Use of NSAIDs Risky for Osteoarthritis Patients

By Pat Anson, PNN Editor

It’s long been known that nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen can raise the risk of cardiovascular problems. A large new study in Canada has documented how NSAIDs can significantly raise the risk of heart disease, congestive heart failure and stroke in people with osteoarthritis.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. NSAIDs are frequently used to treat the pain and inflammation caused by OA.

The Canadian study, published in the journal Arthritis & Rheumatology, looked at nearly 7,750 osteoarthritis patients in British Columbia and compared them with a control group of over 23,000 patients without OA. The average age of the participants was 65 and a little over half were women.

The risk of developing cardiovascular disease was found to be about 23% higher among people with OA than the control group. Researchers attributed about 41% of that increased risk to the use of NSAIDs.

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NSAIDs appeared to play a significant role in several cardiovascular problems. The risk of congestive heart failure was 42% higher among people with OA, followed by a 17% greater risk of heart disease and a 14% greater risk of stroke.

"To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and cardiovascular disease in a large population-based sample," said senior author Aslam Anis, PhD, of the School of Population and Public Health at the University of British Columbia.

"Our results indicate that osteoarthritis is an independent risk factor for cardiovascular disease and suggest a substantial proportion of the increased risk is due to the use of NSAIDs. This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis."

The association of cardiovascular disease with NSAIDs is consistent with previous research.  A large international study in 2017, for example, found that prescription strength NSAIDs raises the risk of a heart attack as soon as the first week of use.

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products, including cold and flu remedies. They are found in so many products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Canada adopted guidelines in 2017 that recommend NSAIDs as an alternative to opioid pain medication. The guideline makes no mention of the health risks associated with NSAIDs, but focuses on their cost effectiveness.

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released in 2016 by the U.S. Centers for Disease Control and Prevention also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

In 2015, the Food and Drug Administration ordered warning labels for all NSAIDs to indicate they increase the risk of a fatal heart attack or stroke. The FDA warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at risk of heart failure. People already diagnosed with heart failure should refrain from using NSAIDs altogether.

Widely Used Painkiller Raises Risk of Heart Problems

By Pat Anson, Editor

The most widely used painkiller in the world should be banned as an over-the-counter drug because it significantly raises the risk of cardiovascular problems and gastrointestinal bleeding, according to a large new study published in the British Medical Journal (BMJ).

Diclofenac is not well-known in the United States, but it is the most widely used non-steroidal anti-inflammatory drug (NSAID) in the world. It is sold both as a prescription and over-the-counter medication under various brand names such as Voltaren, Cambia, Zorvolex and Solaraze.

Researchers looked at healthcare data from over 6 million people in Denmark from 1996 to 2016 and found that those who used diclofenac were 50 percent more likely to have cardiovascular problems such as atrial fibrillation, heart failure and stroke in the first 30 days compared to those who took nothing. Their risk of gastrointestinal bleeding was also higher.

Out of every 1,000 people who used diclofenac, the study estimated that four additional people would develop a major health problem within a year.

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"It is time to acknowledge the potential health risk of diclofenac and to reduce its use. Diclofenac should not be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks," wrote lead author Morten Schmidt, MD, Aarhus University Hospital.

"Treatment of pain and inflammation with NSAIDs may be worthwhile for some patients to improve quality of life despite potential side effects. Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs."

This is not the first time that researchers have warned about the health risks associated with diclofenac and other NSAIDs.

In 2016, researchers at 14 European universities and hospitals, including a number of leading heart specialists, warned that some NSAID’s raise cardiovascular risk and that there is no "solid evidence" the drugs are safe.

Some of the greatest cardiovascular risk comes from a class of NSAIDs known as COX-2 inhibitors. A COX-2 inhibitor called Vioxx was voluntarily pulled from the market by Merck in 2004, but many other COX-2 inhibitors, such as diclofenac, are still widely used for pain relief.   

Another 2016 study published in the BMJ found that use of any NSAID was associated with a 20 percent higher risk of being hospitalized with heart failure. These seven NSAIDs were found to be the riskiest:

  • diclofenac
  • ibuprofen
  • indomethacin
  • ketorolac
  • naproxen
  • nimesulide
  • piroxicam

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products – from headache relievers to cold and flu remedies. They are used in so many different products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The FDA said studies found the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at increased risk of heart failure. Those already diagnosed with heart failure should refrain from using NSAIDs completely.

