Large study shows that abacavir doesn't increase short or long-term risk of heart attack

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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.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

absolute risk

The chance that a person will experience a specific event during a period of time. It is always between 0 and 1 (when expressed as a probability), or between 0 and 100 (when expressed as a percentage).

cardiovascular

Relating to the heart and blood vessels.

relative risk

Comparing one group with another, expresses differences in the risk of something happening. For example, in comparison with group A, people in group B have a relative risk of 3 of being ill (they are three times as likely to get ill). A relative risk above 1 means the risk is higher in the group of interest; a relative risk below 1 means the risk is lower. 

sensitivity analysis

An additional analysis of data, also known as a “what–if” analysis, which indicates how robust the study’s results are. Specific assumptions or variables may be changed, to estimate the outcome in a range of scenarios.

 “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.”

References

Ribaudo HJ et al. No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT. Clin Infect Dis 52: 929-40, 2011 (click here for access to the free article).