Treatment with the anti-HIV drug abacavir does not increase
the risk of heart attack, US investigators report in the April 1st
edition of Clinical Infectious Diseases.
Researchers analysed heart attack rates in over 5000
patients who started antiretroviral therapy in randomised trials.
The absolute risk of heart attack was low, and there was no
difference in the rate of heart attack between patients treated with abacavir
and those taking non-abacavir combinations.
“We did not
find evidence of increased short-term or long-term risk of MI [myocardial
infarction, or heart attack] or serious CVD [cardiovascular disease] events
associated with abacavir use as part of initial ART [antiretroviral therapy],”
comment the investigators.
Traditional factors for cardiovascular disease such as older
age and smoking were the main risks for heart attack, and the researchers
recommend that these should be the focus for health promotion interventions.
The findings of the study call into question those of other
research.
Results from the D:A:D and SMART studies showed that therapy
with abacavir (Ziagen, also in the
combination pills Kivexa and Trizivir) was associated with a
substantial increase in the relative risk of heart attack.
However, GlaxoSmithKline (GSK), the makers of abacavir,
failed to find this association in their randomised trials involving the drug.
Nevertheless, treatment guidelines now recommend that individuals with
established risk factors for heart disease should not be treated with abacavir.
A US research team lead by Dr Heather Ribaudo of the Harvard
School of Public Health were concerned about this apparent discrepancy in
research findings, and also noted that a substantial increase in the relative
risk could nevertheless still mean that the absolute risk of heart attack
associated with abacavir remained low.
They therefore analysed the results of six clinical trials
involving 5056 patients starting HIV therapy for the first time to establish if
treatment with abacavir increased the absolute risk of heart attack on both the
short-term (one year) and long-term (up to six years). The studies recruited
patients between 1998 and 2007 and follow-up data were collected until June
2009.
The randomised design of the studies included in the
investigators’ analysis was a major strength. This meant that the studies were
not limited by many of the confounding factors present in the observational
research that showed an association between abacavir therapy and the relative
risk of heart attack.
Patients were followed for a median of three years. They
were relatively young (77% under 45), predominately male (82%) and racially
diverse. HIV treatment outcomes were good. The patients had an undetectable
viral load for 83% of total follow-up time and a CD4 cell count above 350
cells/mm3 for 63% of the study period.
Overall, 34% of patients initiated a combination that
included abacavir, 9% started therapy with ddI (didadosine, Videx, which has also been linked with
an increase in the relative risk of heart attack), and 21% were treated with an
initial regimen that included tenofovir (Viread,
also in the combination pills Truvada
and Atripla).
During 17,404 person years of follow-up a total of 36 heart
attacks were recorded.
Overall incidence was 2.1 per 100 person years, “demonstrating
a low absolute risk of MI in this typical cohort of individuals initiating
ART.”
A total of twelve heart attacks were observed in the first
year of therapy, and an additional 24 in the next five years.
One-year incidence of heart attack for patients taking
abacavir was 1.9 per 100 person years, compared to an incidence of 2.9 per 100
person years for patients taking non-abacavir regimens. The six-year heart
attack incidences were 1.5 vs. 2.3 per 100 person years respectively for
abacavir and non-abacavir regimens.
None of the investigators’ statistical analyses showed a
relationship between abacavir and an increased risk of heart attack. This was
also the case when the researchers extended their scope to include other
serious cardiovascular events.
Factors associated with heart attack risk were older age
(short-term, p = 0.008; long-term, p < 0.001), a pre-therapy history of two
or more established risk factors for cardiovascular disease (short term, p =
0.005; long term, p < 0.001), and smoking (short-term, not significant: long
term, p = 0.05).
“Over a period of up to 6 years from ART initiation, we
observed a very low absolute risk of MI and other CVD events,” comment the
investigators, who continue, “we found no evidence of an increased risk of MI
or serious CVD associated with the use of abacavir as part of initial treatment
over the first year of ART and longer term that was consistent in as-treated
and sensitivity analyses.”
They therefore conclude, “classic CVD risk factors were the
strongest predictors of MI and other serious CVD events and should be the main
focus in assessing CVD risk among HIV-1 infected individuals.”