Treating Osteoarthritis and Pain: The Non-Steroidal Anti-Inflammatory Drugs Comparing Effectiveness, Safety, and Price

Transcription

1 Treating Osteoarthritis and Pain: The Non-Steroidal Anti-Inflammatory Drugs Comparing Effectiveness, Safety, and Price

2 Our Recommendations Costs for non-steroidal anti-inflammatory drugs (NSAIDs) the most frequently used medicines to treat arthritis and mild to moderate pain vary from $24 to $306 a month. This report compares the effectiveness, safety and cost of the many NSAIDs available in the U.S. These include the drugs ibuprofen and naproxen and the heavily advertised celecoxib (Celebrex) and valdecoxib (Bextra), which may be overused. If you must take NSAIDs regularly, our report shows how you could save $180 a month ($2,160 a year) or more by choosing less expensive medicines. Since individual needs vary, use this information to talk with your doctor about what s right for you. Your doctor may not be aware of price differences between medicines. Also talk with your doctor about the possible risks: All NSAIDs can have dangerous side effects, especially stomach ulcers and bleeding. Taking effectiveness, safety and cost into account, we have chosen two Consumer Reports Best Buy Drugs in this category: Generic ibuprofen at a dose of 400mg, 600mg or 800mg three times a day costing an average $24 to $30 a month. Generic salsalate at a dose of 750mg three or four times a day costing an average $24 a month. These medicines are much less expensive than other NSAIDs and are as effective as any of them, including Celebrex and Bextra. Some special considerations: If you have drug coverage, talk with you doctor about finding the NSAID that has the lowest out-of-pocket cost under your insurance plan. Many generics are available. If you have had a stomach ulcer or bleeding, or are at high risk of either, you may want to avoid using NSAIDs. They raise the risk, which increases with age. If you are at risk of heart attack or stroke, talk with your doctor about potential safety concerns with Celebrex and Bextra. NSAIDs can interact with other medicines to cause serious side effects. If your doctor prescribes an NSAID, tell him or her about any other medicine you are taking. 2 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

3 Welcome This report on the pain relievers called NSAIDs (pronounced en-sayds) which stands for non-steroidal anti-inflammatory drugs" is part of a Consumers Union and Consumer Reports project to help you find safe, effective medicines that give you the most value for your health care dollar. To learn more about the project and other drugs we ve evaluated, go to NSAIDs are used by tens of millions of Americans everyday to treat osteoarthritis and mild to moderate pain. The most commonly used, starting with those also available as over-the-counter medicines, are: Generic Name Acetylated Salicylates Ibuprofen Ketoprofen Naproxen Celecoxib Diclofenac Diflunisal Etodolac Fenoprofen Flurbiprofen Indomethacin Meclofenamate Meloxicam Nabumetone Nonacetylated Salicylates Oxaprozin Piroxicam Sulindac Tolmetin Valdecoxib Brand Name(s) Aspirin, Bayer, Bufferin Advil, Motrin, Nuprin Orudis, Oruvail Aleve, Anaprox, Naprosyn, Neprelan Celebrex Voltaren, Cataflam Dolobid Lodine Nalfon Ansaid Indocin, Indameth Meclomen Mobic Relafen Salsalate, Mono-Gesic, Salsitab, Amigesic, Anaflex Daypro Feldene Clinoril Tolectin Bextra Other over-the-counter and prescription medicines are available to treat osteoarthritis and mild to moderate pain. Acetaminophen (Tylenol, Datril) is the one that most people use. Indeed, many doctors recommend that you try acetaminophen for mild pain before an NSAID and only consider an NSAID if acetaminophen doesn t work for you. Acetaminophen is only slightly less effective than the NSAIDs, and is generally safer. Also, talk to your doctor about using skin creams and glucosamine and chondroitin supplements to relieve arthritis pain. While this report focuses on the use of NSAIDs to treat osteoarthritis, you ll also find it helpful if you use these drugs to relieve everyday aches and pains. The report is based on a comprehensive expert analysis of the medical evidence. There s more information on page 13 and at about how we conducted our evaluation. This report was last updated in December Non-Steroidal Anti-Inflammatory Drugs Consumer Reports Best Buy Drugs 3

