Glaxo 'downplayed' warning on heart-attack risk from Aids drug

The multinational drugs company GlaxoSmithKline (GSK) downplayed an early warning about the rising number of people who have suffered potentially fatal heart attacks following the use of its £600m anti-Aids drug, which is taken daily by tens of thousands of people around the world.

GSK was officially told of the possible risk in May 2005, three years before it issued a statement to its investors saying that the findings of an even stronger potential link between heart attacks and its antiviral drug abacavir are both “unexpected” and “unconfirmed”.

The company also said that it could find no association between abacavir use and heart attacks following a trawl through its internal data, however it failed to mention that its own summary of product characteristics issued when the drug was launched in the late 1990s had actually described “mild myocardial degeneration” in the hearts of mice and rats given the drug for two years.

Some scientists involved with monitoring the safety of Aids drugs are privately furious with GSK for downplaying the significance of one of the biggest safety trials into abacavir – one of several anti-viral drugs taken by Aids patients as part of combined HIV therapy – when the findings were published last month.

“GSK was extraordinarily well prepared in terms of a statement that downplayed the significance of the findings,” said one of the scientists close to the safety study.

“As a consequence, people are now confused and perplexed because they think there is something wrong with the study itself because GSK said that it cannot find any evidence to support the findings of a link with myocardial infarction [heart attacks],” he said.

Alastair Benbow, European medical director for GSK, said that the company takes any new information about the safety of its drugs seriously but it did not want to highlight what may be “spurious observations” relating to abacavir.

The first public sign that abacavir may be linked with increased risk of heart attacks emerged this April when The Lancet published the worldwide “DAD” study into the adverse reactions to anti-HIV drugs, involving clinical observations of 33,347 Aids patients across Europe, Australia and the United States.

The study found that the risk of having a heart attack in patients taking abacavir was almost double that of HIV patients who did not take the drug as part of their combination therapy. The study also found that the risk of heart attacks returned to normal six months after they had stopped taking abacavir.

Independent scientists who analysed the DAD findings said in The Lancet that the data were not strong enough to establish a causal connection because that would have required a different type of study; but they emphasised that the observed increase in the risk of heart attacks was “too strong to ignore”.

The same scientists also pointed out that the studies on which GSK relied for casting doubt on the DAD study were themselves not powerful enough to discount a link between the drug and the risk of heart attacks.

To coincide with the Lancet publication, GSK issued a statement to its investors playing down the association between abacavir and heart attacks, saying that the findings of the DAD study were unexpected and that no possible biological mechanism to explain it has been found.

The statement did not mention that GSK had been made aware three years earlier of a report involving 34 cases of heart attacks in patients taking abacavir. The report or “signal” was sent to the company in May 2005 by an international drug-monitoring centre operated by the WHO in Uppsala, Sweden.

“We sent them the signal and we gave them the chance to comment on it. We received a reply, which was in effect a no-reply. They said ‘thank-you’ and that was all,” said Dr Ralph Edwards, director of the Uppsala Monitoring Centre.

“The purpose of our signal was to do exactly that, to make them aware that there is at least a risk. We expect countries and companies to take it seriously. I am disappointed with GSK’s response in the published literature,” Dr Edwards said.

Dr Benbow said that GSK investigated the Uppsala signal in 2005 and carried out a check of its own internal data, as well as the database of the American Food and Drug Administration, but could not replicate the finding. “So there was not a signal in our internal database or that of the FDA,” he said.

Didier Lapierre, GSK’s vice president of clinical development, said in the statement to investors at the time of the April DAD study that the increased relative risk of heart attacks remained low in absolute terms and that patients should not discontinue treatment without medical advice.

“The DAD findings are unexpected, since we have not seen similar findings in our studies, and we are unaware of any potential biological mechanism that would explain them. In our own analysis of trials involving more than 9,600 patients, no increased risk of heart attack associated with abacavir was found,” Dr Lapierre said.

Scientists involved in the DAD study, however, believe that a possible biological mechanism is that abacavir is converted into a potentially toxic substance called carbovir once it gets into the cells of the heart.

They cite GSK’s own research on animals in support of this hypothesis which found that abacavir is associated with mild myocardial degeneration in the heart tissue of rats and mice given the drug for a period of two years. Dr Benbow said that the company has investigated this hypothesis but has not found any data to support it.

However, Professor Jens Lundgren of Copenhagen University, who led the DAD study, said that his team is actively pursuing this proposal as a possible explanation for the doubling of the risk of heart attacks seen in abacavir patients.

“We do have a sense of what could be the problem. However, we were completely crushed in the GSK media machine when our study came out. GSK were made aware of the findings at the end of last year when we had the first meetings with them,” Professor Lundgren said.

The US Federal Drug Administration and the European Medicines Agency have both said that at present there is no reason to change the prescribing information for abacavir, however they are both reviewing the safety data on abacavir in relation to heart attacks and are expected to issue their conclusions and recommendations later this year.

