Fda Strengthens Warning That Nsaids Increase Heart Attack And Stroke Risk
- By Gregory Curfman, MD, Assistant Professor of Medicine, Former Editor-in-Chief, Harvard Health Publishing
Back in 2005, the FDA warned that taking nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen increased the risk of having a heart attack or stroke. In July 2015the FDA took the unusual step of further strengthening this warning. This was done on the advice of an expert panel that reviewed additional information about NSAIDs and their risks. Because ibuprofen and naproxen are available over-the-counter and so widely used, its important to be aware of the ibuprofen warnings and naproxen warnings and to take steps to limit the risk.
Many people take NSAIDs to relieve mild to moderate pain. These medications may be particularly effective in conditions in which pain results primarily from inflammation, such as arthritis or athletic injury. While you can buy ibuprofen and naproxen on your own, doctors commonly write prescriptions for celecoxib , diclofenac and other NSAIDs. Aspirin is also an NSAID, but it does not pose a risk of heart attack or stroke. In fact, aspirin is commonly used to prevent heart attacks and strokes. So, it is not covered by this warning.
The FDA has noted the following ibuprofen warnings and naproxen warnings along with similar risks of other NSAIDs:
The Results Of The European Study
The actual study featured in the various media outlets has been carried out by European researchers led by the University of Milan and involved over 7 million total patients. The nested case-control study funded by the European Union examined data coming from five healthcare databases coming from the United Kingdom, Italy, the Netherlands, and Germany. Researched investigated the cardiovascular safety of several NSAIDs including, but not limited to, ibuprofen, as well as several others such as naproxen, nimesulide, and indomethacin. All patients included in the databases received at least one prescription NSAID drug over the course of ten years . Note that all these people did, in fact, receive these medications to treat long-term conditions such as arthritis or other forms of chronic pain. Scientists found that patients who had taken any anti-inflammatory medicine in the last 14 days had a 19 percent increased chance of being admitted to a hospital for heart failure symptoms compared to those who didnt.
How Nsaids Harm The Heart
NSAIDs pose a risk to the cardiovascular system for two main reasons. First, they change levels of substances in the blood that make clots more likely. A blood clot can block a narrowed artery in the heart, triggering a heart attack. Second, NSAIDs change blood flow in the kidneys, causing the body to retain more salt and water, explains Dr. Antman. That causes blood pressure to rise, which also boosts the risk of a stroke. High blood pressure also makes people more prone to atrial fibrillationa rapid, quivering motion of the heart’s upper chambers.
In fact, a recent study found a higher risk of atrial fibrillation in people who had taken NSAIDs during the past 15 to 30 days compared with people who had never taken NSAIDs.
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Nsaid Pain Relievers Such As Naproxen And Ibuprofen
If you have atrial fibrillation and are on blood thinners to lower your risk of blood clots and stroke, beware of nonsteroidal anti-inflammatory drugs . NSAIDs include common pain relievers naproxen and ibuprofen .
These drugs, which are available over the counter and are used commonly to relieve the aches and pains that all of us have, are also blood thinners, says Dr. Ellis. If you combine them with prescription blood thinners, you could have serious bleeding.
When To Seek Medical Attention
If you are taking NSAIDs and feel any new signs or symptoms such as fatigue, dizziness, headache, shortness of breath, or belly, chest, or back pain, you may be experiencing a medical complication from your NSAID use. You should seek immediate medical attention, even if you do not feel that your symptoms are life-threatening.
If you experience any of the following symptoms, whether you have been taking NSAIDs or not, you could be having a heart attack or stroke. Call an ambulance or have someone take you to the emergency room immediately if you experience:
- New or worsening chest pain
- Have chest discomfort that feels like someone is sitting on your chest
- Sudden slurred speech
- Weakness in one part or side of the body
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Risk Of Heart Failure
Non-steroidal anti-inflammatory drugs are associated with elevating blood pressure as well as sodium and fluid retention. Both of these effects may unmask previously undiagnosed heart failure, or worsen the symptoms in people known to already have heart failure.
