A new study on diclofenac and cardiac risk suggests that the risk-benefit analysis for this commonly used non-steroidal anti-inflammatory (NSAID) should now be regarded as completely unfavourable. The implication of such a scientific judgement is that it should be withdrawn from sale altogether, as a public health measure.
Removing a drug from sale is advocated for various reasons from time to time. Some, such as dextropropoxphene seem to be effective, but are found to be no more effective than much safer drugs. Others, such as sibutramine turn out to have unforeseen risks which become apparent with widespread use outside of clinical trials.
Others are harder to understand. Lumiracoxib was a highly effective NSAID which in numerous patients of mine was effective at improving serious musculoskeletal pain where no other drug had been useful. It was, quite literally, a hope for some patients who had none otherwise. The problem was that 8 people out of the 60,000 who took it suffered significant liver damage. Of the 8 cases reported to TGA, 2 survived with liver transplants and 2 died so there was no disputing the seriousness of the liver damage.
The issue for my patients however was that none of them had abnormal liver function tests, and they couldn’t see how the drug should be denied them when they were quite happy to take on the 1 in 7500 chance of serious toxicity.
Isn’t this fair enough?
Fans of lumiracoxib were quick to point out the case of clozapine. Clozapine is a very potent anti-psychotic drug which caused tremendous debate in the mid-1990s due to its ability to improve severe chronic psychosis in previously untreatable patients. Its big drawback was that it had a habit of knocking off peoples' bone marrow and stopping it producing white blood cells. It does this at a rate of around 1 in 100 people who take it. When regulators moved to ban it from sale, they were met with requests from doctors and patients to waive their legal protections and keep taking it, as the patients whose lives were being changed remarkably for the better were arguing that they would rather risk death than go back to the nightmare they had been living before starting clozapine. A reasonable accommodation was reached whereby the drug company paid for the ongoing costs of regular blood tests to monitor the white cell counts and patients taking clozapine were given standard educational materials and asked to consent in writing to the treatment.
Commonly used antibiotics like flucloxacillin and amoxycillin/clavulanic acid have much higher rates and raw numbers of serious liver injury, but have never been close to getting banned. A supreme irony is that diclofenac itself killed more people from liver failure in its first 5 years of use than lumiracoxib ever did!
Beside these figures, simply banning lumiracoxib for a rare and potentially avoidable side effect still rankles as an officious overreaction.
The diclofenac data reported above has been known (at least in the circles I hang out in) for quite a while. Even the Daily Mail in the UK – hardly known as a beacon of common sense – reported this back in 2011 in quite a balanced way. The reason nobody is kicking up too much is that diclofenac is used overwhelmingly for short-term relief from acute musculoskeletal pain, and the additional cardiac risk doesn’t kick in unless you are using it consistently over the medium to long term. It also has quite a short half-life compared to many other NSAIDs, and thus even a daily dose will mean you’re spending most of the time throughout the day without high levels of it in your system. And there are many, many people who benefit from intermittent bursts of diclofenac where little else helps.
The well-characterised excessive cardiac risk of diclofenac should mean that discussions about this risk are built into long-term decision-making about treatments. Potentially risky treatments should be reserved for severe or recalcitrant diseases, and consumers should be kept fully informed. Banning a useful but risky treatment shortchanges consumers as much as allowing them to be exposed to an overly risky one. Informed consent shouldn’t be replaced by bureaucratic paternalism.