Danes find more evidence linking abacavir treatment with increased risk of heart attack

Michael Carter
Published: 02 February 2010

Researchers have found further evidence suggesting that treatment with abacavir increases the risk of heart attack. In a study published in the February edition of HIV Medicine investigators from Denmark report that patients who took the drug doubled their risk of heart attack.

Further analysis that took into account potentially confounding factors did not substantially affect this finding.

Recently published results from the D:A:D study showed that patients taking abacavir (Ziagen, also in the combination pills Kivexa and Trizivir) had a 70% increase in their relative risk of heart attack. An association between therapy with the drug and heart attack was also found in the SMART treatment interruption study.

Investigators from Denmark wished to determine the impact of abacavir therapy and the risk of hospitalisation because of heart attack.

A total of 2930 HIV-positive patients in Denmark were included in the study. Information on the incidence of heart attack amongst these individuals up to May 2007 was obtained by the investigators.

The researchers noted, “this nonrandomised cohort study may be subject to the same confounders as those potentially affecting the D:A:D study. For this reason, we used several approaches to control for confounding”.

Therefore, in addition to obtaining data on the use of abacavir and other anti-HIV drugs, the investigators also gathered information on other factors potentially linked to a risk of heart attack. These included age, gender, blood lipid levels, blood pressure, the presence of lung, liver or kidney disease, age, duration of HIV infection, CD4 cell count at the time antiretroviral therapy was started, race, injecting drug use and alcoholism.

The association between treatment with abacavir and heart attack was then examined in four separate sets of statistical analyses.

Of the 2930 individuals in the cohort, 1761 were treated with abacavir. A little over a third of these patients started HIV treatment with a regimen that included abacavir, the remaining 66% of individuals switching to the drug at least two years after initiating antiretroviral therapy.

The abacavir-treated patients contributed 19,124 person years of follow-up.

A total of 67 heart attacks were observed. Of these 36 occurred after treatment with abacavir was started.

The overall hospitalisation rate for heart attack was 3.5 per 1000 person years of follow-up.

Before initiating therapy with abacavir, the heart attack-related hospitalisation rate was 2.4 per 1000 person years.

However, after starting treatment with abacavir this rate of hospitalisation leapt to 5.7 per 1000 person years.

The investigators’ unadjusted analysis showed that the relative risk associated with treatment with abacavir and heart attack was 2.22 (95% CI, 1.31-3.76). This was essentially unaltered in two further sets of analyses that took into account potentially confounding factors (adjusted relative risk [ARR]: 2.00; 95% CI, 1.10-1.94; and in a 'propensity score model', ARR: 2.00; 95% CI, 1.07-3.76).

Heart attack risk was increased by 95% during therapy with abacavir (ARR: 1.95; 95% CI, 1.05-3.60; propensity score model, ARR: 1.95; 95% CI, 1.01-3.72).

However, there was also evidence that this increased risk of heart attack persisted after therapy with the drug was stopped (ARR: 2.37; 95% CI, 0.88-6.36; propensity score model, ARR: 2.37; 95% CI, 0.82-6.85).

Some investigators and clinicians have suggested that abacavir’s association with heart attack could be the result of a so-called “channelling bias”. This involves patients with pre-existing risk factors for heart attack, for example lipodystrophy or poor adherence, being offered or switched to abacavir because of its benefits for patients with these characteristics.

However, the Danish research did not support this theory. They found that the heart attack risks were similar for patients starting antiretroviral therapy with abacavir or switching to treatment with the drug.

“We confirmed the finding of the D:A:D study of an increased risk of myocardial infarction [heart attack] after initiation of abacavir therapy”, comment the investigators.

“In conclusion”, write the investigators, “the findings of this study…suggest that abacavir is associated with an increased risk of myocardial infarction. Further studies are needed to quantify the association and to control for any potential, as yet unmeasured, confounding.”

Reference

Obel N et al. Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIV Medicine, 11: 130-36, 2010.

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