Study: Most Painkillers Up Heart Attack Risk

But Researchers Say Risk Is Minimal for Low Doses of Painkillers

From the WebMD Archives

June 15, 2005 -- A new study shows that most prescription and over-the-counter painkillers increase the risk of heart attacks.

In the wake of the largest study to date showing most nonsteroidal anti-inflammatory drugs (NSAIDs) -- including ibuprofen, naproxen, and Celebrex -- increase the risk of heart attacks in people with arthritis, experts are once again urging all involved to weigh their individual risks when choosing a painkiller.

"This is a class effect of all the drugs," researcher Gurkirpal Singh, MD, professor of medicine, immunology, and rheumatology at Stanford University Medical School in Palo Alto, Calif., tells WebMD. Singh's study was presented at the Annual European Congress of Rheumatology in Vienna, Austria.

But the study shows the risk is minimal at lower doses.

This controversy over painkillers and heart attacks first focused on drugs like Vioxx, Bextra, and Celebrex -- so called Cox-2 drugs. But Singh points out that even traditional anti-inflammatory painkillers carry this heart risk.

"All the hysteria was over the Cox-2 drugs, and we are saying that it's not just Cox-2 ... drugs that are doing it. It could occur with any NSAID." He says that some of the older, traditional NSAIDs are associated with the highest heart risk.

New Warnings

Last April, the FDA issued new label warnings for all anti-inflammatory painkillers -- prescription and over the counter.

Prescription painkillers will now carry "black box" alerts warning of heart disease and stroke risk. Over-the-counter brands -- usually taken at lower doses and for a shorter amount of time -- must alter their labels to include more risk information. At the same time, the FDA stressed that there was no increased risk from short-term use of over-the-counter painkillers. They recommend checking with your doctor if you need over-the-counter painkillers for more than 10 days.

Aspirin is not included in the warnings as there is strong evidence that it can help prevent heart disease. Acetaminophen (Tylenol) is not an anti-inflammatory drug and also is not included in the warnings.

Drugs With the Highest Risk

Indomethacin (Indocin) and sulindac (Clinoril) -- both traditional NSAIDs -- had the highest risk in the new study. Indomethacin increased heart risk by 71% and sulindac by 41%.

Mobic upped risk of heart attack by 37%, while the recently pulled Cox-2 drug Vioxx increased risk by 32%, the study showed. Ibuprofen (Advil, Motrin) increased risk by 11%. Celebrex -- the sole Cox-2 drug still on the market in the U.S. -- increased risk of heart attack by 9%. The study did point out one NSAID, Relafen, that was not associated with an increased risk of heart attacks.

In a study released last week in the British Medical Journal, ibuprofen was associated with a 24% higher risk of heart attack.ibuprofen was associated with a 24% higher risk of heart attack.

In the new study, people who took Bextra had no increased risk of heart attack. Bextra was recently removedBextra was recently removed from the market during the FDA's sweeping review of anti-inflammatory drugs.

"From what I understand, this drug was pulled mainly due to skin reactions rather than [heart] risk," Singh says. Bextra has been associated with a potentially fatal skin disease called Stevens-Johnson syndrome.

Risk increased with escalating doses of all the NSAIDs. The higher the dose, the greater the risk, the study showed.

Little Risk With Lower Doses

Little to no risk was seen with lower doses of NSAIDs.

  • There was a 2% risk of heart attack with 150 milligrams a day or less of diclofenac (Arthrotec, Cataflam, Voltaren). That rose to a 37% increase in heart attack risk with doses over 150 milligrams a day.
  • A 7% increase in heart attacks with 1,000 milligrams a day or less of naproxen (Aleve, Anaprox, Naprosyn) rose slightly to a 16% risk with more than 1,000 milligrams a day.
  • Celebrex was associated with a 1% increase with 200 milligrams a day or less but a 24% increase with higher doses.

As a whole, all traditional NSAIDs slightly raised the risk of heart attack by about 12%. Compared with traditional NSAIDs, the only Cox-2 drug to raise heart risk was Vioxx. The new findings are based on data from Medi-Cal, California's Medicaid program, and included all adult arthritis patients treated with an NSAID between 1999 and 2004. Of this population, more than 15,000 had a heart attack.

Don't Live in Pain or Fear

So what's a person to do?

"I don't think they should live in pain or live in fear," Singh says. "Increase in the risk of heart attack is a common phenomenon with a large number of NSAIDs and the choice should be made in consultation with a physician."

Singh says these drugs have similar effectiveness and the choice on which painkiller to use should depend on heart and bleeding risks. Another potentially serious side effect of NSAIDs is bleeding stomach ulcers.

Clearly drugs that have high increased risk of heart attack should not be prescribed to patients with risk factors for heart disease, he says.

Painkillers and Stomach Bleeding

On the flip side, drugs that have better stomach safety should be prescribed in patients who have a high risk of stomach bleeding, he says. Cox-2 drugs were originally developed to reduce the risk of stomach bleeding associated with traditional NSAIDs.

"People should discuss alternative treatments with their doctor," Singh says. "For some people, Tylenol (acetaminophen) may be enough, but if they do need an NSAID, they need to determine if it is worth taking the small increase in risk."

Compared with smoking, NSAID use poses a very low risk of heart attack, he points out.

"If a person is at low risk for [heart attacks], this increase can be ignored," says Chris J. Hawkey, MD, co-director of the Institute for Clinical Research and head of the Wolfson Digestive Diseases Center at University Hospital in Nottingham, England.

Hawkey says patients at high risk of stomach bleeding who need an NSAID should ask their doctor about taking a strong acid blocker with their painkiller. These drugs, including Aciphex, Prevacid, Prilosec, and Nexium, help decrease the risk of further stomach problems.

Singh is looking at whether the use of aspirin will cut heart risks seen with these drugs. Aspirin, a blood thinner, is known to decrease risk of heart attack and stroke. "If you take aspirin with these drugs, will that make a difference?" he asks.

In the recent British Medical Journal study, aspirin did not affect the risk of heart disease.aspirin did not affect the risk of heart disease.

Patients on NSAIDs, particularly those with known heart disease risk factors, should do what they can to lower the risk of heart attacks. This includes stopping smoking and keeping blood pressure under control, Hawkey says.

WebMD Health News


SOURCES: Annual European Congress of Rheumatology of EULAR, Vienna, Austria, June 8-11, 2005. Gurkirpal Singh, MD, professor of medicine, immunology, and rheumatology, Stanford University Medical School, Palo Alto, Calif. Chris J. Hawkey, MD, co-director, Institute of Clinical Research; Wolfson Digestive Disease Center, Institute of Clinical Research, University Hospital, Nottingham, England.

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