Celebrex and Potential Heart Disease and Liver Disease: A Personal Account

Russell Eisenman, Ph.D.

University of Texas-Pan American
Department of Psychology
Edinburg, TX 78539-2999
e-mail: eisenman@utpa.edu

 Citation:
Eisenman. (2008). Celebrex and Potential Heart Disease and Liver Disease: A Personal
 Account   International Journal of Psychosocial Rehabilitation. 13(1), 11-16

Abstract
The author took Celebrex for seven years, only to find out that it could be associated with heart disease, which I now have, and other possible diseases, too.  This article discusses some of my experiences and the possible link between Celebrex and heart disease and other illnesses.  It is apparent that while I was helped in various ways, I did not always receive complete, excellent medical advice.
Keywords: Celebrex, heart disease, liver disease, Vioxx, Cox 2 inhibitors, lumbar spinal stenosis.

Introduction
Several studies or scientific reviews have been performed in the area of COX 2 inhibitors and heart disease, including some preventive qualities of aspirin (1-11). There is some evidence that Celebrex and Vioxx increase the risk of heart disease. (12).

I took Celecoxib (Celebrex) for seven years for the pain of lumbar spinal stenosis. That disease causes back and leg pain.  Celebrex seemed to help a lot, causing me to suffer less pain. But, as a COX-2 inhibitor it may have put me at risk for heart disease. Indeed, six years ago I was diagnosed with 90% clogging in two coronary arteries and 70-80% clogging in two other coronary arteries. I do not know if this is coincidental or if the coronary arteries being clogged was somehow caused by my taking Celebrex.
 
I finally decided to stop taking celecoxib (Celebrex) after all the negative publicity about Vioxx (also a COX-2 inhibitor) ensued. I called the nurse of my cardiologist (I do not get to speak to the cardiologist directly, as most people probably find if they try to communicate with their doctor). I got the answering machine and I asked about the wisdom of continuing vs. discontinuing Celebrex. She never returned my call. I called the nurse (or whoever it was who worked in the doctor's office; it might not have been a nurse) of my regular doctor, and this “nurse” incorrectly informed me that Celebrex was taken off the market and I should stop taking it immediately. I informed her that she was thinking of Vioxx which had just been taken off the market, but she wrongly insisted that she was correct.

SEEKING ADDITIONAL HELP
Unable to find out locally what I should do, I sought advice from my brother, a Yale University Ph.D. in medical sociology, who works for a large HMO (Health Maintenance Organization) in another state. He asked some doctors there and one said I should not take Celebrex for more than a year, due to possible liver damage. I had already taken it for seven years. I quit immediately. For two weeks I felt more pain than I should, but after that my pain went away. I still get back and leg pain, especially if I walk to any great extent or bend over. But, after initially helping a lot, Celebrex was apparently no longer doing much for me in everyday matters, and things seemed to work out well when I stopped taking it.

CONCERNS ABOUT VIOXX AND CELEBREX
An excellent summary of information regarding concerns about Celebrex and related drugs can be found in Bennett et al. (13).  Bennett et al. said
“Recent clinical trial data have raised questions about the degree to which patients and their physicians should consider an increased risk of cardiovascular or cerebrovascular events when selecting medications for pain relief. In September 2004, Merck announced a voluntary worldwide withdrawal of Vioxx (rofecoxib) because of an increased risk of heart attack and stroke. In early December 2004, the US Food and Drug Administration (FDA) announced a "black box" warning for Bextra (valdecoxib), stating that its use in patients undergoing coronary artery bypass grafting is contraindicated. A week later, the National Institutes of Health suspended the use of Celebrex (celecoxib) in the APC (Adenoma Prevention with Celecoxib) clinical trial because of increased cardiovascular events. The drug was not removed from the market, but the FDA advised physicians to consider alternate therapy or to use the smallest effective dose of Celebrex. Three days later, the National Institutes of Health announced that the ADAPT (Alzheimer’s Disease Anti-inflammatory Prevention Trial) showed an increase in the risk of cardiovascular events in patients given naproxen but not in those given celecoxib; the trial was halted. At the end of 2004, the FDA issued a Public Health Advisory summarizing the agency’s recent recommendations concerning the use of the nonsteroidal anti-inflammatory drug products (NSAIDs) Vioxx, Bextra, Celebrex, and naproxen.” (13, p. 1713). 
 
