Abacavir Agonistes

June 24, 2011

Paul E. Sax, M.D.

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

The studies on abacavir and its potential association with increased cardiovascular risk have been inconsistent ever since the news first broke at CROI 2008. But recently the data have been swirling around so fast and furious that it seems appropriate to take out this famous Greek epithet.

A summary of some recent notable studies:

  • An FDA meta-analysis presented at CROI this year of randomized clinical trials -- which avoids selection bias -- finds absolutely no association with MI. Note that the analysis includes the studies in this ACTG report, and more.
  • By contrast, a newly published observational VA study -- including 11,000 patients, mostly men -- demonstrates that among HIV therapies, only abacavir is associated with increased risk of cardiovascular events.
  • Up in Montreal, here's another study (n=7,000) with a positive association between abacavir and MI, this time along with several other antiretrovirals (including, oddly, efavirenz -- marking the first time an NNRTI has ever been implicated in CV risk, and frankly raising more questions about study result validity than making me worried about efavirenz). Journal Watch coverage here.
  • Meanwhile, the original VA abacavir study -- the first one to introduce renal disease as an important possible cause of "channeling bias" back in Cape Town -- has just been published, and this one includes even more patients (19,000) than the VA study cited above (I presume there's some overlap). The result? It shows not only no significant association of abacavir with MI, but that abacavir is associated with a reduced risk of cerebrovascular disease (stroke).
  • The editorialist commenting on the paper (Sam Bozzette) examines the numbers carefully and -- somewhat surprisingly in light of the study findings -- writes: "Moreover, the trends tend to support the controversial notion of a differential effect of abacavir [on MI risk]..."
  • And what about that protective effect of abacavir on stroke seen in this study? A Danish study found just the opposite: on investigating possible risk factors for stroke among patients with HIV, the researchers showed that abacavir was associated with increased cerebrovascular events -- and it was the only HIV treatment to earn this honor.

Got that?

Although it's tempting to revert to the last refuge of the researcher, grant writer, and journalist -- the generic "more research is needed" -- I'm pretty sure we've reached a point of diminishing returns on these abacavir-cardiovascular disease studies, at least those of retrospective observational design.

And from a practical, day-to-day patient management perspective, in my view nothing really has changed despite these recent studies. It seems advisable to avoid using abacavir in patients with high cardiovascular risk if there are suitable alternatives (which there usually are), but that stable patients already on the drug should remain on it unless there's a compelling reason to switch.

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.

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This article was provided by NEJM Journal Watch. NEJM Journal Watch is a publication of the Massachusetts Medical Society.


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