4 What Are NSAIDs and Who Needs Them? NSAIDs are the most commonly used medicines to treat mild to moderate pain from arthritis, bursitis, tendonitis, and sprains, as well as premenstrual cramps, headache, back ache, and minor injuries. They are also used to reduce fever. NSAIDs come in both prescription and nonprescription forms. NSAIDs are the most frequently prescribed treatment for osteoarthritis, a degenerative joint disease that causes pain, stiffness and immobility. The drugs don t cure the disease, but they can relieve its symptoms. Your doctor is most likely to consider an NSAID if you have osteoarthritis symptoms that aren t helped by exercise, other non-drug treatments, or Tylenol. About 21 million people in the U.S. have osteoarthritis. But almost everyone older than 60 or so has some of the same symptoms, which generally worsen as you get older. One of the best ways to ward off the pain, stiffness and joint "creakiness" of osteoarthritis and aging is regular exercise, stretching and muscle strengthening. In some case, keeping active and limber can eliminate or sharply reduce the need to take medicines. Be careful, however: if you already have moderate to severe osteoarthritis, strenuous activity can stress weakened joints. Such activity should be undertaken with the advice of a doctor or physical therapist. Don t confuse osteoarthritis with rheumatoid arthritis. The latter is an immune system disease that usually strikes people between the ages of 30 and 50, and causes inflammation of the joints that gets worse over time. NSAIDs are often used to relieve the pain and inflammation associated with rheumatoid arthritis. But the underlying disease often needs treatment with other kinds of drugs. NSAIDs work primarily by blocking the body s production of hormones called prostaglandins. These chemicals help cause pain, inflammation, fever and muscle cramps and aches. All of the NSAIDs work in much the same way as aspirin, which has been used for more than 2,000 years to treat pain. At low doses, the NSAIDs work essentially as pain relievers. At higher doses, they can reduce the body s inflammatory response to tissue damage, as well as relieve pain. Most NSAIDs block two different enzymes, called Cox-1 and Cox-2, that the body uses to make prostaglandins. (Cox stands for cyclo-oxygenase). This can cause problems because prostaglandins produced by the Cox-1 enzyme actually protect the lining of the stomach from acid. So blocking their production leads to an increase in the risk of stomach bleeding and ulcers. Some people have an especially high risk of this problem but it s hard to tell in advance who they are. About 14,000 to 16,000 people die each year as a result of gastrointestinal bleeding caused by NSAIDs. Two types of NSAIDs are now available. One is called the nonselective" NSAIDs; and the second type is awkwardly called the selective" Cox-2 inhibitors, or just the Cox-2s" for short. Much has been made of the difference between these two types. Put simply, the Cox-2 drugs mostly affect that one enzyme and block the Cox-1 enzyme far less. That means they should cause less damage to the stomach than nonselective NSAIDs. For people who are susceptible to stomach bleeding and ulcers about 5 percent of the population this advantage is quite important. But the Cox-2 drugs have recently become quite controversial. While their main advantage is in treating people at higher risk for stomach problems, they are now used by many more people who do not have that risk. Because the risk of stomach bleeding and ulcers can be difficult to assess, many doctors prescribe Cox- 2s to be cautious. But their use has also soared because they have been heavily promoted to doctors and advertised to consumers. In addition, one of the best selling Cox-2s a drug called Vioxx (rofecoxib) was taken off the market in September 2004 after it was linked to a higher risk of heart attacks and strokes. Two Cox-2s remain on the market, celecoxib (Celebrex) and valdecoxib (Bextra). The company that make these two drugs, as well as U.S. health authorities, are now re-evaluating whether the medicines pose similar risks to the heart that could outweigh their benefits. Those benefits are in question, too. Studies have not shown definitively that using Celebrex or Bextra, 4 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

