Bisher AKIL, MD

Abacavir and Risk for Heart Disease

In Heart on March 23, 2009 at 2:04 pm

In February 2008, findings from the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study indicated that the incidence of myocardial infarction increased nearly two-fold with recent (less than 6 month) use of abacavir. Subsequently, a retrospective analysis from the SMART (The Strategies for Management of Antiretroviral Therapy) study revealed similar results. In the ensuing year, data from various studies fell on both sides of the subject. This year at the 16th Conference on Retroviruses and Opportunistic Infections (CROI), four different studies were presented, adding more to the controversy:
1. An updated analysis from the DAD Study, involving >178,000 person-years of follow-up, confirmed that recent abacavir use was strongly associated with increased risk for myocardial infarction (MI), whereas cumulative exposure was only modestly associated with myocardial infarction.
2. A case-control study from the French Hospital Database group, involving 289 MI cases and 865 controls, showed that recent, short-term use (<1 year) of abacavir was significantly associated with MI risk
3. In the STEAL Study from Australia, 357 patients with viral loads <50 copies/mL who were HLA B5701–negative had the NRTIs in their current regimens switched to either abacavir/3TC (Epzicom) or tenofovir/FTC (Truvada). At week 96, abacavir/3TC was associated with significantly more cases of serious CVD (8 vs. 1)
4. In contrast to these data, a pooled analysis of five ACTG studies, all conducted in patients initiating antiretroviral therapy (ART), showed no evidence of a link between recent abacavir use and cardiovascular outcomes.
The mechanism of this association was also a subject of speculation and more controversy: The manufacturer-sponsored, randomized HEAT Study, 96-week changes in inflammatory markers (C-reactive protein and interleukin-6) and endothelial activation markers (vascular cell adhesion molecule-1) did not differ significantly between patients who started ART with abacavir/3TC and those who started with tenofovir/FTC. Similar null results were seen in biomarker analyses from the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study and also from ACTG 5095. However, two small studies did suggest that abacavir use was associated with impaired brachial dilatation and increased platelet aggregation.
In reviewing the data from the conference, Dr. Peter Reiss (Associate Professor of Medicine, Academic Medical Center at the University of Amsterdam, and a member of the DAD Study Group), he noticed that studies showing a relationship between abacavir and heart disease had patients that tend to be 7-10 years older than other studies and are usually receiving antirotriviral therapy (ART) with viral suppression.
Comments: This association remains unclear. Furthermore there is no clear etiology ( or more likely several etiologies). People with risk for coronary artery disease (smoking, over 45 years of age, male,…etc) need be evaluated carefully for the choice of medications. What is clear: no one treatment fits all, and the risk for heart disease should be assessed carefully in each individual. Treatment for underlying problems (such as hypertension, hyperlipidemia, obesity, smoking,…etc) much be addressed and treated as aggressive as one treats HIV itself_ BA.

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