs would increase dramatically from the already large figure

of 16,500.

 

“In this study we found that recent use of NSAIDs by elderly patients doubles

the odds of being admitted to hospital with an episode of CHF [Congestive Heart

Failure]. The estimated relative risk for first admission with heart failure,

and the risk of this outcome was increased substantially by NSAID use in those

with a history of heart disease. … Assuming the association between use of

NSAIDs and CHF is unconfounded, the disease burden attributable to these drugs

may be large – approaching the levels of morbidity and mortality that we have

previously documented for serious upper gastrointestinal complications of NSAID

use in NSW [New South Wales].” [8]

 

The risk appears to be especially great in patients using diuretics.

 

“During periods of concomitant use of diuretics and NSAIDs, a 2-fold increased

risk of hospitalization for CHF [Congestive Heart Failure] was found compared

with periods of diuretic used only. Patients with a history of heavy diuretic

use showed an increased risk. This may lead to the hypothesis that an existing

condition of CHF that is being treated with diuretics is challenged by the

introduction of NSAIDs.” [9]

 

Since these medications are marketed and used worldwide we should expect there

to be NSAID hospitalizations and deaths worldwide. Although the available

information is limited, there is evidence of this occurring in Germany and Great

Britain.

 

“We thus calculated the total number of NSAID-associated hospital admissions for

gastrointestinal PUB [Perforations, Ulcers and Bleeding] in the GKV [German

statutory health-insurance fund] to be 10,700 per year, necessitating 157,000

hospital days and total costs of DM 125 million. 1,100 to 2,200 fatal cases in

the GKV annually were thus expected. Multiplying these figures by a factor of

1.1 provides estimates for the entire German populations.” [10]

 

 

 

“… studies from Great Britain which show an estimated 12,000 NSAID-related

hospital admissions and 4,000 NSAID-related deaths.” [11]

 

Not only are there enormous deaths and suffering associated with NSAIDs there is

also a tremendous financial cost.

 

“… the annual number of hospitalizations in the United States for serious

gastrointestinal complications is estimated to be at least 103,000. At an

estimated cost of $15,000 to $20,000 per hospitalization, the annual direct

costs of such complications exceeds $2 billion.” [12]

 

Is this information of NSAID recent? Unfortunately the answer is no. Various

medical journals in 1991 showed there was information on the toxicity of these

types of drugs.

 

“These results led the investigators to suggest that in the United States the

syndrome of NSAID-associated gastropathy accounts for at least 2600 deaths and

20,000 hospitalizations each year in patients with rheumatoid arthritis alone.”

[13]

 

 

 

“Overall death estimates are similarly disquieting. Conservative calculations,

counting only excess deaths, indicate that about 7,600 deaths/year in the United

States are attributable to NSAID use. The Food and Drug Administration suggests

even higher figures, estimating NSAID use accounts for 10,000 to 20,000

deaths/year. These figures are comparable to Hodgkin’s disease or acquired

immunodeficiency syndrome and represent a serious problem.” [14]

 

 

In spite of this knowledge, the FDA did little. Over time certain NSAID

medications that were especially toxic were withdrawn or banned, research slowly

progressed to find less toxic NSAIDs or to find other medications that would

counteract the damage being created. But there was no large-scale public alert

to the potential hazards of these drugs. Instead the FDA opted to simply

provide a warning label on NSAIDs.

 

 

 

“Gastrointestinal adverse reactions with long-term use of NSAIDs. A general

paragraph regarding the risk of gastrointestinal ulcers, bleeding, and

perforation with long-term NSAID treatment is being developed for inclusion on

the labels of all NSAIDs. By life table analysis of prospectively collected

data from multiple NSAID submissions, the FDA estimates that these serious

events occur in approximately 1-2% of patients using NSAIDs for 3 months, and in

approximately 2-5% using them for 1 year. The cumulative risk appears to

increase with the duration of therapy and to be greater in patients with

previous peptic ulcer disease. Fatal outcomes are more likely in elderly or

debilitated patients. Higher dosages of NSAID probably entail greater risk that

lower dosages.” [15]

 

NSAIDs are truly a silent epidemic that have caused a tremendous amount of pain

and death. Public knowledge of this tragedy is virtually non-existent with an

enormous amount of information written primarily existing within the sanctuary

of medical libraries. Pharmaceutical companies still market and promote

worldwide sales of these toxic substances and governmental agencies have done

nothing of any substance to alert the public. Pharmaceutical companies are now

creating a new class of NSAIDs called COX-2 inhibitors that “maybe” less toxic

than their earlier creations. But these efforts come at the same time large

numbers of needless hospitalizations and deaths are occurring. And considering

that these companies originally created such toxic substances can we trust them

to create newer drugs to replace their failures? Also, like the original drugs

large scale long term studies are not performed before vigorous market campaigns

and sales have promoted these new “safer” drugs. Instead, once again, the

people will play guinea pig and years later we will learn the results of their

latest experiments.

