Vioxx, a COX-2 inhibitor used as an anti-inflammatory and a painkiller was withdrawn from US markets in 2004 because of known cardiovascular risks—those who took it suffered blood clots and strokes, even though it was effective for pain reduction. This week, a study published in the British Medical Journal indicates that another common anti-inflammatory, diclofenac (also known by the brand name Voltaren) may cause similar problems. Diclofenac is also a selective COX-2 inhibitor, and is the most commonly used NSAID around the world, as it is commonly available over-the-counter in most countries. The authors of the study used the data of 6 million Danish adults over two decades (1996-2016) to create virtual trials in which they compared the 12-month health outcomes of patients who started taking diclofenac for pain as compared to those who took acetaminophen (Tylenol), naproxen (Aleve), and those who took nothing at all. The adults taking diclofenac were 50 percent more likely to have a cardiac event within a month than those who took no pain medication. They were also at a higher risk than those who took the other pain medications.
The authors suggest that this may be because diclofenac is prescribed at relatively high doses to be effective for pain since it has such a short half-life. The concentration of diclofenac in the plasma after high doses therefore exceeds the amount needed to inhibit COX-2 and so ends up inhibiting COX-1 as well. After the concentration of diclofenac decreases, the COX-1 effect subsides while the COX-2 inhibition continues. This selective inhibition of COX-2 leads to blood clots by inhibiting prostacyclin (clotting inhibitor) production without affecting thromboxane (clotting promoter) production. The researchers recommend that diclofenac only be prescribed by physicians (rather than being available OTC) and that providers consider the danger of increased clotting on a patient-by-patient basis to avoid unnecessary risk.
Do you think the same risk is present if just using the topical gel? I know a lot of patients who use diclofenac gel on their knees or shoulders, and I wonder if the risk is the same. It's local relief, but there are still warnings for abdominal pain and GI upset. It's also interesting that they are just coming out with this study because if diclofenac is deemed a NSAID, it already has the possibility of leading to a cardiac event or stroke in patients. An article by Harvard Health states that the FDA has strengthened the warning that NSAIDs increase heart attack, and it was written back in 2015 (https://www.health.harvard.edu/blog/fda-strengthens-warning-that-nsaids-increase-heart-attack-and-stroke-risk-201507138138).
ReplyDeleteI wonder what the next steps will be, or the next drug, for pain relief for patients.
I think that since the gel is working though the same pathway, there may be some risk, but since the study seemed to show that it was dose-dependent (ie the high dose needed for effect was causing the problem) the relatively low dose in the gel may cause fewer problems. The study was specifically regarding the pill form, however.
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