Causing constant pain from inflammation of the joints, arthritis is common and debilitating, especially in older people. Adding to the woes of arthritis sufferers, a recent study has highlighted that commonly used pain relievers for the condition may be damaging heart health.
The destruction of the joints that leads to arthritis has occurred throughout human history, as seen in the bones of early humans from around 4500 BC and in Egyptian mummies from around 2600 BC. The most common type of this illness, osteoarthritis, affects between a quarter and a third of older Australians.
Since it can’t be cured, quack remedies have proliferated and hundreds of “cures” claim almost immediate relief from pain – just search for “arthritis cures” on Google.
The first major drug advance for relieving arthritis pain was the introduction of the anti-inflammatory steroid, cortisone, in the 1950s. The results were dramatic. But the use of higher doses in an attempt to show even better therapeutic responses highlighted a wide range of severe adverse effects, from both cortisone and its derivatives.
Another standard treatment for pain is aspirin (acetylsalicylic acid). Defining how aspirin works – through inhibition of the enzymes that cause inflammation known as cyclooxygenases (COX) – secured the Nobel Prize in Medicine or Physiology and a knighthood for Professor John Vane in 1982. Many different compounds inhibit cyclooxygenases, and this group of compounds is known as the NSAIDs (non-steroidal anti-inflammatory drugs), to separate them from the steroids such as cortisone.
There are two different COX enzymes, known as COX1 and COX2. Aspirin inhibits both enzymes at similar concentrations, and the well-known adverse effects of aspirin, such as gastric bleeding, have been shown to be due to inhibition of COX1.
The market release of selective COX2 inhibitors (rofecoxib – brand name Vioxx and celecoxib – Celebrex) in the late 1990s promised pain relief without gastric bleeding, but rofecoxib (Vioxx) was withdrawn in 2004 after clinical trials on its gastrointestinal effects showed as much as double the risk of increased blood pressure and heart attacks. The increased cardiovascular risk occurred after six to 18 months of treatment. And it was greater in older patients with existing cardiovascular risk factors, who were taking higher rofecoxib (Vioxx) doses.
A summary of all known studies has now been completed to estimate the relative cardiovascular risk of commonly used NSAIDs, especially at low doses as in non-prescription use, over short time periods and in low-risk populations. The research looked at results from community-based controlled studies with NSAIDs that reported on cardiovascular risk. It evaluated 30 case-control studies, which included 184,946 cardiovascular events resulting from all causes. It also looked at data from 21 cohort studies of over 2.7 million individuals taking NSAIDs, doubling the current statistical basis.
Considering only those NSAIDs that have been widely studied, the highest risk of cardiovascular events was shown with rofecoxib (Vioxx), diclofenac (Voltaren) and indomethacin (Indocid). Rofecoxib was withdrawn in 2004 and indomethacin is not commonly used, so the important result is the increased risk with diclofenac, which is available for non-prescription use.
The overall increase in risk with diclofenac (Voltaren) was about 40%, compared with 9% increase with naproxen (Naprosyn), 18% with ibuprofen and 45% with the already-withdrawn rofecoxib. The risk increase with diclofenac (Voltaren) was dose-dependent – 22% at low doses and double that at high doses.
Most studies found that the risk was increased within 30 days of starting on the painkillers. In contrast, naproxen did not produce a significant increase in risk at low or high doses, and there was also no increased risk with ibuprofen at low doses.
This study didn’t evaluate non-prescription use of these NSAIDs, but notes that maximal recommended doses of naproxen (750 mg/day) and ibuprofen (1200 mg/day) show minimal, if any, increases in cardiovascular risk. In contrast, the maximal recommended non-prescription dose of diclofenac (75 mg/day) is similar to the doses increasing cardiovascular risk.
Prescribing must rely on clear clinical evidence, such as that provided in this study, and it’s not just all bad news for people with arthritis. There are effective drugs and doses that need not increase the risk of a heart attack, and patients with existing cardiovascular disease should be more closely monitored when they start on new drugs.