Earlier this year, the D:A:D study group reported that current or recent use of abacavir or didanosine were associated with elevated rates of myocardial infarction (MI); see HMQ Summer 2008. Since then, other research groups have been attempting to evaluate the cardiovascular effects of NRTIs in their own study populations. The SMART study group recently presented results analyzing MI risks associated with NRTIs.
The SMART study was designed to assess an HIV treatment strategy of continuous ARV therapy compared with CD4-guided ARV treatment. The present analysis evaluated cardiovascular end points and inflammatory biomarkers in 2,752 patients on continuous ARV therapy. Current use of abacavir was associated with an excess risk of cardiovascular events, with a hazard ratio of 4.3 for MI and 1.8 for major cardiovascular disease (CVD) events (a composite end point that included MI, stroke, surgery for CVD, and CVD death) compared with NRTIs other than abacavir or didanosine. Didanosine was not associated with elevated risk of MI. The risk of MI among patients taking abacavir was especially elevated for those who had traditional cardiovascular risk factors, notably those with ≥5 risk factors or those with ischemic changes on baseline electrocardiogram.
In a small subset of patients, biomarker data were collected at baseline; IL-6 and C-reactive protein were noted to be higher for abacavir recipients than for others, though levels of other biomarkers were not elevated.
| Clinical Bottom Line|
These results appear to confirm the findings of the D:A:D group, but the possible role of abacavir in cardiovascular disease events requires further investigation. Despite attempts to control for the fact (confirmed in the D:A:D report) that patients with cardiovascular risks were preferentially treated with abacavir, channeling bias remains a possible explanation for the study findings.
Pending confirmation, clinicians probably should avoid use of abacavir with patients at high risk of CAD events, if appropriate alternatives are available. Additionally, clinicians should work with closely patients to reduce their traditional cardiovascular risk factors.
The DHHS Adults and Adolescents Antiretroviral Treatment Guidelines Panel designates abacavir as a "preferred" component in initial therapy (for patients who test negative for HLA-B*5701), and states that ARV selection should be individualized for each patient.