GSK says its abacavir trials show no heart attack risk

GlaxoSmithKline – the manufacturer of abacavir (Ziagen) – says its own data on the drug show no suggestion of any increased risk of myocardial infarction (heart attack), in contrast to findings from a recent large international cohort study.

The data have received advance online publication as a letter on The Lancet website - alongside the D:A:D study (Data Collection on Adverse Events of Anti-HIV Drugs), and will appear in a future edition of The Lancet.

That study suggest abacavir increases the risk of MI by 90% and didanosine (Videx) by 49% and was presented in February 2008 at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston and reported here

The findings were unexpected - although the increased risk due to both abacavir and didanosine disappeared within six months of the drugs being discontinued, and no similar effect was seen with the other drugs studied in D:A:D – zidovudine (AZT) and stavudine (Zerit).

The letter from GSK says its own analysis of data pooled from 54 clinical trials did not suggest an increased risk of MI with abacavir.

Dr Didier Lapierre from GSK said: "We did not find a result consistent with that of D:A:D. Nonetheless GSK takes the D:A:D finding seriously and is committed to understanding these data more fully and to communicating openly with treating physicians and regulatory agencies globally."

But GSK’s analysis has come in for criticism in an accompanying Lancet editorial, written by cardiologist Dr James Stein of the University of Wisconsin School of Medicine and Public Health and HIV physician researcher Dr Judith Currier of the University of California David Geffen School of Medicine.

They say the findings from D:A:D were observational – that is the trial was not designed to specifically look at this effect – and should therefore be treated with caution.

But the magnitude of the effect among those people at highest risk of heart disease is so great it cannot be ignored, they insist.

‘In these individuals – about 6% of the D:A:D cohort – one additional MI would be expected for every 11 treated with abacavir or every 20 treated with didanosine for five years,’ they say.

‘On [this] basis, alternatives to abacavir and didanosine in high-risk patients should be considered [but] the decision to switch antiretroviral therapy must be made cautiously.’

Those deemed at high risk would be those with high cholesterol or blood pressure, diabetes, smokers or those with a family history of heart disease.

Commenting on GSK’s analysis they say: "Although the low overall rates of MI are somewhat reassuring [the] analysis is not powered to detect meaningful differences.

‘It was based on only 18 MIs and the limitations of summaries of pooled data for uncommon events in studies not designed to detect them are well known."

They add that any available data on heart disease from antiretroviral clinical trials should be submitted for peer review so the trial design and analysis can be described in detail and their conclusions fully interpreted.