A common question from patients goes like this recent message the skeptical cardiologist received through the EMR
My orthopedist prescribed meloxicam for my knee pain. I recall being advised in the past to stop naproxen NSAID. Do you have advice regarding meloxicam?
I wrote about the problems with meloxicam and NSAIDS in cardiac patients in a post a few years ago and although (I think) this patient follows my blog he wasn’t aware of the increased risk of cardiovascular events that occurs with all of these types of medications, many of which are available over the counter.
I’ve updated my prior blog post and spruced it up but little has changed with respect to the side effects of NSAIDs since then. I have been watching Dopesick, an excellent Hulu series that dramatically depicts the role of Purdue Pharma and Oxycontin in our national opioid epidemic and highlights the dangers of opioids when utilized for pain relief.
On the brighter side, topical nonsteroidal creams have shown benefit for arthritic pain and there have been great advancements in the nonpharmacological approach to pain management since 2017.
The patient question I responded to in my original post was about meloxicam and an opioid. In that case, the orthopod told the patient to check with me, the cardiologist but often these drugs are prescribed without the cardiologist or the PCP being made aware.
What follows is an edited version of my original post
Yesterday, a patient called and indicated that he had been prescribed meloxicam and tramadol by his orthopedic surgeon for arthritic leg joint pain. The orthopedic surgeon said to check with me to see if it was OK to take either of these medications.
(Patients, if you want to skip to my answer skip down to the last two sections of the post and avoid the background information.)
What Is The Risk Of Pain Medications?
Cardiologists have been concerned about the increased risk of heart attack and heart failure with nonsteroidal anti-inflammatory drugs (NSAIDs) like meloxicam since Vioxx was withdrawn from the market in 2004.
NSAIDs have long been known to increase the risk of gastrointestinal (GI) bleeding by up to 4-5 fold. Scientists developed Vioxx, a COX-2 inhibitor, hoping to reduce that risk but Vioxx turned out to increase the risk of a heart attack.
Since this revelation, it has become clear that NSAIDs in general increase the risk of heart problems as well as GI problems
This includes the two over the counter (OTC) NSAIDs:
-ibuprofen (in the US marked most commonly as Motrin or Advil, internationally known as Nurofen). For an extensive list of brand names see here.
-naproxen (most commonly sold as Aleve. Per wikipedia “marketed under various brand names, including Aleve, Accord, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Maxidol, Midol Extended Relief, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Pronaxen, Proxen, Soproxen, Synflex, MotriMax, and Xenobid. It is also available bundled with esomeprazole magnesium in delayed release tablets under the brand name Vimovo.)
In 2015 the FDA mandated warning labels on all prescription NSAIDs including
1) a “black box” warning highlighting the potential for increased risk for cardiovascular (CV) events and serious life-threatening gastrointestinal bleeding, ulceration, and perforation;
(2) statements indicating patients with, or at risk for, CV disease and the elderly may be at greater risk, and that these reactions may increase with duration of use;
(3) a contraindication for use after coronary artery bypass graft surgery on the basis of reports with valdecoxib/parecoxib;
(4) language that the lowest dose should be used for the shortest duration possible
5) wording in the warning section that there is no evidence that the concomitant use of aspirin with NSAIDs mitigates the CV risk, but that it does increase the GI risk
Since then, hardly a day goes by without me having a discussion with a patient about what drugs they can safely take for their arthritis.
Prior to 2016 many authorities recommended naproxen as the NSAID of choice for patients with high CV risk. Indeed prior to the publication of the PRECISION study in 2016, I believed that naproxen was the safest NSAID for my cardiac patients. I told them it was OK to use from a CV standpoint but to use the least amount possible for the shortest time in order to minimize side effects.
The PRECISION study compared a COX-2 NSAID (celecoxicib or Celebrex) to ibuprofen and naproxen in patients who required NSAIDS for relief of their joint pain.
cardiovascular death (including hemorrhagic death), nonfatal MI, or nonfatal stroke, occurred in 2.3% of celecoxib-treated patients, 2.5% of the naproxen-treated patients, and 2.7% of the ibuprofen group.
There was no placebo in this trial so we can only look at the relative CV risk of the three NSAIDs and it did not significantly differ.
GI bleeding was less with celecoxib than the other two NSAIDs.
Although this study has flaws it throws into question the greater CV safety of naproxen and suggests that all NSAIDS raise CV risk.
My Current Patient Advice on Cardiac Safety of Pain Meds
Here is a patient information sheet I came across from the Arthritis Foundationotc-pain-medicine-infographic
It’s a reasonable approach for these OTC drugs and I will start handing this out to my patients. We should consider that all NSAIDS have the potential for increasing the risk of heart attack and heart failure, raising blood pressure, worsening renal function and causing GI bleeding.
Therefore, if at all possible avoid NSAIDs.
Acetaminophen (Tylenol) is appears safe from a heart standpoint and overall if you don’t have liver disease it is your safest drug for arthritis. However, it provides no anti-inflammatory effects and often is inadequate at pain relief.
If you must take a NSAID for pain take it at the lowest effective dosage for the shortest time possible.
Treating The Whole Patient
Meloxicam is an NSAID so my patient should, if at all possible, avoid it.
The other drug he was prescribed, tramadol, is an opioid. Opioids have their own set of problems including, most importantly, addiction and abuse.
A recent review concluded
reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date. Accumulating evidence supports the increased risk for serious harms associated with long-term opioid therapy, including overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction; for some harms, the risk seems to be dose-dependent.
As his cardiologist I am concerned about his heart, of course, but a good cardiologist doesn’t just focus on one organ, he looks at what his recommendations are doing to the whole person.
I certainly don’t want to have him become addicted to narcotics in order to avoid a slightly increased risk of a heart attack. On the other hand, the risks of the NSAIDS involve multiple organs, most of which don’t fall in the domain of the cardiologist.
My patient’s risk of taking either the meloxicam or the tramadol is best assessed by his primary care physician, who has the best understanding of his overall medical condition and the overall risk of dangerous side effects from these drugs.
Ultimately, I think the decision of which pain pill to take for chronic arthritis has to be made by an informed patient in discussion with his informed (and informative) primary care physician. Only the patient can decide how much pain he is having and how much risk he/she wants to assume in relieving that pain.