Thus, Celebrex was never removed from the market (contrary to what the “nurse” told me) but the federal government did temporarily suspend its use in a clinical trial, because of concern about possible increased risk of heart attack.
 
Presented below is information from the U.S. Food and Drug Administration regarding Celebrex (14), which raised questions about using the drug.
 
THE U. S. FOOD AND DRUG ADMINISTRATION ALERT ON CELEBREX
Patient Information Sheet
Celecoxib (marketed as Celebrex)
This is a summary of the most important information about Celebrex. For details, talk to your healthcare provider.

What is Celebrex?
Celebrex is used to:
relieve symptoms of osteoarthritis (the arthritis caused by age-related “wear and tear” on bones and joints)
relieve symptoms of rheumatoid arthritis in adults
manage acute pain in adults (like the short term pain you can get after a dental or surgical operation)
treat painful menstrual cycles
reduce the number of colon and rectum growths (colorectal polyps) in patients with a disease called Familial Adenomatous Polyposis (FAP). FAP is an inherited disease in which the rectum and colon are covered with many polyps. Celebrex is used along with the usual care for FAP patients such as surgery and exams of the rectum and colon.
 
Who Should Not Take Celebrex?
Do not take Celebrex if you:
have had an allergic-type reaction to sulfa medicines.
have had asthma, hives or allergic-type reactions after taking aspirin or other NSAID (nonsteroidal anti-inflammatory drugs) medicines. If you have asthma, you may have aspirin-sensitive asthma. If an aspirin-sensitive asthmatic takes aspirin it can cause severe narrowing of the airway (bronchospasm), and even death. Since this type of reaction also has occurred after taking NSAIDs Celebrex should not be given to aspirin-sensitive patients.
Some examples of NSAIDs are ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), diclofenac (Voltaren, Cataflam), and ketoprofen (Orudis). You can ask your doctor or pharmacist for a complete list of these medications.
are pregnant, especially during your last 3 months

What are The Risks?
Celebrex and other NSAID medicines can cause serious problems such as:
Stomach ulcers that bleed. The chance of this serious problem increases the longer you take Celebrex, but it can also happen suddenly. Stop taking Celebrex and call your healthcare professional right away if you get a burning stomach pain, black bowel movements that look like tar, or vomit that looks like blood or coffee grounds.
 
Liver damage. Some of the warning signs of liver damage are nausea, vomiting, tiredness, loss of appetite, itching, yellow coloring of skin or eyes, “flu-like” symptoms and dark urine. If this happens, stop taking Celebrex and call your healthcare professional right away.
 
Kidney problems that include sudden kidney failure or worsening of kidney problems that you already have.
 
Fluid retention (holding of water in your body) and swelling. Fluid retention can be a serious problem if you have high blood pressure or heart failure.
In addition to the serious side effects listed above, some common, but less serious side effects with Celebrex may include:
headache
indigestion
upper respiratory tract infection (a "cold")
diarrhea
sinus inflammation
stomach pain
nausea

What Should I Tell My Healthcare Professional?
Tell your healthcare professional if you:
have heart problems or high blood pressure
have liver or kidney problems
have or had stomach ulcers or stomach bleeding
have asthma
are allergic to aspirin or other NSAID medicines
are trying to become pregnant, are already pregnant, or are breast-feeding

Are There Any Interactions With Drugs or Foods?
Tell your healthcare professional about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how Celebrex works or Celebrex may affect how your other medicines work. Your healthcare professional may have to adjust your dose or watch you closely if you take any of the following medications:
certain blood pressure medicines called ACE inhibitors
furosemide
fluconazole or ketoconazole
phenytoin
warfarin
aspirin
Celebrex FDA Approved 1998
Patient Information Sheet Revised 04/2005
Patient Information Sheet - Questions? Call Drug Information 301-827-4570
Date created: April 7, 2005

Conclusion
In conclusion, there is no way to know for sure if Celebrex led to my coronary artery disease or my current liver problems (see below), but I should have received warnings from doctors about that possibility and I should have been warned about not using Celebrex for more than one year due to possible liver damage.  As a patient, I may have been put at risk unnecessarily, for heart disease and for liver damage.  More information from doctors and nurses would have been appropriate and perhaps very beneficial. 