Research published in the British Medical Journal in September 2016 studied 92,163 people admitted to hospital with heart failure, and found NSAID use in the two weeks prior to admission was associated with a 19% increased risk of hospital admission for heart failure. This was compared with people who had not used NSAIDs prior to admission.
The association of NSAIDs with an exacerbation of heart failure was also seen in many older studies. For example, an Australian study in 2000, suggested almost 20% of all heart failure related admissions to hospital may be attributed to recent NSAID use.
Strengths And Limitations Of Study
Our findings, which focused only on prescription NSAIDs, might apply to NSAIDs obtained over the counter as well. Although over-the-counter NSAIDs are probably typically used at lower doses, by younger people, and for shorter durations than prescribed NSAIDs, they are sometimes available at the same doses than those prescribed36and may be inappropriately overused.37 Therefore, our findings could have large scale consequences in public health and further research needs to assess the safety of over-the-counter NSAIDs under the conditions they are typically used.
The present study, conducted as part of the EU funded SOS Project, is based on data from large and unselected populations and obtained by combining different healthcare databases together. The same approach was considered in several other EU funded projects addressing various issues on drug safety, such as the arrhythmogenic risk of drugs , safety of vaccines , and detection of adverse drug reactions .1819 The use of five different data sources from the SOS Project should be considered a strength of this study because it allowed us to compare the risk of heart failure associated with many individual NSAIDs as used in different populations and healthcare systems from four EU countries.
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Heart Attack Risk With Painkillers Starts Within A Week: Study
Common painkillers such as ibuprofen and naproxen are already known to raise peoples risk of a heart attack. Now a new study shows the risk comes within the first week of using the drugs.
The study doesnt mean that everyone should avoid taking the pills to treat headaches, lower fevers and reduce aches and pains, but does suggest people who know they have a bigger-than-average heart attack risk should avoid long-term use and high doses, the researchers said.
The study involves drugs called nonsteroidal anti-inflammatory drugs or NSAIDS for short. They include ibuprofen, sold under brand names like Advil or Motrin naproxen, like Aleve as well as prescription arthritis drugs known as COX-2 inhibitors, such as Celebrex.
Tylenol, known generically as acetaminophen, is not an NSAID. The researchers did not look at aspirin, another NSAID commonly prescribed to lower heart attack risk that works in a slightly different manner.
The study also looked at Vioxx, a prescription drug pulled from the market in 2004 after it was shown to raise the risk of strokes and heart attacks.
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Michèle Bally of McGill University and colleagues pooled all the studies they could find on NSAIDs and heart attacks. They settled on data covering 446,000 people using NSAIDs, including 385,000 who did not have heart attacks, known medically as myocardial infarctions.
This was observed for all traditional NSAIDs, including naproxen, they added.
Nsaids And Blood Pressure
The new findings don’t surprise heart experts, says Andrew L. Smith, medical director for the heart failure and transplant programs at Emory University in Atlanta.
“The data from this study is not surprising to those of us who manage a lot of patients with heart failure,” Smith tells WebMD. “NSAIDs can contribute to high blood pressure. This is not commonly recognized among primary care providers. It is a difficult situation, because a lot of heart patients have arthritis and other problems for which these medicines provide relief.”
With all the attention given the heart risks of Vioxx, it’s easy to forget that over-the-counter painkillers also have risks, says Carl Lavie, MD, medical co-director of cardiac rehabilitation and preventive cardiology, Ochsner Clinic Foundation in New Orleans.
“Doctors don’t think anything of giving patients these NSAIDs that raise blood pressure, inhibit the aspirin they need for heart disease prevention, and increase the risk of heat attacks and strokes,” Lavie tells WebMD. “And now this paper, like others before it, shows higher heart failure risk. Doctors have to recognize that all these drugs have risks — not just the ones advertised by the lawyers.”
