What antiinflammatory has the least side effects?

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What's the risk of NSAIDs?
NSAID heart attack risks
What about chronic pain?
What about low-dose aspirin?
How much should you worry about the heart risk of NSAIDs?
Disclaimer:
Gastrointestinal symptoms
Heart problems
How should you think about taking NSAIDs in view of the possible side effects?
What about using NSAIDs during pregnancy?
What is the proper dosing for NSAIDs?
Can I combine NSAIDs with other drugs?
When should I stop the drug and get immediate medical attention?
When should I call my doctor about changing NSAID dosage or medications?
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Heart Health

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used pain relievers. These include ibuprofen (Advil, Motrin) and naproxen (Aleve) and prescription-only NSAIDs. In addition to concerns about stomach ulcers and kidney damage, regular use raises heart risks.

What's the risk of NSAIDs?

The link between NSAIDs and heart problems is well established.

All non-aspirin NSAIDs appear to be associated with higher risk of heart problems. The risk is greatest in those with known heart disease or multiple risk factors for it.
It's not known for sure yet which, if any, of the various NSAIDs in use are more risky than others. However, in some studies naproxen has shown the smallest risk.
The higher the NSAID dose you take, and the longer you take it, the greater the potential risk.

Use only what you need. Don't start off by "bombing" pain with NSAIDs. Take the lowest dose first, and then raise it only if it doesn't work. Many people obtain acceptable relief of their symptoms, such as pain and swelling, at low to moderate doses.
Stop as soon as you can. Severe pain demands a response, but when it becomes a dull ache, try to ease off the NSAIDs and shift to comforting remedies like hot baths or cold packs.

NSAID heart attack risks

Some studies have shown that people who take NSAIDs also have more heart attacks. The reason why is not fully understood, but the evidence is consistent enough to warrant extra caution. That is especially true for people with an above-average chance of heart problems because of older age, overweight, smoking, high cholesterol or blood pressure, or a previous heart attack or stroke.

If you are at above-average risk of heart problems and use NSAIDs, how much does your risk go up? An analysis comparing prior research of diclofenac, celecoxib or ibuprofen estimated that 7 to 8 extra cardiovascular events (such as heart attack) would occur each year among 1000 people taking these drugs; for those taking naproxen, no increased risk was observed. This is considered a small added risk. If an NSAID is your only option to provide enough pain relief, you and your doctor may decide this added risk may be worth taking.

What about chronic pain?

People with chronic muscle or joint pain—pain that lasts for several months or more—are in a different situation when it comes to NSAIDs. They may require daily doses of medication just to function or get a good night's sleep. What should they do?

NSAIDs are not the only way to control muscle and joint pain. By deploying a range of remedies, you may be able to reduce your need for NSAIDs or even eliminate it. These add-ons to pain relievers include heat or cold, physical therapy, exercise, and weight loss—especially if the problem is arthritis. (See "NSAID alternatives for arthritis.")

What about low-dose aspirin?

Aspirin is an NSAID, too. It increases the risk of bleeding, but when used appropriately, it has a net benefit for heart health for those at high risk of future heart problems because it prevents the clotting that leads to heart attacks and strokes. However, some studies suggest that other NSAIDs may interfere with aspirin's ability to prevent clots and the heart attacks they cause. If you take low-dose aspirin and another NSAID, be sure to take the aspirin at least 60 minutes before the pain relieving NSAID.

How much should you worry about the heart risk of NSAIDs?

NSAIDs present a small additional heart risk, but keep it in perspective. There are even more important risks that you might need to address, including smoking, being overweight, eating an unhealthy diet, and not exercising enough. There are a lot of things that cause heart disease that people need to worry about more than NSAIDs.

If you want or need to rely less on NSAIDs, discuss the following options with your doctor. Choices need to be tailored to your unique needs and health risk profile.

Topical therapies. Diclofenac (Voltaren) gel applied to the skin can provide relief. Not enough is absorbed into your body to increase heart risks. Also you can try topical lidocaine.
Acetaminophen. For pain relief, try acetaminophen (Tylenol, other brands) first. Understand that acetaminophen does not target inflammation, so if your arthritis pain comes with swelling, acetaminophen may not serve your needs completely. Taking too much can damage the liver, so take only what your doctor says is safe.
Safer NSAIDs? The final word is not in yet on which NSAIDs are the most risky for the heart. Naproxen (Aleve, Naprosyn, Anaprox) may be less likely to cause heart problems compared to other non-aspirin NSAIDs.
Soothe without pills. In old Hollywood movies, soldiers just clenched their teeth on a bullet when painkillers were not available, but you can do better. Exercise, weight loss, physical therapy, joint-supporting splints, massage, and acupuncture are all possible ways to reduce pain and reliance on pain relievers.

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No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

Gastrointestinal symptoms

Gastrointestinal symptoms are the most common side effects of NSAIDs. They are most likely to be stomach irritation and the sensations known as "heart burn" (which has nothing to do with your heart). In severe cases, NSAIDs can irritate the lining of your stomach so that an ulcer (a small erosion) forms. In the worst cases, such an erosion can lead to internal bleeding, which may be life-threatening. Perforation, meaning a “hole” in the stomach, can also occur in rare cases. This is an urgent problem requiring prompt medical attention.
Stop the drug and call your physician immediately if you have any severe abdominal pain or a black, tarry stool (bowel movement) or any blood in your stool.
To help reduce irritation of the stomach and prevent an ulcer,
- Take NSAIDs at the end of a full meal or with an antacid
- Limit alcohol intake (since alcohol can also irritate your stomach)
If you develop gastrointestinal problems, your physician may switch you to another drug (such as a COX-2 selective inhibitor – see the below section on this type of agent) or may add a drug to help reduce stomach irritation.
Drugs that reduce stomach irritation include misoprostol (Cytotec), or a proton pump inhibitor such as omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), or rabeprazole (Aciphex). These drugs can considerably reduce your risk of an ulcer and internal bleeding.