Suggested Topics
PROMOTED VIDEO
Arts and Entertainment
Eye of the beholder? 'Concrete lasagne' Preston bus station
architectureWhich monstrosities should be nominated for the Dead Prize?
News
Lizards, such as Iguanas (pictured), have a unique pattern of tissue growth
science
Extras
indybest
News
Anna Nicole Smith died of an accidental overdose in 2007
people
Life and Style
food + drink
Arts and Entertainment
'The Great British Bake Off' showcases food at its most sumptuous
tvReview: Bread-making skills of the Bake Off hopefuls put to the test
Extras
indybest
News
ebooksAn evocation of the conflict through the eyes of those who lived through it
Independent
Travel Shop
the manor
Up to 70% off luxury travel
on city breaks Find out more
santorini
Up to 70% off luxury travel
on chic beach resorts Find out more
sardina foodie
Up to 70% off luxury travel
on country retreats Find out more
Have you tried new the Independent Digital Edition apps?
Independent Dating
and  

By clicking 'Search' you
are agreeing to our
Terms of Use.

iJobs Job Widget
iJobs General

EYFS Teacher

£120 - £162 per day: Randstad Education Hull: Randstad Education require an ex...

Year 3 Teacher

£120 - £162 per day: Randstad Education Hull: Year 3 primary supply teacher ne...

SEN Teacher

£100 - £120 per day: Randstad Education Bristol: Supply special educational ne...

Regional ESF Contract Manager

£32500 - £35000 per annum: Randstad Education Birmingham: European Social Fund...

Day In a Page

Middle East crisis: We know all too much about the cruelty of Isis – but all too little about who they are

We know all too much about the cruelty of Isis – but all too little about who they are

Now Obama has seen the next US reporter to be threatened with beheading, will he blink, asks Robert Fisk
Neanderthals lived alongside humans for centuries, latest study shows

Final resting place of our Neanderthal neighbours revealed

Bones dated to 40,000 years ago show species may have died out in Belgium species co-existed
Scottish independence: The new Scots who hold fate of the UK in their hands

The new Scots who hold fate of the UK in their hands

Scotland’s immigrants are as passionate about the future of their adopted nation as anyone else
Britain's ugliest buildings: Which monstrosities should be nominated for the Dead Prize?

Blight club: Britain's ugliest buildings

Following the architect Cameron Sinclair's introduction of the Dead Prize, an award for ugly buildings, John Rentoul reflects on some of the biggest blots on the UK landscape
eBay's enduring appeal: Online auction site is still the UK's most popular e-commerce retailer

eBay's enduring appeal

The online auction site is still the UK's most popular e-commerce site
Culture Minister Ed Vaizey: ‘lack of ethnic minority and black faces on TV is weird’

'Lack of ethnic minority and black faces on TV is weird'

Culture Minister Ed Vaizey calls for immediate action to address the problem
Artist Olafur Eliasson's latest large-scale works are inspired by the paintings of JMW Turner

Magic circles: Artist Olafur Eliasson

Eliasson's works will go alongside a new exhibition of JMW Turner at Tate Britain. He tells Jay Merrick why the paintings of his hero are ripe for reinvention
Josephine Dickinson: 'A cochlear implant helped me to discover a new world of sound'

Josephine Dickinson: 'How I discovered a new world of sound'

After going deaf as a child, musician and poet Josephine Dickinson made do with a hearing aid for five decades. Then she had a cochlear implant - and everything changed
Greggs Google fail: Was the bakery's response to its logo mishap a stroke of marketing genius?

Greggs gives lesson in crisis management

After a mishap with their logo, high street staple Greggs went viral this week. But, as Simon Usborne discovers, their social media response was anything but half baked
Matthew McConaughey has been singing the praises of bumbags (shame he doesn't know how to wear one)

Matthew McConaughey sings the praises of bumbags

Shame he doesn't know how to wear one. Harriet Walker explains the dos and don'ts of fanny packs
7 best quadcopters and drones

Flying fun: 7 best quadcopters and drones

From state of the art devices with stabilised cameras to mini gadgets that can soar around the home, we take some flying objects for a spin
Joey Barton: ‘I’ve been guilty of getting a bit irate’

Joey Barton: ‘I’ve been guilty of getting a bit irate’

The midfielder returned to the Premier League after two years last weekend. The controversial character had much to discuss after his first game back
Andy Murray: I quit while I’m ahead too often

Andy Murray: I quit while I’m ahead too often

British No 1 knows his consistency as well as his fitness needs working on as he prepares for the US Open after a ‘very, very up and down’ year
Ferguson: In the heartlands of America, a descent into madness

A descent into madness in America's heartlands

David Usborne arrived in Ferguson, Missouri to be greeted by a scene more redolent of Gaza and Afghanistan
BBC’s filming of raid at Sir Cliff’s home ‘may be result of corruption’

BBC faces corruption allegation over its Sir Cliff police raid coverage

Reporter’s relationship with police under scrutiny as DG is summoned by MPs to explain extensive live broadcast of swoop on singer’s home