Opioids vs. NSAIDs for Chronic Pain

 By Roger Chriss, Columnist

The latest shot in the debate over opioids versus non-steroidal inflammatory drugs (NSAIDs) for chronic pain has been fired, with the Minneapolis Star Tribune reporting on a new study that found “patients with chronic pain fared no better with the potentially addictive painkillers than they did with non-opioid meds.”

The research was conducted by Erin Krebs, MD, who is investigating the efficacy of medications for osteoarthritis aspart of a study called the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE).

(Editor's note: Dr. Krebs appeared in a lecture series on opioid prescribing that was funded by the Steve Rummler Hope Foundation, which is the fiscal sponsor of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.)

Her research involved 240 veterans who were treated for back, hip and knee pain with either opioids or non-opioids for 12 months. She presented her findings recently at the Minneapolis VA Medical Center and the Society of General Internal Medicine.

"For long-term treatment of chronic back pain and osteoarthritis pain, non-opioid medication therapy is superior to opioid therapy for both pain and side effects,” Dr. Krebs said.

A summary of the SPACE research states that the “findings showed no significant advantage of opioid therapy compared with non-opioid medication therapy.”

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Naturally, critics of opioid prescribing weighed in.

“If pain doctors still think these medicines are effective, then they have a lot of explaining to do and their competence and professionalism deserve to be challenged,” said Chris Johnson, MD, who is a board member of PROP as well as the Steve Rummler Hope Foundation.

But the study did not show that opioids were ineffective, only that non-opioids were more effective in this particular study. Thus, pain doctors are justified in claiming they are effective. Of course, so are NSAIDs, but this is not a new or surprise finding. Similar results have been obtained before, though only in shorter-term studies.

Dr. Krebs’ results are an important addition to our understanding of which medications are useful for certain types of pain management. In some cases, NSAIDs may be better than opioids, and in other cases, opioids may be better.

But a response like the one from Dr. Johnson is another example of over-generalization and simplification of a complex medical result, and how anti-opioid activists often spin research findings to fit their agendas.  

It also insults the expertise of physicians like Roger Chou, MD,  a Professor at Oregon Health & Science University’s School of Medicine and one of the lead authors of the CDC guidelines; and Sean Mackey, MD, Chief of the Division of Pain Medicine at Stanford University and immediate past president of the American Academy of Pain Medicine.

In a recent Medscape interview, Dr. Chou said, "I don't think there's anything inherently wrong with maintaining somebody on low doses of opioids, as long as it's doing what it's supposed to in terms of helping their pain and function and not causing harm." 

And in a recent Vox interview, Dr. Mackey said, "The fact is if you go looking, there’s clearly data out there that opioids improve pain. These drugs would have never been approved by the FDA if they didn’t."

More importantly, statements like Dr. Johnson’s ignore the difficult challenges that people with chronic pain conditions face.

"Everything we know about pain is that this is a complex biopsychosocial phenomenon,” said Dr. Chou.

Or as Forest Tennant, MD, put it in Practical Pain Management: “A major point to be made about painful genetic diseases is that pain will almost always worsen as the patient ages.”

Chronic Pain is a Complex Problem

Chronic pain management is thus a long-term endeavor requiring as many tools as possible. What works for one person may be ineffective or even contraindicated in another person. NSAIDs may cause intolerable levels of nausea or gastrointestinal pain, and can be contraindicated in some patients because of kidney disease or bleeding disorders. A major study released this week also found that NSAIDs increase the risk of a heart attack.

The converse also holds. Some people do not tolerate opioids well, have too much brain fog or get constipated. And opioids may be contraindicated in a person with respiratory illness or a history of substance abuse. So having an effective alternative such as NSAIDs is important.

Thus, the “risk profile” of each person must be considered. No medication is perfectly safe. According to the FDA, as many as 20,000 people die from NSAID use every year.

At the same time, opioids have risks. Practical Pain Management reported in 2013 that mortality was higher in patients receiving opioids than other analgesics. The risk of addiction to opioids is well-publicized and makes good headlines, but in chronic pain patients it is less than 5 percent.

The unfortunate reality is that pain management is often a lifelong necessity for people who suffer from chronic pain disorders. Such people don’t have the luxury of ideological debates or moralistic disputes. They need a pain toolkit that is as well-equipped as possible, and they have to deal with medication trade-offs in order to address their medical problems.

Prescribing decisions are best left to experienced physicians who know their patients and the medical conditions they have, and can work with them on the risks and benefits of opioids and NSAIDs.

In reality, there is no “versus” here. Opioids and NSAIDs are both valuable tools for chronic pain management. To pretend that one is inherently better than the other is to miss the essential point: Both work and should be available for use as medically appropriate.