5 rather than other NSAIDs, lowers the risk of the most dangerous kind of gastrointestinal (GI) ulcers and bleeding. If you are at higher risk of heart attack or stroke for example, if you have high cholesterol, diabetes or high blood pressure talk with your doctor about how to weigh the risks and benefits of taking different kinds of NSAIDs. Even as concern about the heart risks of Cox-2 drugs has been raised, other NSAIDs may actually lower the risk of heart attack and stroke. This benefit has been well established for the oldest and best known NSAID, aspirin and it s the reason doctors now advise all people at higher risk for heart attack to take a quarter to half an aspirin tablet everyday. There s no good evidence yet, however, on whether NSAIDS besides aspirin can also prevent heart attacks, so doctors agree that it is premature to prescribe them for this purpose. Choosing an NSAID Our Studies show that all the NSAIDs ease the pain and other symptoms of osteoarthritis. At equivalent doses, their effectiveness is essentially the same. That includes the newer Cox-2 drugs Celebrex and Bextra. But the NSAIDs differ greatly in price with some nonprescription and generic versions costing as little as $24 to $30 a month and expensive brands costing $200 or more monthly for the typically prescribed dose. To choose the best drug and dose, you and your doctor should consider: The severity of your pain, joint stiffness, and other symptoms Your history and risk of stomach bleeding and ulcers Your history and risk of heart attack or stroke The drug s cost and your insurance coverage The drug s possible interaction with other medications you take Taking effectiveness, safety, and cost into account, we have chosen two prescription NSAIDs as the Consumer Reports Best Buy Drugs to consider first. They are: Generic ibuprofen, by prescription, at a dose of 400mg, 600mg or 800mg three times a day. The 400mg dose (three times a day) costs an average of $24 a month. The 600mg and 800mg dose (three a day) costs an average $30 a month. Picks Generic salsalate at a dose of 750mg three or four times a day. This dose three times a day costs an average $24 a month. Four times a day costs $32. These two medicines are substantially less expensive than other NSAIDs and are as effective as any of them, including Celebrex and Bextra. As you can see in Table 2 on pages 8 and 9, nonprescription ibuprofen (Advil) costs about the same ($24 a month) when taken at doses equal to prescription strength ibuprofen. But if you need to regularly take such high doses of this drug, you should be under a doctor s care instead of treating yourself, primarily because of safety considerations. If you have insurance coverage, there s another reason to take prescription ibuprofen, or other prescription generic NSAIDs: you will likely save money. They will cost you $5 to $10 per month, as a co-pay, under most insurance plans. If you get your medicine by mail order, your cost could be even lower. Some brand-name NSAIDs may cost two to three times as much as generic ones, and may require a larger copayment. As you can see in Table 2, many brand-name NSAIDs have a generic equivalent, so there s little reason in these cases to get a prescription for the more expensive brand medicine. If you do not have health insurance or drug coverage, and you take pain medicines on a regular basis for osteoarthritis, we recommend that you talk to your doctor about using generic ibuprofen or salsalate. However, if you are uninsured and need to take an NSAID only every once in a while for example, if your symptoms Non-Steroidal Anti-Inflammatory Drugs Consumer Reports Best Buy Drugs 5

6 Table 1. Summary of NSAID Options in Treating Osteoarthritis Risks - Low GI risk 1 or none - Low heart or stroke risk - GI risk - Low heart or stroke risk - Heart or stroke risk - Low GI risk - Heart or stroke risk - GI risk Options - Generic ibuprofen or salsalate - NSAID with lowest out-of-pocket cost - Acetaminophen (Tylenol) (Consider trying first) - Lowest possible dose of an older NSAID plus a stomach acid reducer - Salsalate - A Cox-2 drug (Celebrex, Bextra) - Acetaminophen (Tylenol) (Consider trying first) - Older NSAID but not if taking aspirin - Aspirin at higher dose (option: with stomach acid reducer) - Acetaminophen (Tylenol) - Older NSAID with a stomach acid reducer - Aspirin specifically with a stomach acid reducer - Acetaminophen (Tylenol) for pain plus low dose aspirin for heart. Stay alert to signs of ulcer. 1. GI stands for Gastrointestinal are mild you can probably get the pain relief you need by using one of these over-the-counter drugs: Aspirin (Bayer, Bufferin), which typically comes in 325mg tablets that can cost less than a penny each for uncoated forms Naproxen (Aleve), which typically comes in 220mg tablets that cost about 13 cents each Ibuprofen (Advil, Motrin IB, Nuprin), which typically comes in 200mg tablets that cost about 14 cents each Ketoprofen (Orudis-KT), which typically comes in 12.5mg tablets that cost about 14 cents each These over-the-counter medicines are as effective as prescription drugs when taken in doses equal to prescription medicines. If you think you need more pain relief than you are getting from your over-the-counter NSAID, talk with your doctor about increasing your dose of those drugs or trying a prescription NSAID. Indeed, the dose you take of an NSAID is an important factor in the degree of symptom relief you get and your risk of complications. As you can see in Table 2 on pages 8-9, the NSAIDs come in a variety of doses (and we haven t even listed them all). Talk with your doctor about the dose level that is best for you and, if you switch NSAIDs, which dose of the new one is equivalent to what you were taking. No matter what dose you take, it is important to remember that regular (and especially every day) use of NSAIDs prescription or nonprescription can lead to complications. That is why the instructions that accompany all nonprescription NSAIDs say not to use them regularly for more than a few days without consulting a physician. Unfortunately, that advice is widely ignored. If you take a nonprescription NSAID like aspirin, Advil or Aleve several times a week (or more) because of chronic pain, stiffness or to prevent sports injuries or muscle soreness after sports activities, you should see a doctor to discuss your treatment. If You Are at Risk for Ulcers or GI Bleeding To find the NSAID drug and dose that are right for you, your doctor should assess your risk of stomach ulcer or intestinal bleeding. If you are at risk, your doctor and you have a number of options. You can: 6 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

