FDA: Two HIV drugs may be linked with increased coronary risk

April 2008

The FDA is conducting an ongoing safety review of the potential for increased risk of myocardial infarction associated with two nucleoside reverse transcriptase inhibitor HIV drugs, officials said in a March 27 FDA statement.

The medications under review are abacavir (Ziagen, GlaxoSmithKline) and didanosine (Videx, Bristol-Myers Squibb).

In a large, multisite study, researchers found the risk of myocardial infarction was increased by 49% in patients taking didanosine and 90% in patients taking abacavir.

Risk did not increase over time and appeared to be reversible after abacavir or didanosine use was stopped. The effect was not seen six months after drug use ceased.

D:A:D data used

Analyses of data collected through Feb. 1, 2007 examined risk of myocardial infarction in patients taking selected NRTIs. The review is the result of findings from the Data Collection on Adverse Events in Anti-HIV Drugs (D:A:D) study. D:A:D is a large observational study of HIV patients (n=33,347) living in North America, Europe and Australia. Patients in the study are being followed to evaluate both short- and long-term adverse effects from HIV drugs.

GlaxoSmithKline officials received preliminary findings from the study in late 2007 and conducted its own search of its clinical study databases. Results were inconclusive, but did not show increased risk for myocardial infarction. Bristol Myers Squibb officials noted similar results for its drug, didanosine; they also noted clinical trial results were inconclusive.

Relative risk for myocardial infarction were described for patients who have cumulatively used the medication, those who have recently used the medication, and those who used the drug in the past, which researchers defined as greater than six months prior to the study.

The D:A:D researchers noted a greater risk for myocardial infarction in patients taking NRTIs who had other risk factors for heart disease. Risk factors included a history of heart disease, high cholesterol, high blood pressure, diabetes, smoking and age.

FDA officials said they believe the D:A:D study analyses may be incomplete. No analyses were conducted evaluating the risk for myocardial infarction in patients taking two other NRTIs, tenofovir (Viread, Gilead) or emtricitabine (Emtriva, Gilead). FDA officials continue to evaluate the risks and benefits of abacavir and didanosine.

This evaluation may result in revised product labeling, FDA officials said in a statement. Until the evaluation is complete, health care providers should evaluate potential risks and benefits of every antiretroviral in a patient regimen, including abacavir and didanosine.