Roger Chriss suffers from Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society.

Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

NSAIDs Raise Risk of Heart Attack Within Days

By Pat Anson, Editor

Taking prescription strength non-steroidal anti-inflammatory drugs (NSAIDs) raises the risk of a heart attack as soon as the first week of use, according to a large new study published in The BMJ.

An international teams of researchers analyzed data from eight studies involving nearly 450,000 patients in Canada, Finland and Germany -- 61,460 of whom had a heart attack. They found that taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. Researchers estimated that the overall risk of a heart attack was about 20 to 50% higher when using NSAIDs.

"Given that the onset of risk of acute myocardial infarction occurred in the first week and appeared greatest in the first month of treatment with higher doses, prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses," wrote lead author Michèle Bally, PhD, an epidemiologist at the University of Montreal Hospital Research Center.

The NSAIDs of particular interest to the researchers were ibuprofen, diclofenac and naproxen, as well as the COX-2 inhibitors celecoxib and rofecoxib. COX-2 inhibitors work differently than traditional NSAIDs, by targeting an enzyme responsible for pain and inflammation.

“All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses,” Bally wrote.

Several previous studies have also found that NSAIDs and COX- 2 inhibitors raise the risk of a heart attack, but the exact cause is unknown. Researchers at the University of California Davis reported last year that NSAIDs impaired the activity of cardiac cells in rodents.  

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are in so many different pain relieving products, including over-the-counter cold and flu products, that health officials believe many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered that stronger warning labels be put on NSAIDs to indicate they increase the risk of a heart attack or stroke. The warning does not apply to aspirin.

“There is no period of use shown to be without risk,” said Judy Racoosin, MD, deputy director of FDA’s Division of Anesthesia, Analgesia, and Addiction Products. “Everyone may be at risk – even people without an underlying risk for cardiovascular disease.”

The BMJ study was published the day after Canada released new guidelines that recommend NSAIDs as an alternative to opioid pain medication. The Canadian guideline makes no mention of the health risks associated with NSAIDs, but focuses on their “cost effectiveness.”

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the new guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.

Opioid guidelines released last year by the U.S. Centers for Disease Control and Prevention, which the Canadian guideline was modeled after, also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

Despite those risks, the CDC cited the low cost of NSAIDs and other non-opioid treatments as an “important consideration” for doctors.

“Many pain treatments, including acetaminophen, NSAIDs, tricyclic antidepressants, and massage therapy, are associated with lower mean and median annual costs compared with opioid therapy,” the CDC guideline states.

New Guidelines Offer Little Relief for Back Pain

By Pat Anson, Editor

“Take two aspirin and call me in the morning” doesn’t cut it anymore for low back pain. In fact, very little does.

One in four adults will experience low back pain in the next three months, making it one of the most common reasons for Americans to visit a doctor. But when it comes to treating low back pain, the American College of Physicians (ACP) says the evidence is weak for many pharmaceutical and non-drug therapies.

In fact, the best treatment for acute low back pain may be none at all.

"Physicians should reassure their patients that acute and subacute low back pain usually improves over time regardless of treatment," said Nitin Damle, MD, president of ACP. "Physicians should avoid prescribing unnecessary tests and costly and potentially harmful drugs, especially narcotics, for these patients."

An ACP review committee analyzed dozens of clinical studies to arrive at new guidelines for treating acute back pain (pain lasting less than 4 weeks), subacute back pain (pain lasting 4 to 12 weeks) and chronic back pain (pain lasting more than 12 weeks).  

The ACP recommends that doctors start with non-drug therapies, such as exercise and superficial heat with a heating pad, along with massage, acupuncture, spinal manipulation (chiropractic), tai chi, and yoga. The evidence for the effectiveness of exercise and superficial heat was considered moderate, while the evidence for the other non-drug treatments was considered low quality.

Only when non-drug treatments have failed does the ACP recommend medication for chronic low back pain, starting with non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin. Tramadol (a mild acting opioid) and duloxetine (Cymbalta) are recommended as second line therapies. The ACP says physicians should only consider stronger opioids as a third line therapy when all other treatments have failed.

The evidence for the effectiveness of NSAIDs and opioids was classified as moderate, while the evidence for acetaminophen, benzodiazepines and systemic steroids was considered low-quality.

"For the treatment of chronic low back pain, physicians should select therapies that have the fewest harms and costs, since there were no clear comparative advantages for most treatments compared to one another," Damle said.