7 Avoid NSAIDs and take acetaminophen (Tylenol) Try an older NSAID along with a stomach acid reducer such as omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium) or misoprostol (Cytotec) Try either Celebrex or Bextra Try generic salsalate If You Avoid NSAIDs and Take Acetaminophen The best way to avoid the risk of dangerous ulcers altogether is to stop taking any NSAID. Many doctors recommend that people with osteoarthritis try acetaminophen first, before an NSAID, because this pain reliever poses no risk of stomach problems. People who have had ulcers or are at risk for them would be even more strongly urged to talk with their doctor about this option. If You Try an NSAID With an Acid Reducer Acid reducers lower the incidence of ulcers and GI bleeding in people taking NSAIDs. And this combo has become a commonly prescribed treatment. But it is not yet proven whether the combo significantly reduces the risk of the most dangerous kind of ulcers and GI bleeding, and it certainly does not eliminate the risk completely. Also, you will have to pay for another medicine. One nonprescription acid reducer is relatively inexpensive - over-the-counter Prilosec. This medicine costs an average of $24 a month and is a Consumer Reports Best Buy Drug in the category of medicines called proton pump inhibitors (PPIs). (Our evaluation of this category is available at If You Try Celebrex or Bextra Celebrex and Bextra carry a lower risk of some types of stomach ulcers if you have to take an NSAID. But studies have not shown definitively whether these drugs lower the risk of the most dangerous kind of ulcers and GI bleeding. Some doctors may be cautious about prescribing Celebrex and Bextra until the evidence is in from studies now underway after the removal of Vioxx from the market. Vioxx was linked to a higher risk of heart attack and stroke. If You Try Salsalate Salsalate has been around for over 20 years. Studies conducted in the 1980s and early 1990s suggest that it may cause less stomach bleeding than some of the other NSAIDs available then. However, here too, studies have not shown definitively whether salsalate lowers the risk of the most dangerous kind of ulcers and GI bleeding. In addition, no studies have examined salsalate s affect on heart disease risk and salsalate should not replace aspirin for those at risk of heart disease. (See below.) Salsalate can also cause ringing in the ears more than other NSAIDs do. If your doctor and you decide that you must use an NSAID, you can also reduce the risk of stomach ulcer and GI bleeding by: Taking the lowest dose possible that gives you symptom relief Taking the medicine only when you need to Being especially alert to the signs of an ulcer or GI bleeding, such as burning stomach pain, blood in your stool, or bowel movements that are black and tarry. If You Have Had a Heart Attack or Stroke or Are at High Risk of Either If you fall in this category and take or need an NSAID, talk with your doctor about whether Celebrex or Bextra may be risky for you. Your doctor may suggest waiting until further research or FDA evaluation establishes their long-term safety. For now an older NSAID may be a better choice. Also talk to your doctor if, like millions of Americans, you are already taking daily low-dose aspirin to reduce your risk of a heart attack or stroke. It turns out that aspirin plus another NSAID is a potent combination: Aspirin and older NSAIDs taken together increase the risk of ulcers and GI bleeding. Some NSAIDs reduce aspirin s heart-protective affect when the two medicines are taken together. Diclofenac (Voltaren) may be an option that does not. Cox-2s plus aspirin wipe out the stomach ulcer advantage of Cox-2s. If you are taking aspirin already for heart protection, talk with your doctor about increasing the dose to treat your pain and adding an acid reducing drug such as omeprazole (Prilosec OTC). Non-Steroidal Anti-Inflammatory Drugs Consumer Reports Best Buy Drugs 7

