Use of antiretroviral
drugs can raise blood lipid levels, prompting concerns about increased risk
of cardiovascular disease. Several past studies - including the large D:A:D observational
cohort - have indicated that the risk of myocardial infarction (heart attack)
and other cardiovascular events is elevated in people taking HAART,
especially protease
inhibitors.
Other studies, however, suggest that elevated cardiovascular
risk may be related to HIV infection itself - rather than its treatment - while
some researchers have not seen an elevated risk of heart disease in people with
HIV regardless of treatment status.
In the March 1, 2008 Journal of
Acquired Immune Deficiency Syndromes, Samuel Bozzette and colleagues reported
the latest findings from on ongoing retrospective cohort study of HIV positive
veterans. In the past, Bozzette's team has consistently been among those not finding
evidence of elevated cardiovascular risk related to antiretroviral therapy.
The
present analysis included 41,213 HIV positive patients receiving care within the
U.S. Veterans Affairs (VA) health system between January 1993 and December 2003.
Most (98%) were men, about 50% were black, and 83% were between the ages of 35
and 55. Patients were followed for an average of 4 years, accounting for 168,213
person-years (PY) of follow-up. Results
•
During the follow-up period there were 17,558 total deaths, 1735 in-patient hospital
stays for serious cardiovascular events, and 19,898 occurrences of either death
or admission for serious cardiovascular events or stroke.
•
The all-cause death rate fell from 20.9 deaths per 100 PY of observation in 1995
to 5.2 deaths per 100 PY in 2003.
•
In a patient-level analysis, adjusted hazard ratios
for death dropped "precipitously" for patients of all racial/ethnic
groups, to a low of 0.18 at 72 months of exposure to HAART.
•
Rates of in-patient stays for serious cardiovascular events were stable during
the HAART era.
•
Hazards for serious cardiovascular events remained near 1.0 -- that is, no significant
increase or decrease in risk - with exposure to HAART overall or to specific antiretroviral
drug classes.
•
Hazards for serious cardiovascular events, stroke, or death were only slightly
higher than those for death alone.
•
The risk of cardiovascular events or death did not increase with longer duration
of HAART exposure (24, 48, or 72 months).
•
The only significant risk factors for cardiovascular events or death were older
age and pre-existing cardiovascular disease.
•
The benefits of HAART, including increased survival, continued to increase during
the 8 years since the drugs were introduced in the late 1990s.
Conclusion
Based
on these findings, the investigators concluded, "The risk of serious cardiovascular
events should be factored into individual patient management, but does not pose
an important public health risk."
"We previously concluded that
the benefits of indicated antiretroviral therapy administered in a naturalistic
setting far outweighed any possible increased risk of serious cardiovascular events,"
the authors wrote in their discussion of the results. "After a substantial
increase in the size of the cohort and in the duration and amount of exposure
to antiretrovirals, ecologic data and patient-level models indicate a durable
and increasing survival benefit to HAART over time."
Veterans
Medical Research Foundation and Veterans Affairs Quality Enhancement Research
Initiative for HIV at the Veterans Affairs San Diego Health Care System, San Diego,
CA; Department of Medicine, University of California, San Diego, La Jolla, CA;
RAND Corporation, Santa Monica, CA; Department of Biostatistics, Johns Hopkins
Bloomberg School of Public Health, Baltimore, MD.
3/07/08
Reference S
Bozzette, C Ake, HK Tam, and others. Long-Term Survival and Serious Cardiovascular
Events in HIV-Infected Patients Treated With Highly Active Antiretroviral Therapy.
Journal of Acquired Immune Deficiency Syndromes 47(3): 338-341. March 1,
2008.
Results