I have lumbar spinal stenosis, which involves a wearing away of the protective covering of the spinal cord.  Spinal cord problems can be associated with psychological problems, as well, as recently shown by Craig, Tran, Lovas, and Middleton (15). And pain can lead to loss of intimacy, as shown by Bral, Shaughnessy and Eisenman (16).   Initially, Celebrex helped ease some of the pain associated with lumbar spinal stenosis.  But, the threat of heart disease made me give it up, after seven years usage. 

 I also have heart disease (specifically, coronary artery disease) although the blockage is now less than when originally diagnosed.  However, the medical tests done on me in recent years do not allow my cardiologist to say exactly how much less blockage there is.  Probably, quite a bit of blockage remains. Heart disease can also lead to psychological problems, as well as the obvious medical ones. Thus, I have suffered from physical and, likely, psychological problems due to limitations on what I can do, imposed by my conditions.  And, some of my problems may have been caused by medicine intended to help me.  In fact, I just recently had a Hida Scan to evaluate my liver, and it is barely functioning.  My family doctor suggested that I either have my liver taken out or avoid dairy, fatty, and greasy foods.  I am opting for the latter.

I previously wrote of some my experiences with physical disability (17).  This current article takes the discussion of illness further, to consider other diseases and to consider if Celebrex is potentially harmful.  Not all treatment will be ideal, and often patients will receive less help than should be the case (18).

 

1. Levesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults.   Ann Intern Med. 2005;142:481-9.

2. Ouellet M, Riendeau D, Percival MD. A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proc Natl Acad Sci U S A. 2001;98:14583-8.

3. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809-17.

4. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-9.

5. Fiorucci S, Distrutti E, Mencarelli A, Morelli A, Laufor SA, Cirino G, Wallace JL. Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin. Br J Pharmacol. 2003;139:1351-9.

6. Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN . Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A. 2004;101:15178-83.

7. Ouellet M, Riendeau D, Percival MD. A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proc Natl Acad Sci U S A. 2001;98:14583-8.

8. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med., 2001;345:1809-17.

9. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-9.

10. Fiorucci S, Distrutti E, Mencarelli A, Morelli A, Laufor SA, Cirino G, Wallace JL. Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin. Br J Pharmacol. 2003;139:1351-9.

11. Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN . Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A. 2004;101:15178-83.

12.  Dr. Lam.com (2004).  Celebrex and Vioxx increase heart disease risk.  http://www.drlam.com/opinion/celebrex.cfm

13.  Bennett, J. S., Daugherty, A., Herrington, D., Greenland, P., Roberts, H. & Taubert, K. A. The Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): A Science Advisory From the American Heart Association  Circulation. 2005;111:1713-1716.

14. U. S. Food and Drug Administration.  (2005, April 7). FDA Alert. Patient information sheet. Celecoxib (marketed as Celebrex).  Washington, DC: U. S. Food and Drug Administration.

15. Craig A, Tran Y, Lovas J, & Middleton J (2008). Spinal Cord Injury and its Association with Negative Psychological States.   International Journal of Psychosocial Rehabilitation. 12 (2), 115-121.

16.  Bral, E., Shaughnessy, M. F., & Eisenman, R. (2002).  Intimacy in people with chronic pain.  International Journal of Psychosocial Rehabilitation, 6, 51-60. 

17.  Eisenman, R. (2001).  Pain and disability: The personal experiences of a clinical psychologist.  International Journal of Psychosocial Rehabilitation, 6, 33-37. 

18.  Eisenman, R. (2002).  Inadequate treatment of pain: Realities in the everyday world.  Journal of Pain and Symptom Management, 23 (4), 272.