8 Table 2. NSAID Cost Comparison Generic Name Brand Name(s) 1 Dose and Frequency of Use 2 Average Cost for a Month s Supply 3 Celecoxib Celebrex 100mg two a day $130 Celecoxib Celebrex 200mg two a day $212 Diclofenac Voltaren, Cataflam 50mg three a day $192 Diclofenac Generic 50mg three a day $63 Diclofenac Long-Acting Voltaren-XR 100mg one a day $159 Diclofenac Long Acting Generic 100mg one a day $73 Diflunisal Dolobid 500mg two a day $106 Diflunisal Generic 500mg two a day $72 Diflunisal Dolobid 250mg two a day $84 Diflunisal Generic 250mg two a day $46 Etodolac Lodine 200mg three a day $150 Etodolac Generic 200mg three a day $81 Etodolac Lodine 400mg three a day $177 Etodolac Generic 400mg three a day $75 Etodolac Sustained Release Lodine XL 600mg one a day $103 Etodolac Sustained Release Generic 600mg one a day $80 Fenoprofen Nalfon 300mg three a day $57 Fenoprofen Generic 600mg three a day $39 Flurbiprofen Ansaid 100mg three a day $273 Flurbiprofen Generic 100mg three a day $63 Ibuprofen Motrin 400mg three a day $30 Ibuprofen Generic 400mg three a day $24 Ibuprofen Advil 4 400mg three a day (total of six pills) $24 Ibuprofen Motrin 600mg three a day $39 Ibuprofen Ibu 600mg three a day $30 Ibuprofen Generic 600mg three a day $30 Ibuprofen Motrin 800mg three a day $51 Ibuprofen Ibu 800mg three a day $33 Ibuprofen Ibu-Tab 800mg three a day $30 Ibuprofen Generic 800mg three a day $30 Indomethacin Indocin 25mg three a day $66 Indomethacin Generic 25mg three a day $30 Indomethacin Indocin 50mg three a day $105 Indomethacin Generic 50mg three a day $39 Indomethacin Indocin SR 75mg two a day $150 Indomethacin Generic 75mg two a day $68 Ketoprofen Orudis 75mg two a day $84 8 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

9 Table 2. NSAID Cost Comparison (continued) Generic Name Brand Name(s) 1 Dose and Frequency of Use 2 Average Cost for a Month s Supply 3 Ketoprofen Generic 75mg two a day $48 Ketoprofen Orudis KT mg twelve a day $51 Meclofenamate Generic 100mg three a day $306 Meloxicam Mobic 7.5mg one a day $104 Meloxicam Mobic 15mg one a day $142 Nabumetone Relafen 500mg two a day $113 Nabumetone Generic 500mg two a day $70 Nabumetone Relafen 750mg two a day $136 Nabumetone Generic 750mg two a day $84 Naproxen Naprosyn 375mg three a day $150 Naproxen Generic 375mg three a day $42 Naproxen Naprosyn 500mg three a day $189 Naproxen Generic 500mg three a day $48 Naproxen Aleve 4 440mg three a day (total of six pills) $24 Oxaprozin Daypro 600mg one a day $74 Oxaprozin Generic 600mg one a day $34 Oxaprozin Daypro 600mg three a day $222 Oxaprozin Generic 600mg three a day $102 Piroxicam Feldene 20mg one a day $108 Piroxicam Generic 20mg one a day $31 Salsalate Disalcid 750mg three a day $87 Salsalate Generic 750mg three a day $24 Salsalate Generic 750mg four a day $32 Sulindac Clinoril 150mg two a day $74 Sulindac Generic 150mg two a day $40 Sulindac Clinoril 200mg two a day $92 Sulindac Generic 200mg two a day $40 Tolmetin Generic 200mg three a day $57 Tolmetin Tolectin 400mg three a day $171 Tolmetin Generic 400mg three a day $93 Valdecoxib Bextra 10mg one a day $113 Valdecoxib Bextra 20mg one a day $ "Generic" indicates drug sold by generic name. Most brand NSAIDs have generic equivalents. 2. As commonly recommended or prescribed. NSAIDs come in a variety of recommended doses. Talk with your doctor about the equivalency of dosing between different NSAIDs. 3. Prices reflect nationwide retail average costs for September 2004, rounded to nearest dollar; data provided by NDCHealth, a healthcare information company. 4. This is a nonprescription (over-the-counter) drug. Non-Steroidal Anti-Inflammatory Drugs Consumer Reports Best Buy Drugs 9

