Ask a Clinician
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Ask a Clinician: NRTIs and Heart Attack Risk
In the latest study on HIV and cardiovascular risk, patients taking abacavir (Ziagen, and a component of Epizom and Trizivir) had nearly double the risk of heart attacks, and those taking didanosine (Videx) had about 50 percent greater risk, than those taking zidovudine, stavudine, or lamivudine.
The report was the latest from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, published online April 2 in The Lancet. The Food and Drug Administration (FDA) said it is reviewing the data but has not made any label changes, and said providers should weigh the risks and benefits of all medications they prescribe.
e-News asked Joel Gallant, MD, MPH, associate director of the Johns Hopkins University AIDS Service, to put the study in context.
e-News: How important are these findings?
Joel Gallant, MD, MPH: It’s unexpected, important information from a large, powerful observational database that raises a lot of questions. But it’s not a definitive result in the sense that it’s only been seen in this one study and there’s no biological explanation for the findings.
Also, while the relative risk was large (a 90% increase in risk with abacavir), the absolute risk was low. There weren’t a lot of heart attacks in the study [517 cases of myocardial infarction in a cohort of 33,347 patients].
e-News: This isn’t the first time concerns have been raised about antiretroviral drugs and cardiac risks.
Joel Gallant, MD, MPH: No. In fact, that’s what the D:A:D study was designed to look at. But the cardiac risk for other drugs was readily explainable by metabolic changes caused by HIV therapy such as elevated cholesterol, blood sugar, fat accumulation, and things that we accept as risk factors for heart disease. For abacavir, which doesn’t cause those abnormalities, that doesn’t apply. If the problem was due to metabolic toxicity, then greater exposure to abacavir would increase the cardiac risk. That’s what we see with protease inhibitors, but it’s not what the D:A:D investigators saw with abacavir: risk of heart attack increased once abacavir was started, and was normal in those who had stopped taking abacavir six or more months previously.
If you had to come up with a biological explanation of how abacavir might increase cardiovascular risk in this way, you could postulate that it might cause inflammation, in which case the duration of the exposure wouldn’t be important. But we haven’t seen that before with any other drug, including abacavir.
The study found the same effect with didanosine, but it was a weaker effect. That’s never been seen with didanosine, either.
e-News: What limitations in the study were there that clinicians should be aware of?
Joel Gallant, MD, MPH: This is an observational study, so there’s always the potential for selection bias. Providers might have chosen to use abacavir instead of a protease inhibitor in people who had a high risk for heart disease, leaving those on abacavir at the highest risk. In fact, that’s exactly what happened: cardiovascular risk factors were higher in abacavir-treated patients. However, the risk with abacavir persisted even after adjustment for these risk factors. There’s still the possibility of residual confounding despite adjustment, though if the effect were entirely due to selection bias, you wouldn’t expect the risk to go away after abacavir was stopped.
e-News: What’s the take-home message for clinicians?
Joel Gallant, MD, MPH: I think we should pay attention to the study, but wait to see what happens with other studies before we decide what to do about abacavir. In the meantime, you could argue that somebody at very high risk for heart disease, such as somebody with a strong family history and high lipids, might be better off on tenofovir than abacavir while we wait for more data.
Keep in mind, though, that tenofovir was not included in this study because there weren’t enough people taking it to evaluate its effect. Tenofovir also has potential kidney toxicity. It’s not usually a problem in people with normal renal function, but it might be something to consider in people with diabetes or hypertension, who are at risk for both heart disease and kidney disease. So I don’t think we can conclude that everyone at risk for heart disease should take tenofovir as a result of these data.
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