Ask an Expert: Arthritis pain relievers

I used to take Bextra for my arthritis, but when the Food and Drug Administration asked Pfizer to stop selling it, my doctor put me on Celebrex. These drugs have been important in helping me move with less pain and stiffness, but I am worried about reports saying that they increase the risk of heart attack or stroke. What should I do?

Answer from Elizabeth Tindall, M.D., rheumatology and immunology physician at Providence St. Vincent Medical Center, and president of the American College of Rheumatology:

You are facing a difficult situation: Scientific information about these and other nonsteroidal anti-inflammatory drugs, or NSAIDs is increasing, but this new information also is raising many questions. It will take more studies, involving many patients over several years, to better understand all of the safety issues. Meanwhile, your arthritis symptoms need to be addressed so you can live a comfortable, productive life.

Let me first address your concerns about the cardiovascular risks of these drugs. To begin, it may be helpful to understand how they work. (If this information is too technical or just more than you wanted to know, feel free to skip ahead to “Is Celebrex right for you?”)

Some background: how NSAIDs work

NSAIDs (pronounced "en-seds") are used to decrease pain, inflammation and fever. Because inflammation contributes to pain, their anti-inflammatory effect offers extra relief.

Traditional NSAIDs have been on the market for a long time. The drugs you’ve been taking – first Bextra and now Celebrex – belong to a newer category called “cox-2 selective NSAIDs.”

“Traditional” NSAIDs: These are prescription and non-prescription medicines found in many a medicine chest. Common examples are aspirin (the classic Bayer or St. Josephs), ibuprofen (Motrin, Nuprin), naproxen (Aleve), ketoprofen (Orudis, Actron) and etodolac (Lodine). Acetaminophen, or Tylenol, is not on this list because it is not an anti-inflammatory. While aspirin is on the list, it has some heart-protective effects that are different from the rest of the group.

Traditional nonsteroidal anti-inflammatories reduce pain and inflammation by blocking the actions of two enzymes – cox-1 and cox-2 for short. These enzymes help produce prostaglandins, a multi-tasking fatty acid.

Cox-2 enzymes block the prostaglandins that set off pain-causing inflammation after injury or infection.

Cox-1 enzymes squelch prostaglandins that protect the lining of the stomach and digestive tract from acids. They also block prostaglandins involved in blood clotting.

The dilemma that traditional NSAIDs have always presented is this: By blocking cox-2, they are very effective at relieving pain and inflammation; but in blocking stomach-protecting cox-1, as well, they leave the digestive system more vulnerable to stomach pain, nausea, heartburn, bloating, peptic ulcers and serious gastrointestinal bleeding.

"Selective" NSAIDs: The advantage of the selective NSAIDs (Celebrex, Vioxx and Bextra) is that they “selectively” focus on blocking only the cox-2 enzyme. Thus they decrease inflammation (that's good) but have little impact on the digestive system and blood clotting (also good).

These newer NSAIDs were a welcome alternative for patients who either couldn't tolerate the traditional NSAIDs or who were at high risk of gastrointestinal complications, including stomach bleeding, gastric (stomach) ulcers or irritation of the colon or small bowel.

The cardiovascular risks of NSAIDs

The entire class of NSAIDs made big news in September 2004 when the manufacturer of Vioxx voluntarily withdrew its product from the market. A cancer prevention study involving Vioxx had found an increased risk of "serious cardiovascular events" – mainly heart attack and stroke – in patients taking the drug. The risk was small, but it rose as patients took higher doses and/or took it for longer periods of time.

The withdrawal of Vioxx prompted the Food and Drug Administration to take a closer look at the data on all NSAIDs, and the following April, Bextra was withdrawn from the market as well, at the FDA's request. The FDA was concerned about a Bextra study showing that cardiac bypass surgery patients who took high doses of Bextra after their surgery were at higher risk of cardiac problems. The FDA wanted more information about Bextra's general cardiovascular safety, and expressed additional concern about Bextra’s association with an increased number of rare but potentially fatal skin reactions.

Celebrex is the only selective NSAID that remains available. Only one Celebrex study has shown an increased risk of heart attack and stroke, and in that study (a colon cancer prevention study) participants took either 400 mg or 800 mg a day; 800 mg is never prescribed for arthritis. At a typical dosage of 200 mg a day, Celebrex has not been associated with a significantly increased risk of cardiovascular events. 

Some studies have raised questions about whether the traditional NSAIDs (except for aspirin and naproxen) also increase cardiac risks when used at high doses, long term. The scientific data are murky – many previous studies showed they had no effect on the risk of heart attack and stroke, and some showed a decreased risk. Until we know more, however, the FDA is mandating that labeling for every NSAID – nonprescription or prescription, traditional or selective – must warn of the potential for cardiovascular risks. The FDA's reasoning: Although traditional NSAIDs have been used for many years, they have not been subjected to rigorous long-term studies, such as the Vioxx multi-year cancer prevention trial that raised the first concerns about heart attack and stroke. A practical problem in conducting arthritis studies is that arthritis patients cannot be put on a placebo long term. However, scientists are continuing to pursue a number of research avenues.