10 The Evidence This section presents more information on the effectiveness and safety of the NSAIDs. Studies show the NSAIDs to be effective pain relievers. But they have risks. All NSAIDs increase the risk of bleeding and ulcers in the stomach, including the Cox-2 drugs Celebrex and Bextra. NSAIDs also have other risks, such as increasing blood pressure, causing fluid retention, and reducing kidney function. Studies have assessed the effectiveness and benefits of NSAIDs based on three criteria: How well they reduce pain and swelling and improve function and well being The risk of serious gastrointestinal (GI) bleeding and ulcers The frequency and severity of other risks, such as increasing the risk of heart attack, increasing blood pressure, causing fluid retention, and reducing kidney function How Effective Are NSAIDs? In general, the NSAIDs reduce pain by an average of 50%. And studies show they enhance mobility in about 60% of people with osteoarthritis. The degree of pain relief you get will depend primarily on the intensity of your pain. But subjective factors also come into play. For example, some people are more tolerant of pain than others. Also, some people may respond to some NSAID drugs better than others because of genetic differences. Hundreds of studies have been done on NSAIDs, with many comparing one NSAID to another at comparable doses. Overall, the differences between them appear to be negligible and study findings do not consistently show any one NSAID to be better than another for pain relief. That includes the Cox-2 drugs Celebrex and Bextra. Studies have shown, for example, that typically used doses of ibuprofen, naproxen and diclofenac are just as effective for relieving pain as Celebrex. NSAIDs may be less effective against some types of joint pain. For example, a recent analysis found NSAIDs of marginal benefit in relieving pain in people with osteoarthritis of the knee. How Safe Are NSAIDs? As discussed throughout this report, NSAIDs can cause life-threatening GI bleeding, usually from the stomach. The risk increases with age. As shown in Table 3, a person who is over 75 and takes an NSAID has about a one in 110 chance of having a GI bleed, and a one in 647 chance of dying from that complication. Table 3. Serious Risks Associated With NSAIDs Age Risk of GI bleeding each year Risk of dying from GI bleeding each year Risk in any one year is: in in 12, in in 3, in in 3,353 >75 1 in in 647 When applied to the population as a whole, NSAIDrelated deaths are substantial. As shown in Table 4 on page 11, the death rate is higher than that found from cervical cancer, asthma or malignant melanoma, for example. As mentioned, the Cox-2 drugs cause fewer ulcers than older NSAIDs. But it turns out that the kind of ulcer is important. Specifically, studies show that the Cox-2s cause fewer endoscopic ulcers." These are ulcers that usually cause no symptoms or actual bleeding and are found only by performing an endoscopy. This type of ulcer is not as dangerous as ulcers that seriously erode the lining of the stomach and lead to bleeding or actual holes in the stomach. The only NSAID ever proven to cause fewer serious ulcer complications was Vioxx, the Cox-2 drug that was removed from the market in October Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

11 A lower risk of ulcers is assumed for Celebrex and Bextra, the remaining Cox-2 drugs. But the exact magnitude of the risk associated with either drug compared to older NSAIDs is not known. One major study compared Celebrex with two other NSAIDs, ibuprofen and diclofenac. Overall Celebrex was not less likely to cause serious ulcer complications. However, some of the patients in this study also took aspirin. In those who were not taking aspirin, Celebrex was less likely to cause serious ulcer complications than ibuprofen but was equivalent to diclofenac. Bextra has not yet been conclusively proven to have a lower risk of serious GI complications than older NSAIDs. Heart Attacks and Strokes Vioxx s removal from the market has triggered an intensive reevaluation of Celebrex and Bextra. The company that makes Bextra has announced that the drug caused an increased rate of heart attacks in people who had coronary bypass surgery, and is not recommended for such patients. The same company makes Celebrex and has launched new studies of that drug s association with heart disease. Studies of Celebrex to date are simply inconclusive. While several have not linked the drug to an increased risk of heart attack compared with people taking other NSAIDs, one study did. There is no evidence that older NSAIDs increase the risk of having a heart attack. Aspirin, of course, has been proven to help prevent heart attacks. But whether this effect applies to other older NSAIDs is not yet clear. That question has been examined only in small clinical trials, which have suggested some protective affect. To further complicate things, ibuprofen and some other NSAIDs can interfere with aspirin s heart-protective actions when the drugs are taken together. This interaction can be reduced if the drugs are taken two hours or more apart. The Cox-2 drugs and diclofenac (Voltaren and Cataflam) do not cause this interaction. Hypertension, Heart Failure, and Kidney Problems All the NSAIDs can aggravate high blood pressure. NSAIDs cause fluid retention, which can lead to slight weight gain or swollen legs in healthy individuals. In people who have a weak heart" (left ventricular dysfunction), fluid retention due to NSAIDs can cause congestive heart failure. NSAIDs also reduce kidney function in some individuals, especially those who already have kidney disease from diabetes or other causes. The risk of these problems is similar for different NSAIDs, including the Cox-2s. Tolerability Table 4. NSAIDs Related Deaths Compared to Other Diseases Cervical Cancer Asthma Malignant Melanoma GI adverse effects Leukemia Diabetes HIV All the NSAIDs can cause other side effects, including stomach upset, abdominal pain and diarrhea. Their frequency is about the same no matter which NSAID you take. About one in five people taking prescription doses of ibuprofen, naproxen, or diclofenac, for example, have one of these side effects. Some studies indicate a higher rate of such problems with indomethacin and a lower rate with Celebrex. However, most people taking the older NSAIDs do not stop taking the medicines because of side effects. The NSAIDs can also cause skin rashes, but these are rare. Bextra has been linked to a type of serious rash that has led to hospitalizations and even death in a few people. Anyone taking Bextra should consult a doctor immediately if a skin rash appears. Age, Race, and Gender Differences Death Rate (per 100,000 people) Age is an important factor when considering NSAID treatment, especially long term. The risk of GI bleeding and stomach ulcers increases with age, as seen in Table 3 on page 10. The older you are the more cautious your doctor may be in treating you with NSAIDs for long periods. Some doctors now routinely prescribe a stomach acid reducer to all people aged 65 and over taking an NSAID. Non-Steroidal Anti-Inflammatory Drugs Consumer Reports Best Buy Drugs 11

