Results from the DAD (Data Collection on Adverse Events of Anti-HIV Drugs) study published earlier this year suggested that recent abacavir (ABC) and didanosine (ddI) use were both associated with an increased risk of myocardial infarction.1 In a latebreaker presentation at the International AIDS Conference in Mexico City, Jens Lundgren of Copenhagen presented results from a similar analysis performed on the SMART (Strategies for Management of Antiretroviral Therapy) study data set.
Rates of cardiovascular disease were investigated in the 2752 patients assigned to the continuous ART arm of SMART. Patients in the ART-interruption arm were also included in the analysis of NRTI-use and biomarkers for inflammation and coagulation.
The investigators used three NRTI categories:
1) Abacavir use (but not ddI),
2) ddI (with abacavir or other NRTIs), and
3) NRTIs other than ABC or ddI.
Patient characteristics in the three groups were similar at study entry for age, gender, viral load, median CD4+, percent smokers, percent diabetes, ischemic abnormalities on EKG, prior history of cardiovascular disease, total/HDL ratio and use of lipid lowering, and BP lowering agents.
The authors studied three cardiovascular disease (CVD) endpoints including:
1) Major CVD (clinical and silent MI. The definition of clinical MI was the same as used in the DAD study),
2) CVD - major expanded (major CVD plus peripheral artery disease, CHF, un-witnessed deaths, drug treatment for CAD), and
3) Minor CVD (CHF, peripheral vascular disease or CAD requiring drug treatment.)
The ABC (no ddI) group versus "other NRTI" group showed an excess risk of clinical MI, hazard ratio 4.3 (95% CI:1.4-13.0). Also showing excess risk were major CVD 1.8 (1.0-3.1), and expanded CVD 1.9 (95% CI:1.3-2.9).
When investigating patients with ≥ cardiovascular risk factors, a trend toward excess risk was observed in the abavacir group vs. "other NRTIs" hazard (ratio 3.1, P = 0.1.) The investigators also found higher rates of two biomarkers of inflammation in people taking abacavir. Levels of high-sensitivity C-reactive protein (hsCRP) were 27% higher (P = 0.02) and levels of interleukin 6 (IL-6) were 16% higher (P = 0.02) in the abacavir group compared to those using "other NRTIs".
Limitations of the study were the non-randomized observational study design, overlap between participants in the SMART and DAD studies and the possibility that patients with cardiovascular disease risk factors may have been preferentially placed on abacavir (channeling effect). The results of this study will be published in September 2008 in AIDS.
On Wednesday August 6, Jaime Hernandez from GlaxoSmithKline presented the results of a pooled summary of 54 clinical trials that compared 14683 HIV-infected subjects who received abacavir-containing (n=9639;7845 person years) or non-abacavir-containing regimens (n=5044; 4653 person years). The incidences of coronary artery disease events were low (possibly reflecting the younger age of participants compared with the SMART study). The relative risk for coronary artery disorders comparing abacavir regimens to others, was 0.593 (95% CI: 0.348-1.01) and for myocardial infarction, 0.863 (0.40-1.86) and therefore failed to show an association between coronary artery disease and abacavir use.
Reference:
1. Cutrell A, Brothers C, Yeo J et al. Abacavir and the potential risk of myocardial infarction. The Lancet. 2008; 371(9622):1413.
08/07/08
Abacavir and Cardiovascular Disease: The Debate Continues
Source: Reporting from Mexico City for PRN News: Anita Radix, MD, MPH and Rona Vail, MD