The ACP guidelines say surprisingly little about the documented risks associated with NSAIDs, such as cardiovascular and gastrointestinal problems. The guidelines refer only vaguely to “moderate quality evidence” that NSAIDs have “adverse effects.”

Short-term use of opioids for low back pain was linked to increased nausea, dizziness, constipation, vomiting, somnolence and dry mouth. Interestingly, addiction and overdose were not listed as potential risks because they were not studied.

“Studies assessing opioids for the treatment of chronic low back pain did not address the risk for addiction, abuse, or overdose, although observational studies have shown a dose-dependent relationship between opioid use for chronic pain and serious harms,” the guideline states.

The ACP guidelines were released one week after Australian researchers released their own evaluation of NSAIDs in treating back pain. Their study found that NSAIDs reduced pain and disability somewhat better than a placebo, but the results were not statistically important (see “Ibuprofen No Better Than Placebo for Back Pain”).

The ACP calls itself the largest medical specialty organization in the United States. ACP members include 148,000 internal medicine physicians (internists), related sub-specialists and medical students.

The new guidelines are published in the Annals of Internal Medicine.

Ibuprofen No Better Than Placebo for Back Pain

By Pat Anson, Editor

When it comes to treating back pain, anti-inflammatory drugs such as ibuprofen work no better than a placebo, according to new Australian study.

Researchers at the University of Sydney conducted a meta-analysis (a study of studies) of 35 clinical trials involving over 6,000 people with back pain, and found that non-steroidal anti-inflammatory drugs (NSAIDs) provide little benefit. The study was published in the Annals of the Rheumatic Diseases.

NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo,” wrote lead author Gustavo Machado, PhD, of The George Institute for Global Health. “There is an urgent need to develop new drug therapies for this condition.”

Back pain is the world’s leading cause of disability, with about 80 percent of adults experiencing back pain at some point in their lives.

Opioids are usually not prescribed for simple back pain, leaving patients little alternative but over-the-counter pain relievers such as NSAIDs, a class of drugs that includes both aspirin and ibuprofen. NSAIDs are known to raise the risk of gastrointestinal and cardiovascular problems.

The Australian study found that NSAIDs reduced pain and disability somewhat better than a placebo or dummy medication, but the results were not statistically important.

"NSAIDs do not provide a clinically important effect on spinal pain, and six patients must be treated with NSAIDs for one patient to achieve a clinically important benefit in the short-term," wrote Machado. “When this result is taken together with those from recent reviews on paracetamol (acetaminophen) and opioids, it is now clear that the three most widely used, and guideline-recommended medicines for spinal pain do not provide clinically important effects over placebo.”

The study did not evaluate non-pharmacological treatments for back pain, such as exercise, physical therapy or chiropractic care.

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Flu and NSAIDs Increase Heart Attack Risk

By Pat Anson, Editor

With the cold and flu season in full swing, many people take over-the-counter pain relievers like Advil and Aleve to ease their aches and pains, and to help them sleep.

What many don’t know is that they may be increasing their risk of a heart attack.

In a study of nearly 10,000 people hospitalized in Taiwan after a heart attack, researchers found that patients who took non-steroidal anti-inflammatory drugs (NSAIDs) during an acute respiratory infection tripled their risk of an acute myocardial infarction (heart attack).  The study was published in the Journal of Infectious Diseases.

Respiratory infections and NSAIDs were both already known to raise the risk of cardiovascular problems, but this was the first time they were studied together.  

"Physicians should be aware that the use of NSAIDs during an acute respiratory infection might further increase the risk of a heart attack," said lead author Cheng-Chung Fang, MD, of National Taiwan University Hospital.

“This approach should raise clinical concern because NSAIDs use during ARI (acute respiratory infection) episodes is highly common in real-world practice.”

Fang and his colleagues found that using NSAIDs while having a respiratory infection was associated with a 3.4-fold increased risk for a heart attack. The risk was 7.2 times higher when patients received NSAIDs intravenously in the hospital.

Another commonly used pain reliever, acetaminophen, which eases pain in a different way than NSAIDs do, was not evaluated in the study. But researchers say it may be a safer alternative, at least in terms of cardiac risk, for relief from cold and flu symptoms.

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different over-the-counter products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The revised warning does not apply to aspirin. The FDA said people who have a history of heart disease, particularly those who recently had a heart attack or cardiac bypass surgery, are at the greatest risk.

European researchers released an even stronger warning last year, saying there was no solid evidence that NSAIDs are safe.

Exactly how the pain relievers damage the heart is unclear, but a recent study on animals at the University of California, Davis found that NSAIDs reduced the activity of cardiac cells and caused some cells to die.