12 Talking With Your Doctor It s important for you to know that the information we present here is not meant to substitute for a doctor s judgment. But we hope it will help your doctor and you arrive at a decision about which NSAID and NSAID dose is best for you, and which gives you the most value for your health care dollar. Bear in mind that many people are reluctant to discuss the cost of medicines with their doctors and that studies show doctors do not routinely take price into account when prescribing medicines. Unless you bring it up, your doctors may assume that cost is not a factor for you. Many people (including physicians) also believe that newer drugs are always or almost always better. While that s a natural assumption to make, the fact is that it s not true. Studies consistently show that many older medicines are as good as, and in some cases better than, newer medicines. Think of them as "tried and true," particularly when it comes to their safety record. Newer drugs have not yet met the test of time, and unexpected problems can and do crop up once they hit the market. Of course, some newer prescription drugs are indeed more effective and safer. Talk with your doctor about the pluses and minuses of newer versus older medicines, including generic drugs. Prescription medicines go "generic" when a company s patents on a drug lapse, usually after about 12 to 15 years. At that point, other companies can make and sell the drug. Generics are almost always much less expensive than newer brand name medicines, but they are not lesser quality drugs. Indeed, most generics remain useful medicines even many years after first being marketed. That is why today about 47% of all prescriptions in the U.S. are for generics. Another important issue to talk with your doctor about is keeping a record of the drugs you are taking. There are several reasons for this: First, if you see several doctors, each may not be aware of medicines the others have prescribed. Second, since people differ in their response to medications, it is very common for doctors today to prescribe several medicines before finding one that works well or best. Third, many people take several prescription medications, non-prescription drugs and dietary supplements at the same time. These can interact in ways that can either reduce the benefit you get from the drug, or be dangerous. And fourth, the names of prescription drugs both generic and brand are often hard to pronounce and remember. For all these reasons, it s important to keep a written list of all the drugs and supplements you are taking, and to periodically review this list with your doctors. Always be sure, too, that you understand the dose of the medicine being prescribed for you and how many pills you are expected to take each day. Your doctor should tell you this information. When you fill a prescription at the pharmacy, or if you get it by mail, you may want to check to see that the dose and the number of pills per day on the pill bottle match the amounts that your doctor told you. 12 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

13 How We Picked the NSAIDs Our evaluation is based on an independent scientific review of the evidence on the effectiveness, safety and adverse effects of the NSAIDs. A team of physicians and researchers at Oregon Health & Science University Evidence-based Practice Center conducted the analysis as part of the Drug Effectiveness Review Project, or DERP. DERP is a first-of-its-kind 12-state initiative to evaluate the comparative effectiveness and safety of hundreds of prescription drugs. A synopsis of DERP s analysis of the NSAIDs forms the basis for this report. A consultant to Consumer Reports Best Buy Drugs is also a member of the Oregon-based research team, which has no financial interest in any pharmaceutical company or product. The full DERP review of NSAIDs is available at (It is a long and technical document written for physicians.) The drug costs we cite were obtained from a healthcare information company which tracks the sales of prescription drugs in the U.S. Prices for a drug can vary quite widely, even within a single city or town. All the prices in this report are national averages based on sales of prescription drugs in retail outlets. They reflect the cash price paid for a month s supply of each drug in September Consumers Union and Consumer Reports selected the Best Buy Drugs using the following criteria. The drug (and dose) had to: Be approved by the FDA for treating at least one form of arthritis. Have a safety record equal to or better than other NSAIDs. Have an average price for a 30-day supply that is at least 25% lower than the most costly NSAID meeting the first two criteria. The Consumers Reports Best Buy Drugs methodology is described in more detail in the Methods section at About Us Consumers Union, publisher of Consumer Reports magazine, is an independent and nonprofit organization whose mission since 1936 has been to provide consumers with unbiased information on goods and services and to create a fair marketplace. Its website is The magazine's website is Consumer Reports Best Buy Drugs is a public education project administered by Consumers Union. Two outside sources of generous funding made the project possible. They are a major grant from the Engelberg Foundation, a private philanthropy, and a supporting grant from the National Library of Medicine, part of the National Institutes of Health. A more detailed explanation of the project is available at We followed a rigorous editorial process to ensure that the information in this report and on the Consumer Reports Best Buy Drugs website is accurate and describes generally accepted clinical practices. If we find, or are alerted to, an error, we will correct this as quickly as possible. However, Consumer Reports and its authors, editors, publishers, licensors and any suppliers cannot be responsible for medical errors or omissions, or any consequences from the use of the information on this site. Please refer to our user agreement at for further information. Consumer Reports Best Buy Drugs should not be viewed as a substitute for a consultation with a medical or health professional. This report and the information on are provided to enhance your communication with your doctor, rather than to replace it. 13 Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs

