Several years ago researchers working with a large observational database called DAD (with more than 33,000 HIV-positive people) announced that they had found a link between the use of the anti-HIV drug abacavir (Ziagen and in Kivexa, Epzicom and Trizivir) and an increased risk for heart attack. They also announced that they found a link between the use of the anti-HIV drug ddI (Videx EC, didanosine) and an increased risk for heart attack. Several other studies have not found this link with abacavir (and none have found a link with ddI), and so the initial findings from DAD have become deeply controversial for at least these and other reasons, as follows:
Finally, at least two large databases, the French Hospital Database (with more than 77,000 HIV-positive people) and the Veterans Administration (almost 20,000 HIV-positive people), have not found an association between the use of abacavir and the development of heart attack or stroke. A recent analysis of Kaiser Permanente, a large database in northern California with records on more than 35,000 HIV-positive people, has found that the risk of heart attack and stroke has significantly decreased over time (1996 to 2008), falling to levels seen in HIV-negative people.
In 1989, doctors in France established the French Hospital Database (FHDB), which has collected health-related information on more than 77,000 HIV-positive people. Researchers working in HIV sought to assess rates of heart attacks among HIV-positive patients in France and looked at cases between the years 2000 and 2008. During this time they found 278 cases of heart attack, all of which were confirmed by a research cardiologist. These 278 cases occurred among more than 77,000 people, about 80% of whom were using HAART (personal communication, Dominique Costagliola, PhD).
Lead researcher Dominique Costagliola recently reanalyzed the FHDB's large dataset to find any links between the occurrence of a heart attack and any of the following anti-HIV drugs commonly called nukes:
Overall, there was no statistically significant connection between the use of any of these nukes -- including abacavir -- and a heart attack.
It is important to note that French researchers made sure to take into account other conditions that are known to cause heart attacks and which could have biased their results and caused them to draw false conclusions, including these:
The French researchers also took into account the use of the following anti-HIV medicines, in case they might have played a role in heart attacks observed in abacavir users.
Researchers found that the use of these particular medicines had no significant effect.
The French researchers found that out of 278 abacavir users who had a heart attack, only five had no risk factors for cardiovascular disease (CVD). This means that 98% of abacavir users who had a heart attack had at least one risk factor for cardiovascular disease. Indeed, a large proportion (nearly 40%) of the 278 people had three or more risk factors for CVD.
Other studies have found that having HIV infection appears to be a risk factor for CVD. Among the 278 abacavir users who developed a heart attack, 56% had a detectable viral load. This could have played a role in the development of heart attack.
Going beyond previous analyses, French researchers specifically checked for the use of cocaine and other substances or behaviours, such as injecting drug use, in abacavir users who had a heart attack. Cocaine, which can be snorted or injected, is a stimulant and can stress the heart. Because injection drug use is one of the means by which HIV is transmitted, it is not surprising that some HIV-positive people use cocaine and other illicit drugs.
To find out if these drugs played a role in some of the heart attacks seen in some abacavir users, the FHDB did another analysis. When the researchers took into account the use of cocaine or other illicit substances among people who were prescribed abacavir, again they found no link between the use of abacavir and heart attacks. Furthermore, the researchers found that many of the people who used cocaine and other illicit drugs also had traditional CVD risk factors. Perhaps their use of cocaine in the setting of other CVD risk factors might have greatly increased their risk for having a heart attack.
In conclusion, Dr. Costagliola noted that traditional risk factors (high cholesterol, blood pressure and so on) in concert with cocaine and injection drug use are "very strong risk factors for [heart attack] in HIV-1 infected patients."
Therefore, based on the most recent analysis of the large French Hospital Database, particularly taking into account the use of cocaine and other illicit substances, it seems that exposure to abacavir is not statistically linked to the development of a heart attack.
However, doctors caring for HIV positive patients who use cocaine or stimulants or inject illicit substances may wish to avoid the use of abacavir in this population.
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