Regulator still falling short over painkiller warnings

It’s a numbers game: warning of heart attack risk is reassuring but misleading. Flickr/ansik

Millions of people use diclofenac, an over-the-counter painkiller, to relieve pain and inflammation caused by arthritis, backache and other conditions. But on Friday, the UK medicines regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), announced that patients with heart problems should avoid the medicine because it can significantly increase the risk of having a heart attack or stroke.

Diclofenac belongs to a family of drugs called non-steroidal anti-inflammatory drugs, or NSAIDs, which also includes a drug called naproxen and ibuprofen. They are available through prescription and over-the-counter. In 2011, there were nearly 5m prescriptions for diclofenac (about a third of all NSAIDs prescribed), and until 2012 it was the most prescribed NSAID in England.

But while reviews show naproxen isn’t associated with an increased risk of heart attacks and ibuprofen a lower risk, this isn’t the case for diclofenac.

In 2011, a European review showed that patients using diclofenac were 40% more likely) to have a heart attack than those who weren’t. This is the same level of risk as rofecoxib (brand name Vioxx) which was withdrawn in 2004 because of the dangers.

Dangers evident since 2006

Health officials have made the right decision but it’s been too slow coming. As long ago as 2006 there was evidence that diclofenac greatly increased the risk of heart attack.

In 2006 several published studies, including one by us, made this link. The studies were systematic reviews of other smaller studies and included data from both randomised studies, where neither patients nor doctors know who is getting what treatment until the study is completed, and non-randomised ones, where observations are made in real-life situations. Like many decision-making bodies, the MHRA prefers data from randomised studies.

So despite the evidence, and the potential health threat, it was only when two reviews were published in journals this year, including a Lancet review of randomised studies, that the regulator acted.

In the meantime, how many people who have had diclofenac have needlessly suffered a heart attack?

MHRA still falling short on warnings

The regulator tells us that for every 1000 people who take diclofenac, it may cause three extra heart attacks (one fatal) over the number that would have occurred anyway. This doesn’t sound like a lot and it is true in so far as it goes. However, the trouble is that it’s misleadingly reassuring.

This “excess risk” as it is known, applies to people considered in the 2013 Lancet review. These were mostly white women with an average age of 61 and who were in pretty good health; just 9% of these had any history of heart disease and a similar percent for diabetes. So, about eight to nine per 1000 of these people would have had a heart attack a year without diclofenac.

If even this group of people had an excess of three heart attacks a year, what about those with higher levels of cardiac risk who take diclofenac? For them, the excess is a lot more.

Consider people who have already had a heart attack, still smoke a bit, have diabetes and high blood pressure with resulting kidney damage: of 1000 people like this, 50-100 will have a heart attack in the next year. Give them diclofenac – many of them also have arthritis pain - and 70-140 will have a heart attack. That’s an excess of 20-40 heart attacks that did not need to happen if they had been prescribed a safer NSAID like naproxen – and it’s an awful lot more than the three out of a 1000 excess in the MHRA warning.

And people walking around with these levels of cardiac risk aren’t rare. According to the British Heart Foundation), almost 2m people in England aged 65 and over have “serious cardiovascular disease”. If just 10% of these individuals got diclofenac, that’s 4000-8000 extra heart attacks that didn’t need to happen.

And it’s not as if people need to take diclofenac for weeks on end for their risk to rise. There are non-randomised studies showing the risk rises within days of commencing it. Neither does it have to be taken in high doses – the studies have found no “safe” lower dose.

High risk patients and their doctors might be inclined to dismiss the three in a 1000 heart attack excess as worth it for pain relief. They may not take the same view of an excess of 20 or 40 per 1000 people. So even now while the MHRA is providing the correct advice for patients at high risk of heart attacks it is publishing risk estimates that minimise the true hazard.

Diclofenac isn’t a risky drug being prescribed to just a handful of people. However, as concerns about its safety have increased, doctors have voted with their pens. Prescribing has slowed to around 3m prescriptions in 2012. In many cases it has now been replaced by naproxen for which there were almost 6m prescriptions in 2012, compared with under 3m in 2010.

But patients can thank their doctors for paying attention to the clear evidence on risk. There is little for which to thank the regulator.