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
VIDEO
Life & Style
Sampling wine in Turin
food + drink...and abstaining may be worse than drinking too much, says scientist
Arts & Entertainment
Game of Thrones writer George R.R. Martin has been working on the novels since the mid-Nineties
books
Arts & Entertainment
The monster rears its head as it roars into the sky
film
Voices
For the Love of God (2007) The diamond-encrusted skull that divided the art world failed to sell for
its $100m asking price. It was eventually bought by a consortium
which included the artist himself.
voicesYou can shove it, Mr Webb – I'll be having fun until the day I die, says Janet Street-Porter
Sport
Mercedes driver Lewis Hamilton of Britain drives in the rain during the qualifying session of the Chinese Formula One Grand Prix in Shanghai
sport
Extras
indybestFake it with 10 best self-tanners
Arts & Entertainment
Madonna in her music video for 'Like A Virgin'
music... and other misheard song lyrics
News
Much of the colleges’ land is off-limits to locals in Cambridge, with tight security
educationAnd has the Cambridge I knew turned its back on me?
Sport
Steven Gerrard had to be talked into adopting a deeper role by his manager, Brendan Rodgers
sportThe city’s fight for justice after Hillsborough is embodied in Steven Gerrard, who's poised to lead his club to a remarkable triumph
News
peopleOrlando Bloom the pin-up hero is making a fresh start
News
Who makes you happy?
happy listSend your nominations now for the Independent on Sunday Happy List
Life & Style
The North Korean TV advert for Taedonggang beer, that became a YouTube hit
food + drinkAnd what did it take to set up a taste test back in Wiltshire?
Arts & Entertainment
filmLife for Leslie Mann's can be challenging sometimes
Voices
For music lovers: John Cusack with his vinyl collection in 'High Fidelity'
voices...but don't forget rest of the year
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 iPad app?
Independent Dating
and  

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

iJobs Job Widget
iJobs General

Apprentice IT Technician

£150.00 per week: QA Apprenticeships: This company is a company that specializ...

1st Line Technical Service Desk Analyst IT Apprentice

£153.75 per week: QA Apprenticeships: This company is an innovative outsourcin...

1st Line Helpdesk Engineer Apprentice

£150.00 per week: QA Apprenticeships: This company has been providing on site ...

Sales Associate Apprentice

£150.00 per week: QA Apprenticeships: We've been supplying best of breed peopl...

Day In a Page

How I brokered a peace deal with Robert Mugabe: Roy Agyemang reveals the delicate diplomacy needed to get Zimbabwe’s President to sit down with the BBC

How I brokered a peace deal with Robert Mugabe

Roy Agyemang reveals the delicate diplomacy needed to get Zimbabwe’s President to sit down with the BBC
Video of British Muslims dancing to Pharrell Williams's hit Happy attacked as 'sinful'

British Muslims's Happy video attacked as 'sinful'

The four-minute clip by Honesty Policy has had more than 300,000 hits on YouTube
Church of England-raised Michael Williams describes the unexpected joys in learning about his family's Jewish faith

Michael Williams: Do as I do, not as I pray

Church of England-raised Williams describes the unexpected joys in learning about his family's Jewish faith
A History of the First World War in 100 moments: A visit to the Front Line by the Prime Minister's wife

A History of the First World War in 100 moments

A visit to the Front Line by the Prime Minister's wife
Comedian Jenny Collier: 'Sexism I experienced on stand-up circuit should be extinct'

Jenny Collier: 'Sexism on stand-up circuit should be extinct'

The comedian's appearance at a show on the eve of International Women's Day was cancelled because they had "too many women" on the bill
Cannes Film Festival: Ken Loach and Mike Leigh to fight it out for the Palme d'Or

Cannes Film Festival

Ken Loach and Mike Leigh to fight it out for the Palme d'Or
The concept album makes surprise top ten return with neolithic opus from Jethro Tull's Ian Anderson

The concept album makes surprise top ten return

Neolithic opus from Jethro Tull's Ian Anderson is unexpected success
Lichen is the surprise new ingredient on fine-dining menus, thanks to our love of Scandinavian and Indian cuisines

Lichen is surprise new ingredient on fine-dining menus

Emily Jupp discovers how it can give a unique, smoky flavour to our cooking
10 best baking books

10 best baking books

Planning a spot of baking this bank holiday weekend? From old favourites to new releases, here’s ten cookbooks for you
Jury still out on Manchester City boss Manuel Pellegrini

Jury still out on Pellegrini

Draw with Sunderland raises questions over Manchester City manager's ability to motivate and unify his players
Ben Stokes: 'Punching lockers isn't way forward'

Ben Stokes: 'Punching lockers isn't way forward'

The all-rounder has been hailed as future star after Ashes debut but incident in Caribbean added to doubts about discipline. Jon Culley meets a man looking to control his emotions
Mark Johnston: First £1 million jackpot spurs him on

Mark Johnston: First £1 million jackpot spurs him on

The most prize money ever at an All-Weather race day is up for grabs at Lingfield on Friday, and the record-breaking trainer tells Jon Freeman how times have changed
Ricky Gervais: 'People are waiting for me to fail. If you think it's awful, then just don't watch it'

Ricky Gervais: 'People are waiting for me to fail'

As the second series of his divisive sitcom 'Derek' hits screens, the comedian tells James Rampton why he'll never bow to the critics who habitually circle his work
Mad Men series 7, TV review: The suits are still sharp, but Don Draper has lost his edge

Mad Men returns for a final fling

The suits are still sharp, but Don Draper has lost his edge
Google finds a lift into space will never get off the ground as there is no material strong enough for a cable from Earth into orbit

Google finds a lift into space will never get off the ground

Technology giant’s scientists say there is no material strong enough for a cable from Earth into orbit