Individual risk factors crucial in determining a patient's risk of heart attack if taking abacavir

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The impact of abacavir treatment on the risk of heart attack varies according to underlying risk factors, investigators show in a study published in HIV Medicine.

Abacavir treatment (Ziagen, also in the combination pills Kivexa and Trizivir) was associated with a 90% increase in the relative risk of heart attack in the D:A:D study. Many patients discontinued treatment with the drug following the publication of these results.

However, an international team of investigators have reassessed the clinical significance of the relationship between abacavir treatment and the risk of heart attack, showing that underlying risk factors are important.

Glossary

cardiovascular

Relating to the heart and blood vessels.

absolute risk

The chance that a person will experience a specific event during a period of time. It is always between 0 and 1 (when expressed as a probability), or between 0 and 100 (when expressed as a percentage).

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).

relative risk

Comparing one group with another, expresses differences in the risk of something happening. For example, in comparison with group A, people in group B have a relative risk of 3 of being ill (they are three times as likely to get ill). A relative risk above 1 means the risk is higher in the group of interest; a relative risk below 1 means the risk is lower. 

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

The researchers wanted to determine the relationship between abacavir therapy lasting five years and the absolute risk of heart attack. In addition, they also wished to see how many patients would need to take the drug for there to be one heart attack.

To do this they took into account individual patient’s individual cardiovascular risk profiles. This involved a consideration of lipid levels, blood pressure, age, smoking, and previous history of cardiovascular disease.

First they assessed the risk for a 40-year-old male with a low-risk profile for cardiovascular disease. The absolute five-year risk of a heart attack for such an individual was 0.1%. Moreover, 1111 patients would need to take abacavir for one individual to experience a heart attack.

However, as an individuals cardiovascular risk profile worsened, their absolute risk of a heart attack increased. In addition, there was a fall in the number of abacavir-patients needed for there to be one additional heart attack.

For example, if a patient had an unfavourable lipid profile (total cholesterol above 6.2 mmol/l) then his absolute five-year risk increased to 0.2%. In these circumstances, the number of patients treated with abacavir for there to be one heart attack was 555.

As the investigators added risk factors, there were further increases in absolute risk accompanied by falls in the number of patients per heart attack.

Therefore, for an individual with high total cholesterol, low HDL cholesterol, who smoked, and had diabetes, high blood pressure and a previous history of heart disease, the five-year absolute risk of heart attack was 15% and one heart attack would be seen per seven patients with such a risk factor treated with abacavir.

‘The clinical implications of this finding are simple – through regular  screening for and proper management of modifiable cardiovascular risk factors which determine underlying risk of MI [myocardial infarction, or heart attack] in HIV-infected patients, it may be possible to increase the number of patients who may be safely treated with a drug that is potentially associated with the development of a serious adverse event”, comment the investigators.

They argue that it is essential that the association between abacavir and a high relative risk of heart attack “is put into context.”

The researchers at the University of Copenhagen have developed an online tool that can be used by doctors and people with HIV to assess the potential impact of abacavir use on cardiovascular risk (link to online tool).

References

Kowalska JD et al. Implementing the number need to harm in clinical practice: the risk of myocardial infarction in HIV-1-infected patients treated with abacavir. HIV Medicine, 11: 200-08, 2010.