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Nsaid Use And Heart Failure Risk
A total of 16081 cases and 1193537 matched controls were current users of NSAIDs. Figure 1 reports the distribution of current use of individual NSAIDs among all cases and controls. Among controls, the most frequently used traditional NSAIDs were diclofenac , nimesulide , and ibuprofen , while the most frequently used COX 2 inhibitors were celecoxib , rofecoxib , and etoricoxib .
Fig 1 Distribution of current use of individual NSAIDs among cases and controls and pooled associations between current use of individual NSAIDs and risk of hospital admission for heart failure, with past use of any NSAID as reference. Estimates obtained by pooling individual data from all available databases. Pooled odds ratios and 95% confidence intervals estimated by fitting a conditional logistic regression model after correcting for available covariates
The Lowest Dose For The Shortest Time
NSAID options similar to aspirin include salsalate or choline magnesium trisalicylate . They’re easier on the stomach than aspirin. But they don’t quell inflammation as well, and their cardiovascular effects haven’t been well studied.
Unfortunately, some people take painkillers every day because they want to prevent discomfort. “That’s a problem because it turns occasional use into chronic use,” says Dr. Antman. No matter what you take, he advises, “use the safest drug at the lowest dose for the shortest period of time to control your symptoms.”
Image: Inna Luzan/Getty Images
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Painkillers Worsen Heart Failure
May 22, 2006 — Common painkillers raise the risk of heart failure-related hospitalization in people over 60, a new study shows.
The risk is even greater for those who already have heart failure. And even very short-term painkiller use can be dangerous, the study finds — especially for people taking blood-pressure-lowering medications.
The drugs are known as nonsteroidal anti-inflammatory drugs or NSAIDs. Those implicated in the study are:
- Indocin tripled the risk of heart failure-related hospitalization.
- Naproxen doubled the risk of heart failure-related hospitalization.
- Ibuprofen increased the risk of heart failure-related hospitalization by 43%.
Who May Not Be Able To Take Ibuprofen
Do not take ibuprofen by mouth or apply it to your skin if you:
- have ever had an allergic reaction or symptoms like wheezing, runny nose or skin reactions after taking aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs such as naproxen
To make sure ibuprofen tablets, capsules, granules or liquid is safe for you, tell your doctor or pharmacist if you:
- have ever had bleeding in your stomach or a hole in your stomach caused by an NSAID
- have had a hole in your stomach, bleeding in your stomach or a stomach ulcer more than once
- have a health problem that means you have an increased chance of bleeding
- have severe heart failure, severe kidney failure or severe liver failure
- are trying to get pregnant
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Pain Relief That’s Safe For Your Heart
Some common painkillers may boost the odds of a heart problem. Use them wisely to lessen your risk.
In 2004, the drug maker Merck pulled rofecoxib off the market, following revelations that the popular prescription painkiller increased the risk of heart attacks and strokes. That action triggered a closer look at drugs in the same class, known as nonsteroidal anti-inflammatory drugs . These drugs, which are widely used to ease pain, quell inflammation, and cool fevers, include over-the-counter drugs such as aspirin, ibuprofen , naproxen and the prescription drug celecoxib .
Soon, all NSAIDs except aspirin were suspected of increasing heart attack risk. That prompted the FDA to mandate a warning about this side effect on all NSAID labels. Earlier this year, the agency considered dialing back the caution on naproxen, based on an analysis that showed a lower risk from naproxen compared with other NSAIDs. But a panel of expert advisers voted against the label change, so the warning remains the same for all NSAIDs.
With the exception of aspirin, all NSAIDs may boost the risk of having a heart attack.
Ibuprofen Or Naproxen Vs Prexige
The study by Farkouh and colleagues enrolled 18,325 arthritis patients. Nearly 17% of these patients were at high risk of heart attack and stroke.
The trial compared ibuprofen or naproxen to a new pain drug sold as Prexige in the U.K. and Canada.
Prexige is a member of the stomach-friendly family of pain drugs called Cox-2 inhibitors. Celebrex is the only member of this drug class sold in the U.S. Another Cox-2 drug, Vioxx, was taken off the market after people taking the drug had a suspiciously high number of heart attacks.
