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Home > Treatment > HIV Meds Quarterly > Spring 2009 > Abacavir and Myocardial
Abacavir and Myocardial Infarction Risk: Additional Data
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The question of whether abacavir increases the risk of myocardial infarction (MI) initially arose with a study from the D:A:D cohort last year, followed by conflicting analyses from other studies (see previous HMQ reports Abacavir and Didanosine Associated with Increased Risk of Myocardial Infarction and Abacavir and Risk of Myocardial Infarction: The SMART Study). In the intervening time, several studies have attempted to clarify this important issue and to elucidate possible causative mechanisms. At the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal in February this year, findings from a number of investigations were presented, including:

transparent gifgrey bulletAn update from the D:A:D Study with data from one additional year of follow-up; the conclusion about abacavir was the same: current or recent use is associated with increased rates of MI (relative rate: 1.68).(1) Importantly, the study compiled sufficient data this year to allow analysis of tenofovir; tenofovir was not associated with increased MI risk. This provides further evidence against the theory that channeling bias is responsible for the abacavir findings.
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transparent gifgrey bulletA case-control study from the French Hospital Database found that current or recent abacavir use was associated with MI risk (odds ratio: 1.97), but only for subjects who had been on abacavir ≤1 year (in patients on abacavir >1 year, or in those with past use of abacavir, there was no statistically significant increased risk of MI). Tenofovir was not associated with MI risk.(2)
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transparent gifgrey bulletA 96-week simplification study, in which subjects with suppressed HIV RNA were randomized to switch the NRTI components of their antiretroviral treatment (ART) regimens to abacavir/lamivudine or tenofovir/emtricitabine, found higher rates of cardiovascular disease in the abacavir arm (2.2 vs 0.3; p = .046).(3)
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transparent gifgrey bulletOn the other hand, analysis of data from 5 AIDS Clinical Trials Group randomized controlled trials of initial ART regimens found no significant associations between recent abacavir use and MI or severe cardiovascular disease.(4)
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In evaluations of possible mechanisms to explain the observed adverse cardiovascular effects of abacavir, the following results were reported:

transparent gifgrey bulletA small study of patients with suppressed HIV viremia demonstrated endothelial dysfunction in those on abacavir-containing ART, as measured by impairment of flow-mediated vasodilation of the brachial artery.(5)
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transparent gifgrey bulletAnother small study showed increased platelet reactivity in patients taking abacavir, compared with those on other NRTIs.(6)
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transparent gifgrey bulletMeasurement of biomarkers from the MACS and WIHS cohorts showed no significant changes in C-reactive protein, d-dimer, or IL-6 after initiation of abacavir.(7)
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Clinical Bottom Line

Although the clinical studies continue to yield conflicting results, it is becoming a bit clearer that the studies with larger, more robust data sets tend to find an association between abacavir and MI risk. Additionally, there now are some hints about the mechanism of that effect. However, the questions about abacavir and possible cardiovascular risks remain puzzling; it is hoped that additional research will clarify the issue. For an excellent overview of current knowledge about abacavir and cardiovascular risk, please view the webcast of Dr. Peter Reiss's plenary session presentation at CROI.(8)

Meanwhile, clinicians should continue to work with patients to decrease their traditional cardiovascular risk factors, and to control HIV infection, which itself is a risk for atherosclerosis.

References

  1. Lundgren J, Reiss P, Worm S, et al; Aquataine, AHOD, ATHENA, INSIGHT, EuroSIDA, ICONA, Nice, SHCS, St Pierre cohorts, and D:A:D Study Group. Risk of myocardial infarction with exposure to specific ARV from the PI, NNRTI, and NRTI drug classes: The D:A:D Study. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 44LB.
  2. Lang S, Mary-Krause M, Cotte L, et al; Clinical Epi Group of the French Hospital Database on HIV. Impact of specific NRTI and PI exposure on the risk of myocardial infarction: a case-control study nested within FHDH ANRS CO4. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 43LB.
  3. Cooper D, Bloch M, Humphries A, et al; STEAL Study Investigators. Simplification with fixed-dose tenofovir/emtricitabine or abacavir/lamivudine in adults with suppressed HIV replication: The STEAL Study, a randomized, open-label, 96-week, non-inferiority trial. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 576.
  4. Benson C, Ribaudo H, Zheng E, et al; ACTG A5001/ALLRT Protocol Team. No association of abacavir use with risk of myocardial infarction or severe cardiovascular disease events: results from ACTG A5001. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 721.
  5. Hsue P, Wu Y, Schnell A, et al. Association of abacavir and HIV disease factors with endothelial function in patients on long-term suppressive ART. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 723.
  6. Satchell C, O'Connor E, Peace A, et al. Platelet hyper-reactivity in HIV-1-infected patients on abacavir-containing ART. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 151LB.
  7. Palella F, Gange S, Elion R, et al. Inflammatory markers among abacavir and non-abacavir recipients in the Womens' Interagency HIV Study and the Multicenter AIDS Cohort Study. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 150LB.
  8. Reiss P. Abacavir and cardiovascular risk. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 152.
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