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Meta-analysis Shows Abacavir Has No Effect on Cardiovascular Adverse Events: Presented at AIDS 2010
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By Evelyn Harvey
http://www.pslgroup.com
VIENNA -- July 21, 2010 -- An effective component of HIV drug regimens, abacavir has been subject to controversy following its apparent association with cardiovascular adverse events in several observational studies and in 1 randomised controlled trial (RCT). However, other RCTs and aggregated safety data contradict this.
A meta-analysis presented here on July 21 at the 18th International AIDS Conference 2010 potentially clarifies the situation -- no link between abacavir and cardiovascular risk was found using data from 29 RCTs.
"Observational studies are prone to biases and should be interpreted with caution given the potential for confounding," said Mario Cruciani, MD, University of Padua, Padua, Italy.
Therefore, Dr. Cruciani and colleagues selected 29 RCTs of which 19 were identified via systematic review of the literature, and 10 were unpublished trials conducted by the manufacturer of abacavir.
Studies were selected where abacavir-containing regimens were compared with non- abacavir regimens, for a minimum of 24 weeks' exposure to abacavir.
The researchers analysed rates of myocardial infarction (MI), death, and adverse events (both overall and requiring discontinuation), as well as the proportion of patients with viral loads below either 50 or 200 to 500 HIV RNA copies/mL at weeks 48 and 96. Data from 9,611 participants were included in the meta-analysis.
In terms of virological outcomes, abacavir was similar to all control groups with 1 exception -- abacavir was favoured over tenofovir at 48 weeks in a subgroup of individuals with baseline viral loads >100,000 copies/mL.
Examining adverse event data, the researchers found that abacavir use did not increase the occurrence of MI (P = .36) or the overall mortality (P = .17). The rate of adverse events requiring discontinuation was also unchanged between abacavir groups and controls (P = .19).
The authors acknowledged that previous observational studies linking abacavir to cardiovascular risk followed patients for longer than the studies included in this meta-analysis. However, only recent (<6 months) use of abacavir was associated with risk in previous studies.
The researchers also pointed to a failure to allow for the confounding factor of kidney disease, which may be linked to cardiovascular risk in patients with HIV.
[Presentation title: Abacavir Use and Cardiovascular Disease Events: A Meta-Analysis of Published and Unpublished Data. Abstract WEPE0121]
Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data
M. Cruciani1, V. Zanichelli2, G. Serpelloni1, O. Bosco1, R. Mazzi1, S.G. Parisi2
1HIV Center, Verona, Italy, 2University of Padua, Padua, Italy
Background: The use of abacavir (ABC) has been associated with an increased risk of cardiovascular disease within the setting of cohort studies and of a randomized trial (RCT). However, no excess risk of myocardial infarction with ABC therapy has been observed in others RCTs and in the aggregated clinical trials database maintained by the manufacturer of ABC. The principal aim of this study is to combine all the evidence from RCTs by means of meta-analysis to estimate the effect of combined antiretroviral therapy (cART) containing ABC on major cardiovascular event.
Methods: A comprehensive search of the available literature was carried out. Information about unpublished trials was attempted by contacting drug manufacturers. Data extracted included: any cardiovascular events and overall mortality. We used a conventional Mantel-Haenszel method, with odds ratio (OR) and 95% confidence intervals (CI) or, in the presence of heterogeneity, a random-effect model.
Results: We obtained data from 36 RCTs conducted from 1996 to 2009, comparing cART with ABC to other NRTI . Data of 13 RCTs with at least 24 wks of ABC exposure were available from HIV data repository of the manufacturer of ABC. Data on cardiovascular events were available from 16 RCTs (5,051 pts; 1,045 from published trials and 4,006 from data repository), data on mortality from 23 published RCTs (6,372 pts). Compared to the controls, ABC use did not increase the occurrence of major cardiovascular events (OR, 1.10; 95% CI, 0.56-2.10), and the overall mortality (OR, 1.84; 95% CI, 0.71-4.76).
Conclusions: Observational studies are prone to biases and should be interpreted with caution given the potential for confounding. By contrast, randomized trials provide stronger evidence than do observational studies. Our meta-analysis was based on RCTs, and did not show an increase in the occurrence of major cardiovascular events and overall mortality in ABC recipients.
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