Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen are and have been the go-to “benign” pain medication for doctors and patients alike. Why? They aren’t addictive, and it’s not easy to overdose. Serious side effects like gastrointestinal ulcers and bleeding seemed to be limited to high doses taken for longer periods or time, or to people with significant medical problems.
Even before the era of the opioid epidemic, it was raining NSAIDs, across the country.
In 2004, the manufacturer of the NSAID Vioxx pulled it from the market because the drug was associated with serious cardiovascular problems like heart attacks and strokes. Soon thereafter, a related medication (Bextra) was also discontinued due to cardiovascular risks and potentially fatal skin reactions.
Not all NSAIDs were caught up in that furor. Some prescription NSAIDs (including celecoxib (Celebrex) and some over-the-counter ones (ibuprofen, naproxen) were thought to be relatively safe.
But multiple studies suggest a clear link between all NSAIDs and heart attacks, strokes, and heart failure.
In 2015, the FDA strengthened the recommended warning on all NSAIDs:
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
The latest on NSAIDs and risk of cardiovascular disease
In 2016, European researchers published a study linking NSAIDs to an increased risk of heart failure. They looked at almost seven million people who had been given prescriptions for 27 types of NSAIDs. They found that people taking NSAIDs had a 20% higher risk of heart failure compared to people who were not using them; the higher the dose of NSAIDs, the greater the risk.
A recent Danish study showed an increased risk of cardiac arrest among people who took NSAIDs within the previous month. They identified 29,000 cases of cardiac arrest deaths, and linked these to prior diagnoses and prescription data using population level databases. Careful analysis found that just over 3,300 patients had taken NSAIDs with the month prior to death, and any NSAID use was associated with a 31% increased risk of cardiac arrest. The NSAIDs diclofenac and ibuprofen were associated with a 50% and 31% increased risk, respectively. The risk was even higher for patients with known heart problems (prior heart attack, coronary artery disease, chronic heart failure, arrhythmias) or stroke.
“The findings are a stark reminder that NSAIDs are not harmless,” warned study author Professor Gunnar Gislason in a press conference. “NSAIDs should be used with caution and for a valid indication. They should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors.”
So, now what?
While some doctors recommend caution for patients at risk for heart attack, stroke, and heart failure, NSAIDs are still widely prescribed, even to patients with significant risk factors. This is partly because they are good at relieving many types of pain. And they are easily available, from pharmacies to airports to gas stations to big-box discount warehouses. Right now, anyone can pick up a two-pack of 200-mg ibuprofen tablets with 500 per bottle — that’s 1,000 tablets!
So, does everyone need to stop using all NSAIDs? No. But, some things have to change:
- Patients need to know about these risks, because bad things have happened even to patients without known risk factors for heart disease or stroke.
- People at particularly high risk need to be aware that these drugs (either prescribed or over the counter) may not be safe for them.
- These medications probably should not be available for purchase in massive quantities, as that makes most average consumers think that they’re safe to take in large quantities and for longer periods of time.
Personally, I will continue to take the occasional NSAID, but after writing this piece, I may think twice and wait longer before I do.
Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. New England Journal of Medicine, December 2016.
Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale. Cardiology in Review, July-August 2010.
Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New England Journal of Medicine, March 2005.
Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. New England Journal of Medicine, March 2005.
Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. Journal of the American College of Cardiology, November 2008.
Comparative evaluation of cardiovascular outcomes in patients with osteoarthritis and rheumatoid arthritis on recommended doses of nonsteroidal anti-inflammatory drugs. Therapeutic Advances in Musculoskeletal Disease, August 2014.
Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials. European Journal of Heart Failure, November 2008.
Nonsteroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology, March 2003.
ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESCE. European Heart Journal, July 2012.
Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest: a nationwide case-time-control study. European Heart Journal. Cardiovascular Pharmacotherapy, December 2016.
Rates of Nonsteroidal Anti-Inflammatory Drug Use in Patients with Established Cardiovascular Disease: A Retrospective, Cross-Sectional Study from NHANES 2009-2010. American Journal of Cardiovascular Drugs, January 2017.