April 30, 2009

GSK Studies Show No Increased Heart Attack Risk From Abacavir

An analysis of 52 studies of abacavir (found in Ziagen, Epzicom and Trizivir) by the drug’s maker, GlaxoSmithKline (GSK), found no increased risk for heart attacks in people taking the drug, according to a study published in the May issue of the Journal of Acquired Immune Deficiency Syndromes. These results stand in contrast to results of other studies finding an increased risk of heart attacks among people on abacavir.

All in all, abacavir has had a really rough year. Experts and people living with HIV were taken by surprise when researchers with the international Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study presented follow-up data at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in February showing a 68 percent increase in the risk of a heart attack among people taking abacavir.

Despite intensive ongoing studies, researchers have yet to definitively prove if—or how—abacavir increases the risk of a heart attack. Two other studies have also found at least some increased risk of heart attacks for people on abacavir. This—along with a separate study that found an increased risk of treatment failure in people with very high HIV levels before starting abacavir treatment—led the committee that develops HIV treatment guidelines for the U.S. Department of Health and Human Services (DHHS) to downgrade abacavir from a “preferred” part of HIV regimens in people starting antiretroviral therapy to “alternative” several months ago.

Now, researchers from GSK in the United States and the United Kingdom, led by Cindy Brothers, MSPH, have published an analysis of data from 52 clinical trials and 14,174 HIV-positive patients they collected from abacavir studies sponsored by GSK. In a larger analysis, Brothers’s team compared health outcomes from 9,502 adults who took abacavir with 4,672 adults who did not take abacavir. A second smaller analysis was conducted using data from 3,262 patients who were randomized in a controlled manner to either an abacavir- or non-abacavir-containing regimen. Randomizing people to one arm of a study or another helps ensure that any differences in efficacy or side effects from a drug are actually due to the drug, instead of other factors related to their health.

In both analyses, Brothers’s team found that people taking abacavir had no increased risk of a heart attack or other heart-related problems compared with people not taking abacavir. The authors state their data are an important counterpoint to the earlier D:A:D data, not only because the results were different, but also because the types of studies were different.

D:A:D is a large observational study, which can’t control at the outset for factors that may have led people taking abacavir to have had a higher risk for heart attacks in the first place, and thus it made abacavir seem worse than it is. The GSK analysis, on the other hand, was able to control for some risk factors at the outset in some of the patients, which adds strength to its researchers’ conclusion.

According to Brothers and her colleagues, the numbers in the GSK study are small enough, and the follow-up so short, that it may not have the power to detect a potential heart attack risk increase. They also acknowledge certain heart attack risk factors, such as low-density lipoprotein (LDL) cholesterol levels, were not taken into account before randomizing people to either take or to not take abacavir. Ultimately, the authors state that further research will be needed to settle the controversy.

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