NSAIDs and the Risk of Heart Problems and Stroke

Most nonsteroidal anti-inflammatory drugs increase risk of cardiovascular events and stroke.


Nonsteroidal anti-inflammatory drugs (NSAIDs) ­– traditional ones such as ibuprofen (Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), and the COX-2 selective inhibitor celecoxib (Celebrex) – are widely used to treat arthritis because they help relieve pain and reduce inflammation. But evidence has emerged in recent years indicating these pain relievers also increase the risk of heart attacks, strokes and other heart problems.

All NSAIDs work by blocking hormone-like substances called prostaglandins, which are involved in pain and inflammation as well as many other bodily functions, including protecting the stomach lining from its own digestive fluids. Traditional NSAIDs block prostaglandins by inhibiting two enzymes – so-called COX-1, which plays a role in stomach protection, and COX-2, which is responsible for pain and inflammation. The newer celecoxib blocks only the COX-2 enzyme; for that reason it is less likely to cause damage to the stomach.

Since 2001, several studies – including one from 2011 in BMJ and a 2013 review in The Lancet – have linked long-term, high-dose NSAID use to a greater risk for heart attack, stroke, heart failure and death from cardiovascular disease. Another COX-2 selective inhibitor, the very popular Vioxx (rofecoxib), was pulled from the market in 2004 over concerns about an increased risk of heart attacks and stroke.

Should these risks stop you from taking an NSAID for arthritis pain?

That depends on how often you take them, says Steven B. Abramson, MD, chair of the Department of Medicine at NYU Langone Medical Center. “If you’re just taking them intermittently, they’re probably very safe,” he says. But if you plan to take these drugs daily, he suggests that you weigh the risks against your need for arthritis pain relief. That need may be significant, considering arthritis pain itself can be disabling.

When deciding whether to take an NSAID, also consider your existing heart risks. People with chronic conditions such as rheumatoid arthritis, obesity or diabetes already face higher odds of developing heart problems, as do those with existing risk factors (such as high blood pressure and high cholesterol) and a strong family history of heart disease. NSAIDs add yet another risk factor into the mix.

Watch the Drug – and the Dose

Which NSAID you choose may make a difference. Studies suggest that naproxen (Aleve) is less likely than the other NSAIDs to harm the heart. “If I have to put somebody on chronic NSAIDs, naproxen might be my first choice,” Dr. Abramson says. Yet naproxen might not be the best choice for someone with ulcers, because it’s been linked to GI bleeding and ulcers more than some of the other NSAIDs.

The dose you take also matters. “The notion that naproxen seems to be safer is based on studies of a full dose – 500 mg twice a day,” Dr. Abramson says. At this dose, the drug seems to stop platelets from clumping together and forming clots – similar to aspirin’s effect. This could explain why it poses less of a heart risk. “If you’re taking lower doses, there’s no evidence that it’s safer than the other NSAIDs.”

With other NSAIDs, a lower dose might be more protective. “Celecoxib appears to be relatively safe in patients if used at the 100 mg dose,” Dr. Abramson says.

Take Care with NSAIDs

“My take is that patients who need to take NSAIDs should do so with appropriate cautions,” says Daniel Furst, MD, a rheumatologist at UCLA Medical Center.

If you’re at high risk for heart disease due to high blood pressure or high cholesterol and your doctor thinks you need NSAIDs, it’s important to control your existing risks, Dr. Abramson advises. Diet, exercise, and weight loss can both protect your heart and take weight off your joints, improving your arthritis. You may also need medication to bring down stubbornly high blood pressure and cholesterol.

Consider your medical history before deciding to take one of these drugs, especially if you have family members with heart disease or you’ve had a past heart attack. “As always, one needs to consider the whole story and the whole patient, not just the literature data,” says Dr. Furst.