GSK says its abacavir trials show no heart attack risk

This article is more than 14 years old. Click here for more recent articles on this topic

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

Glossary

powered

A study has adequate statistical power if it can reliably detect a clinically important difference (i.e. between two treatments) if a difference actually exists. If a study is under-powered, there are not enough people taking part and the study may not tell us whether one treatment is better than the other.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

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.

References

D:A:D study group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. The Lancet. Published online 2nd April 2008.

Stein JH and Currier JS. Risk of myocardial infarction and nucleoside analogues. The Lancet. Published online 2nd April 2008.

Cutrell A et al. Abacavir and the potential risk of myocardial infarction. The Lancet. Published online 2nd April 2008.