The black box warning for NSAIDs related to gastrointestinal risk reads as follows, in an example from the labeling for the NSAID naproxen (Naprosyn®):

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Heart problems

The FDA has required a block box warning about cardiovascular thrombotic events be placed in the package description of all NSAIDs other than aspirin, including COX-2 specific and selective agent, and patients at high risk for cardiovascular disease need to weigh the risks and benefits with their physician before taking any NSAID or (COX-2 specific or selective agent). The black box warning for NSAIDs related to cardiovascular risk reads as follows, in an example from the labeling for the NSAID naproxen (Naprosyn®):

"Cardiovascular risk: Serious cardiovascular thrombotic events: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use."

How should you think about taking NSAIDs in view of the possible side effects?

Years ago, doctors thought of NSAIDs as being very safe. They still are acceptably safe for many people, but longer-term experience and medical studies have shown that there are definite risks. Think about these things before you start NSAIDs and consider them again if you are taking them for a while:

Do you have risk factors for the side-effects of these medications? For example, do you have a prior history of ulcer, a known bleeding problem? Are you are higher-than-average cardiac risk, such as if you have had a heart attack, have high blood pressure (especially if not well-controlled) or have diabetes. Older people have more GI and cardiovascular risk from NSAIDs.
Have you been told of abnormal kidney function? NSAIDs can negatively affect kidney function.
Will you be taking NSAIDs for a short or long time? Although heart issues have been described after short uses of NSAIDs, most of the time the problems come with prolonged use. There are situations where long-term use of NSAIDs is appropriate, but in many other situations the need for long-term NSAIDs calls for a discussion with your health care provider about possible alternatives.

What about using NSAIDs during pregnancy?

A good resource for the use of NSAIDs in pregnancy can be found at MotherToBaby's factsheet on naproxen. They point out that “It is unclear if naproxen use may affect the ability to become pregnant.” They note that “studies have suggested that the use of NSAIDs may increase the chance of miscarriage,” but suggest that this may be in the setting of long-term use of NSAIDs. Data to date overall do not suggest that NSAIDs cause any abnormalities of babies. NSAIDs are not recommended for use after week 20 of a pregnancy.

What is the proper dosing for NSAIDs?

When you are trying an NSAID for the first time, take the full dose prescribed every day, unless instructed otherwise. It may take as long as two weeks to build up to a "blood level" of the drug, and the drug may not help very much until then. If you take the drug irregularly, you may never know whether it actually can help you. This could lead to your being switched to a second drug when the first one actually could have helped. Each new drug you take carries a risk of allergic reaction (such as skin rash). Therefore, it's important to find out if a drug can help you before switching to another.

Do not exceed the dose of the drug prescribed. The extra benefit is usually small and the increased risk is significant.

If you are taking the medicine regularly and miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Do not take a double dose. If your arthritis improves, discuss with your physician the possibility of decreasing your dose of the NSAID.

Can I combine NSAIDs with other drugs?

Do not mix one NSAID with another. For example, don't take aspirin or ibuprofen with any other nonsteroidal anti-inflammatory drugs. However, your physician may wish you to combine low-dose aspirin with an NSAID for heart attack or stroke prevention. This is an individual decision for each patient, and you should discuss this with your physician, since combining an NSAID with aspirin can increase the risk of ulcer. Acetaminophen, especially in low dose, appears less likely to irritate the stomach than NSAIDs, so in many cases it is reasonable to take acetaminophen along with (or instead of) NSAIDs.

Always read the ingredients listed on the label of over-the-counter products. If acetylsalicylic acid or salicylate is listed, it may be better not to take this with NSAIDs, unless advised by your physician. Keep in mind that Alka-Seltzer, Anacin and some types of Excedrin contain aspirin.

If you are taking medications for high blood pressure, have your pressure checked regularly while on the nonsteroidal anti-inflammatory drug. This is especially important within the first several weeks of starting the drug. In some patients, NSAIDs can elevate the blood pressure.

When should I stop the drug and get immediate medical attention?

You should cease taking NSAIDs if:

Signs of allergy occur, such as rapid breathing, gasping, wheezing, hives, skin rashes, puffy eyelids, and/or rapid heart beat.
You develop:
- vision abnormalities.
- dizziness, depression or confusion.
- yellowing of the eyes that could indicate liver injury (although liver injury is rare and your liver function is checked when you have standard chemistry blood tests, which should be done periodically, when you are taking an NSAID).
Your urine becomes cloudy or bloody, the amount of urine you pass should suddenly decrease, or you develop new ankle swelling, all of which could indicate kidney problems. This is especially important to watch for if your kidney function has been noted, on lab testing, to have been abnormal in the past.

When should I call my doctor about changing NSAID dosage or medications?

Talk to your doctor about switching away from NSAIDs if:

You develop swelling of the ankles or sudden weight gain after starting one of these drugs due to fluid retention.
You develop decreased hearing or ringing in your ears.
You are pregnant or planning to become pregnant.

Updated: 12/10/2021