 

 

 

 

[1] Singh Gurkirpal, MD, “Recent Considerations in Nonsteroidal

Anti-Inflammatory Drug Gastropathy”, The American Journal of Medicine, July 27,

1998, p. 31S

 

[2] Wolfe M. MD, Lichtenstein D. MD, and Singh Gurkirpal, MD, “Gastrointestinal

Toxicity of Nonsteroidal Anti-inflammatory Drugs”, The New England Journal of

Medicine, June 17, 1999, Vol. 340, No. 24, pp. 1888-1889.

 

[3] Wolfe M. MD, et al, The New England Journal of Medicine, June 17, 1999, Vol.

340, No. 24, pp. 1888-1889.

 

[4] Fries James F., “NSAID Gastropathy: The Second Most Deadly Rheumatic

Disease? Epidemiology and Risk Appraisal”, Journal of Rheumatology, 1991,

(Supplement 28), Vol. 18, pp. 6-10; Singh Gurkirpal, MD, The American Journal of

Medicine, July 27, 1998, p. 31S

 

[5] Singh Gurkirpal, MD, Ramey Dena, Morfeld Dianne, Shi Hong, MS, Hatoum Hind,

PhD, and Fries James, MD, “Gastrointestinal Tract Complications of Nonsteroidal

Anti-inflamatory Drug Treatment in Rheumatoid Arthritis”, Archives of Internal

Medicine, July 22, 1996, Vol. 156, pp. 1530-1536

 

[6] Singh Gurkirpal, MD, et al, Archives of Internal Medicine, July 22, 1996,

Vol. 156, pp. 1530-1536

 

[7] Weil, J., Colin-Jones D., Langman M., Lawson D., Logan R., Murphy M.,

Rawlins M., Vessey M., and Wainwright P., “Prophylactic aspirin and risk of

peptic ulcer bleeding”, British Medical Journal (BMJ), April 1, 1995, Vol. 310,

pp. 827-829

 

[8] Page J. MBBS(Hons) and Henry D. MBchB, “Consumption of NSAIDs and the

Development of Congestive Heart Failure in Elderly Patients”, Archives of

Internal Medicine, March 27, 2000, Vol. 160, pp. 777-784

 

[9] Heerdink E., PhD, Leufkens H., PhD, Herings R., PhD, Ottervanger J., MD,

Stricker B., MD and Bakker A., MD, “NSAIDs Associated With Increased Risk of

Congestive Heart Failure in Elderly Patients Taking Diuretics.”, Achrives of

Internal Medicine, May 25, 1998, Vol. 158, pp.1108-1112

 

[10] Bolten W., Lang B., Wagner A., and Krobot K., “Consequences and Costs of

NSAID-Induced Gastropathy in Germany”, Akt Rheumotol, 1999, Vol. 24, pp. 127-134

 

[11] Bolten W., et al, Akt Rheumotol, 1999, Vol. 24, pp. 127-134

 

[12] Wolfe M. MD, et al, The New England Journal of Medicine, June 17, 1999,

Vol. 340, No. 24, pp. 1888-1889.

 

[13] Brooks Peter, MD and Day Richard, MD, “Nonsteroidal Anti-Inflammatory Drugs

– Differences and Similarities”, The New England Journal of Medicine, June 13,

1991, Vol. 324, No. 24, pp. 1716-1725

 

[14] Fries James F., “NSAID Gastropathy: The Second Most Deadly Rheumatic

Disease? Epidemiology and Risk Appraisal”, Journal of Rheumatology, 1991,

(Supplement 28), Vol. 18, pp. 6-10

 

[15] Paulus Harold, “FDA Arthritis Advisory Committee Meeting: Risks of

Agranulocytosis/Aplastic Anemia, Flank Pain, and Adverse Gastrointestinal

Effects with the Use of Nonsteroidal Anti-Inflammatory Drugs”, Arthritis and

Rheumatism, May 1987, Vol. 30, No. 5, pp. 593-595

 

Roman Bystrianyk is an investigative reporter for HealthSentinel.com

 

Last update on October 30, 2002

 

 

 

Gettingwell- / Vitamins, Herbs, Aminos, etc.

 

To , e-mail to: Gettingwell-

Or, go to our group site: Gettingwell

 

 

 

 

Mail Plus - Powerful. Affordable. Sign up now