All of the high-heart-risk patients in the Farkouh study should have been taking low-dose aspirin. Sixty percent of them did. These patients should have had fewer heart attacks, strokes, and heart deaths than those who did not take aspirin.
But if the patients took aspirin and also took high-dose ibuprofen, they were nine times more likely to have a heart attack than were patients who took aspirin and Prexige. Patients who took ibuprofen without taking aspirin were no more likely to have a heart attack than those who took Prexige.
Farkouh and Nissen say there is strong evidence that ibuprofen blocks the blood-clot-preventing effects of aspirin. Both agree that the drugs do not interact if a person takes aspirin two hours before taking ibuprofen. But Farkouh says this approach will not work in the real world.
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Researchers Discover New Side Effects Of Non
According to a study presented at ESC Congress 2022, short-term use of non-steroidal anti-inflammatory drugs is linked to a first-time hospitalization for heart failure in individuals with type 2 diabetes.
NSAIDs are the most common form of anti-inflammatory medication. The most popular NSAIDs include aspirin, ibuprofen , and naproxen . However, despite their widespread use, these drugs can have side effects.
In our study, approximately one in six patients with type 2 diabetes claimed at least one NSAID prescription within one year, said first author Dr. Anders Holt of Copenhagen University Hospital, Denmark. In general, we always recommend that patients consult their doctor before starting a new medication, and with results from this study, we hope to help doctors mitigate risk if prescribing NSAIDs.
In the general population, NSAID usage has been linked to an increased risk of heart failure, however, data are lacking for patients with type 2 diabetes. NSAIDs may be significantly more harmful in people with type 2 diabetes since they are more likely to experience heart failure than those without the condition.
Prior to the first heart failure hospitalization, information on prescriptions for oral NSAIDs was gathered. The links between short-term NSAID usage and the likelihood of first-time heart failure hospitalization were analyzed using a case-crossover approach in which each patient served as his or her own control.
Meeting: ESC Congress 2022
The Cyclooxygenase Enzyme And Its Physiologic Roles
NSAIDs are cyclooxygenase inhibitors. COX is an enzyme, which produces prostaglandin H2 from arachidonic acid. PGH-2 is a metabolite converted into prostanoids by tissue specific enzymes.
Two basic isoforms of cyclooxygenase are known to date: COX-1 and COX-2. Initially, COX-1 was thought to be the constitutive form of the enzyme playing an important role in physiologic functions of the human body. At the same time, COX-2 was considered strictly inducible and thought to be responsible for inflammation and pain under pathologic circumstances. Recently, this theory was proven to be too simplistic. It is now known that COX-2 is permanently present in several tissues of the human body and plays an important role in multiple physiologic processes.
With regards to the most common serious ADRs of NSAIDs, it is important to understand the role of COX-1 in the formation of protective prostaglandin E2 and prostacyclin . Both of these play a protective role in the gastric mucosa. In thrombocytes, COX-1 forms thromboxane A2 , which is a prostanoid antagonizing the anti-thrombotic and vasodilating effect of PGI-2 formed in the arteries by both COX isoforms. Within the kidney, PGE-2 formed by COX-1 plays a decisive role in the regulation of glomerular filtration, while PGI-2 produced by COX-2 affects renin secretion. Finally, products of both COX isoforms play a role in the kidney regulating excretion of sodium and water.
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What Is The Link Between Nsaids And Heart Failure
If you have a history of cardiovascular disease or a weakened left side of your heart called left ventricular dysfunction, taking NSAIDs may worsen your heart failure.
This is because NSAIDs impair renal function by inhibiting the production of prostaglandin. As a result, water and sodium are retained and blood flow to the kidneys is reduced .
NSAIDs worsen kidney function, which throws off the homeostasis of the cardiovascular system. Retained fluid can overwhelm the weakened heart, a phenomenon called cardiac decompensation. Cardiac decompensation compromises the heart’s ability to pump blood while also worsening kidney function due to poor blood flow.