Update on Inflammation and Cardiovascular Risk in People With HIV

VA Study Fingers Kidney Disease as a Major Predisposing Factor for Heart Attacks

Researchers with the Veterans Administration (VA) system in the U.S. have amassed a large dataset collected from nearly 20,000 HIV-positive people who sought care and treatment. These researchers note that rates of heart attack appear to be declining recently among HAART users in the U.S., particularly those from northern California, so they are puzzled by the reports of an increased heart attack risk in people who have used abacavir.

VA researchers decided to analyse their database for any possible link between the use of abacavir and the development of a heart attack or stroke. They noted that in addition to traditional CVD risk factors, conditions such as chronic kidney disease and, in some studies, hepatitis C virus (HCV) infection also increase the risk for heart attack or stroke. What's more, VA researchers underscored the following: Because the anti-HIV drug tenofovir can cause kidney toxicity, the presence of pre-existing chronic kidney disease in some people might have caused doctors to prescribe abacavir instead of tenofovir. This may have resulted in a large proportion of abacavir users having an increased risk for heart attack because of a pre-existing condition -- chronic kidney disease. To explore these and other issues, VA researchers conducted a study.

Study Details

The VA team analysed health-related information collected between 1996 and 2004. They divided participants into several groups based on their treatment as follows:

• HAART containing abacavir
• HAART without abacavir
• taking only one or two anti-HIV drugs (usually these would be nukes)
• not taking any anti-HIV treatment

This last group of people not taking medicines was used as control, or comparison, group.

Researchers analysed medical records of 19,424 HIV-positive people whose average age was 46 years and who had been monitored for at least four years.

Results

The VA team found that 80% of people in its database used anti-HIV drugs and the following events occurred during the study period:

• heart attacks -- 278 case
• stroke -- 868 cases

The VA team found that people with heart attacks, compared to people who did not have a heart attack, were more likely to fit the following profile:

• be older (51 years vs. 46 years)
• have diabetes
• have high blood pressure
• have abnormal cholesterol levels
• have chronic kidney disease; that is, an eGFR (estimate-glomerular filtration rate) of 60 or less. [For more information about the kidneys and how doctors assess kidney health using eGFR, see TreatmentUpdate 174.]

Heart Attack and Treatment

The VA team noted that rates of heart attack remained relatively stable over the study period. When they examined the data, looking at the possible impact of treatment on heart attack, here's what they found.

• HAART containing abacavir -- no significantly increased risk of heart attack
• HAART without abacavir -- no significantly increased risk of heart attack
• taking only one or two nukes -- a 44% increased risk of heart attack

Researchers found that the use of these particular medicines had no significant effect.

Heart Attack and Chronic Kidney Disease

• People who had an eGFR below 60 had a 400% increased risk of heart attack.
• People who had an eGFR between 60 and 89 were just beyond the threshold of statistical significance for an increased risk of heart attack.
• People who had a normal eGFR (90 or greater) did not have an increased risk for heart attack.

Stroke and Treatment

When they examined the data, looking at the possible impact of treatment on stroke, here's what the VA researchers found:

• HAART containing abacavir -- no significantly increased risk of stroke
• HAART without abacavir -- no significantly increased risk of stroke
• taking only one or two nukes -- no significantly increased risk of stroke

Did Pre-Existing Conditions Affect Prescription?

Researchers found a highly statistically significant link between the presence of chronic kidney disease and the nuke that doctors prescribed patients. For example, patients given abacavir were statistically more likely to have chronic kidney disease than patients given tenofovir. Because chronic kidney disease places people at increased risk of heart attack, the relative excess prescriptions of abacavir to people with kidney disease may have led to the false conclusion that the use of abacavir caused heart attacks.

The VA study is not perfect -- it is a retrospective study, which looks back at events that already happened. But the VA collected data on heart attacks between 1996 and 2004, while the DAD study only started collecting data on heart attacks in 1999.

The VA researchers suggest that in some other studies, such as DAD, the role of chronic kidney disease in abacavir users has not been fully assessed and this might have led the study teams to conclude that the use of abacavir was somehow linked to the development of a heart attack.

Reference

1. Bedimo R, Westfall A, Dreschler H, et al. Abacavir use and risk of acute myocardial infarction and cerebrovascular disease in the HAART era. In: Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town, South Africa. Abstract MOAB202.