Is Celebrex right for you?

In the FDA’s latest guidelines, released in spring 2005, Celebrex is approved for patients with rheumatoid arthritis, at a starting dose of 100 to 200 mg a day, and up to a maximum daily dose of 400 mg. (It takes about a two-week trial to tell if the dose is effective.) Celebrex also is approved for osteoarthritis, at 200 mg a day. The drug now must be packaged with a medication guide and more-specific patient information about the drug’s risks.

Determining whether Celebrex is right for you depends on your health history. For now, I reserve Celebrex for more-severe cases of arthritis in patients who are at low risk for heart disease and at high risk for gastrointestinal complications.

Are you at high risk for gastrointestinal problems?

According to the American College of Rheumatology, the following groups are at high risk for gastrointestinal complications:

  • People over age 65 or 70 (studies differ)
  • Women
  • People who take prednisone or Coumadin
  • People who have a history of ulcers or gastrointestinal bleeding

Celebrex, like other NSAIDs, does add some risk of gastrointestinal bleeding. However, because cox-2 drugs do not affect clotting, scientists feel they are safer choices for patients who are inclined to bleed, such as those on Coumadin and, in some cases, those who take low-dose aspirin. 

In a recent study, patients swallowed small cameras tucked inside capsules. The cameras tracked their digestive tracts. The results indicated that Celebrex caused fewer small ulcers in the intestines than traditional NSAIDs. However, this information needs to be verified and confirmed by additional, larger studies.

Two older, traditional NSAIDs, Salsalate and Trilisate, appear to be easier on the stomach than the other traditional NSAIDs and do not affect bleeding. These are less expensive than Celebrex, and for some patients, they offer another treatment option.

Some high-risk patients can take traditional NSAIDs in combination with drugs that protect the stomach and help prevent ulcers. These anti-ulcer medications, called proton pump inhibitors, include Prilosec, Prevacid, Aciphex, Nexium and Protonix.

Although proton pump inhibitors do not work for all patients, they do protect against the damaging effects of NSAIDs more effectively than food, antacids (Tums, Maalox, Myltanta) or traditional anti-ulcer medicines, called histamine blockers (Tagamet, Zantac).

When gastrointestinal problems are not a high risk

If you are not at high risk of gastrointestinal bleeding, you might discuss other choices with your physician. Naproxen (Aleve), at 1,000 mg to 1,500 mg a day, is approved for arthritis pain and inflammation. I don’t see aspirin as a realistic option, because the amount that an arthritis patient would need to take would incur far too many side effects.

Communication: the best medicine

My patients need relief from chronic pain, so we discuss their personal health profile, lifestyle, and the risks and benefits of various therapies. I ask about high blood pressure (all NSAIDs have the potential to increase blood pressure), smoking, elevated cholesterol, drug allergies, gastrointestinal problems, diabetes, prior heart attack or stroke, other medicines and family history before prescribing any medication, including NSAIDs.

Patients generally understand that no medicine is perfect, and they weigh that against the disease that needs treating.

You may also consider non-drug options such as acupuncture, chiropractic, massage and physical therapy. I coordinate care with physical therapists who draw upon such complementary techniques as acupressure, ultrasound, manipulation, exercise, splints, and nerve stimulation along Chinese pain points. My main caution is that complementary therapies should be used in addition to medical therapy for arthritis, not in place of it. Medical treatment is especially important for rheumatoid arthritis, a serious autoimmune disease that, if untreated, attacks the joints, muscles, tendons and lungs and can shorten a patient's life.

A proper diet also can have therapeutic benefits. Certain types of fish (especially salmon), ground flaxseed and primrose oil may have an anti-inflammatory effect (if taking supplements, however, note that in clinical and laboratory tests, the effective doses vary widely).

I also recommend a good multi-vitamin (Centrum, One-a-Day) and a calcium-vitamin D supplement. Post-menopausal women, patients on corticosteroids and patients with low bone density or osteoporosis should consume 1,200 mg to 1,500 mg daily of calcium and 400 IU to 800 IU of vitamin D.

Some patients with osteoarthritis report increased comfort when taking glucosamine-chondroitin supplements. I suggest they try it for three months and continue if it helps them. The results of a large glucosamine study are expected in 2006, so we will have more guidance then.

I hope you will have a thorough discussion with your physician about all arthritis therapies so that together, you can make the best choices for you.

Learn more about the FDA's position on NSAIDS.

June 2005