14 Sharing this Report This copyrighted report can be freely downloaded, reprinted and disseminated for individual noncommercial use without permission from Consumers Union or Consumer Reports magazine as long as it clearly attributed to Consumer Reports Best Buy Drugs. We encourage its wide dissemination as well, for the purpose of informing consumers. However, Consumers Union does not authorize the use of its name or materials for commercial, marketing or promotional purposes. Any organization interested in broader distribution of this report should contact Wendy Wintman at Consumer Reports Best Buy Drugs is a trademarked property of Consumers Union. All quotes from the material should site Consumer Reports Best Buy Drugs as the source. Consumers Union 2004 References 1. Topol EJ, Falk GW. A coxib a day won't keep the doctor away. Lancet 2004; 364: Topol, EJ. Failing the public health refecoxib, Merck, and the FDA. New England Journal of Medicine 2004; 351 (17): Dubois RW, Melmed GY, Henning JM, Laine L. Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cox-2 inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy. Alimentary Pharmacologic Therapy 2004; 19 (2) Bombardier C. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. New England Journal of Medicine 2000;343: Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. New England Journal of Medicine 2002; 347(26): Farkouh ME, Kirshner H, Harrington RA, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004;364(9435): FitzGerald GA, COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat. Rev. Drug Discov. 2003;2: Fitzgerald GA. Coxibs and cardiovascular disease. New England Journal of Medicine 2004;351(17): Food and Drug Administration. Medical Officer review, 1999: Vioxx. NDA (accessed Nov.12, 2004). 10. Garcia Rodriguez LA, Varas-Lorenzo C, Maguire A, et al. Non-steroidal antiinflammatory drugs and the risk of myocardial infarction in the general population. Circulation 2004;109(24): Gøtzsche PC. Reporting of outcomes in arthritis trials measured on ordinal and interval scales is inadequate in relation to meta-analysis. Ann. Rheum. Disease 2001;60: Krum H, Liew D, Aw J, Haas S. Cardiovascular effects of selective cyclooxygenase-2 inhibitors. Expert Review of Cardiovascular Therapy 2004;2(2): Moore R. Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs. British Medical Journal1998;316: Mukherjee D. Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events. Biochemical Pharmacolog. 2002;63(5): Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. Cox-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002;360(9339): Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR. Non-steroidal antiinflammatory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet 2002;359(9301): Schnitzer T, Update of ACR guidelines for osteoarthritis: role of the coxibs. J. Pain Symptom Management 2002;23(4 Suppl):S24-30; discussion S Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs non-steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. Journal of the American Medical Association 2000;284(10): Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004;109(17): Strand V, Hochberg MC. The risk of cardiovascular thrombotic events with selective cyclooxygenase-2 inhibtors. Arthritis Rheum 2002;47: Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomized controlled trials. Ann Rheum Disease 2004;63(8): Hopper L, Brown TJ, Elliot RA et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: a review. British Medical Journal Online 2004 (October 8); Bjordal JM, Ljunggren AE, Klovning A, Slordal L. Non-steroidal anti-inflammatory drugs, including cox-2 inhibitors, in osteoarthritic knee pain; meta-analysis of randomized placebo controlled trials. British Medical Journal Online 2004 (November 23); Consumer Reports Best Buy Drugs Non-Steroidal Anti-Inflammatory Drugs