The Risk in Relief

Government recalls of popular pain medications due to heart-related risks have left many people searching for pain relief options.

by Jon Nalick

If reading recent studies linking several popular pain medications to increased heart attack risk is giving you a headache, a USC pharmacological scientist offers exactly two words of advice: Take aspirin.

James Adams, Ph.D., associate professor of molecular pharmacology and toxicology at the USC School of Pharmacy, says aspirin may not have the flash and allure of new drugs with massive advertising campaigns, but it remains an effective pain reliever.

With more than 100 years on pharmacy shelves, aspirin has been proven safe for long-term use—a major advantage at a time when the safety of high-profile drugs such as Celebrex, Bextra, Aleve and Vioxx has been called into question.

“For treating mild to moderate pain for long periods of time, the bottom line is: Do not take anything but aspirin. It has a long history, it is safe and it is the only non-steroidal anti-inflammatory drug [NSAID] shown to protect against stroke and heart attack,” Adams says.

A spate of clinical studies recently showed a link between the long-term use of Celebrex and Bextra and a higher-than-normal heart attack and stroke risk. Adams says that the findings were unsurprising because the drugs are members of a class of medications known as selective COX-2 inhibiting NSAIDs, which encourage blood coagulation.

“The COX-2 inhibitors cause blood clots and those can lead to heart attacks, strokes and kidney damage,” Adams says.

Although the exact mechanism remains unknown, COX-2 inhibiting NSAIDs appear to cause the formation of compounds in the blood known as thromboxanes, many of which trigger clotting.

For Vioxx, the risk was so pronounced—Adams says that as many as 100,000 people reported significant side effects—that its manufacturer, Merck, pulled it from the shelves in September 2004. In April 2005, responding to a request from the federal Food and Drug Administration (FDA), Pfizer pulled its drug, Bextra, from the shelves as well. At this time, Celebrex remains on the market because the FDA has concluded that its benefits outweigh its potential risks. Naproxen, the nonprescription active ingredient in Aleve, remains on the market for the same reason. FDA advisory panelists pointed out that although naproxen is associated with some risk of heart attack, it may be significantly less than the risk associated with selective COX-2 inhibitors. The panel called for additional study on the drug.

Still, the FDA began requiring stronger warning labels for all NSAIDs to explain the risks and issuing stronger reminders about limiting the dose and duration of treatment.

“The really sad thing is that the FDA knew from the clinical trial data that chest pain [possibly resulting from blocked arteries] was a demonstrated risk with long-term use, but they approved Vioxx anyway,” Adams says.

The reason the FDA gave their approval, he adds, was that the drugs were never intended for long-term use and the instructions recommend usage limited to a maximum of two weeks.

The problem was that many NSAID users frequently disregarded the instructions and began using the drugs essentially indefinitely, unaware of the potential risks.

Some people may want to steer clear of COX-2 inhibiting NSAIDs altogether. Among them are people with a history of heart attack, stroke and congestive heart failure, a condition in which the heart fails to pump enough blood to meet the body’s needs.

A recent study found that NSAID use was a major factor in 20 percent of first hospital admissions for congestive heart failure. It suggested that NSAIDs decrease the ability of the body to excrete excess salt and water, resulting in fluid retention and the beginning of heart failure. Patients with a history of heart disease who used naproxen, piroxicam or tenoxicam were 24 times more likely to develop congestive heart failure than were heart patients who had not used any NSAIDs.

With FDA warnings and new studies appearing regularly in the press, Adams says it is not surprising that NSAID use has plunged—a development he sees as good news.

“Non-steroidal anti-inflammatory drugs are perfectly safe to use for convalescing from an injury like a twisted knee, but people with long-term pain need to switch to something else,” he says.

He notes that alternatives such as topical creams containing capsaicin can bring temporary relief to minor muscle strains and joint pain. For major joint pain or pain caused by injury, he says, ice brings immediate pain relief and is fairly long lasting.

Adams says that acetaminophen, the active ingredient in Tylenol, is an effective pain reliever, but can cause liver and kidney damage. In addition, it short-circuits the body’s ability to sense pain without addressing the underlying cause of the inflammation responsible for it.

“You need to be careful. For long-term use of acetaminophen, you really need to be under the care of a doctor who can carefully explain these issues,” he says.

Adams says that goes for any drug, including aspirin, which can interact with blood-thinning agents to cause excessive bleeding and can also cause ringing in the ears in some people.

Even with short-term use, aspirin can irritate the stomach. To avoid this, Adams notes, it should be taken after eating or with an eight-ounce glass of water. Alternatively, aspirin can be taken with antacids or proton-pump inhibitors, both of which suppress the production of acid that causes stomach upset.

“People need to realize that pain relievers are serious medicine and directions need to be followed,” he says, adding that the physicians who prescribe them so readily share equal blame.

“Doctors often just want patients to take a drug and go away—and patients also want to just take a drug and go away. But unfortunately, many patients will continue to use the drugs without going back to the doctor, or add over-the-counter drugs to self-treat their pain and end up causing more problems than are solved in the long run,” he says.

Adams emphasizes that the most important thing is for patients to discuss all medications they take—both over-the-counter and prescription—with their doctor or pharmacist, especially when taking them for extended periods of time.

He adds, “Probably the first thing the physician should ask a patient is, ‘Which medications are you taking right now?’ And if the doctor doesn’t ask, then the patient should say, ‘Here are the drugs I am taking. Which ones should I not take anymore?’ This important communication can help take the risk out of pain relief.”