GlaxoSmithKline statement - Lancet publication of D:A:D data

GlaxoSmithKline statement - Lancet publication of D:A:D data

GSK data show no increased risk of myocardial infarction associated with abacavir

Issued:  Wednesday 2 April 2008

Data published in the Lancet today from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) suggest a possible association between anti-retroviral therapy (ART) regimens that contain abacavir and an increased risk of myocardial infarction.  Conversely, analyses of GlaxoSmithKline data show no increased risk of myocardial infarction associated with abacavir.

"The D:A:D findings are unexpected, since we have not seen similar findings in our studies, and we are unaware of any potential biological mechanism that would explain them.  In our own analysis of trials involving more than 9,600 patients, no increased risk of heart attack associated with abacavir was found. It is important to note that although the relative risk of heart attack risk seen in the D:A:D study was increased in patients who had recently taken abacavir, the likelihood of an individual patient having a heart attack remains low in absolute terms. Abacavir remains an important treatment option for patients with HIV and patients should not discontinue treatment on their own," said Didier Lapierre, Vice President of Clinical Development for Infectious Diseases at GlaxoSmithKline.

GSK data

GSK has analysed the company’s internal databases, which include information from external post marketing surveillance reports and data from 54 clinical trials with more than 14,000 patients, over 9,600 of whom were on abacavir. The analysis of GSK data shows no increased risk of myocardial infarction associated with abacavir.  In addition, GSK is not aware of any confirmed increased risk of myocardial infarction with abacavir in the published literature.

No biological mechanism linking abacavir treatment with myocardial infarction has so far been identified.  GSK believes that in totality, the data on the association of myocardial infarction with abacavir treatment are inconclusive at this time.

In recent years, GSK has increased the focus of our HIV research efforts, including initiating studies that identify and analyse risk factors and potential drug toxicities.  GSK regards this as a critical part of establishing and maintaining drug safety and several studies have been performed and others are ongoing focusing on the long term safety impact of abacavir.

D:A:D database findings

Accumulated observational data were sufficient for the D:A:D to analyse five commonly used nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, stavudine, lamivudine and abacavir.  No analyses were conducted evaluating the risk of myocardial infarction among patients taking tenofovir or emtricitabine, two other drugs in the class of NRTIs

Overall, the data cited by the D:A:D are uncommon events: 6.1 events/1000 patient years among patients who had taken abacavir in the last 6 months versus 2.6 events/1000 patient years for those who had not (a difference of 3.5 events per 1000 patient years). By comparison to this doubling of relative risk, smoking can increase a person’s risk of heart attack by two or three times, while high cholesterol can increase the risk of heart attack further.   As the D:A:D position paper states, for patients who smoke: ”…stopping smoking would do more to reduce the risk of having a heart attack and other serious diseases more than by stopping abacavir:”

Observational studies can provide important information given their size and scope, but because they analyse patient experience in a real-life setting, they are subject to more variables than scientifically controlled clinical trials.  It is important that findings of observational studies are confirmed with other data, and that reasons for any potential link between drug and effect be identified.

Regulatory status

Importantly, on March 27, 2008, the US Federal Drugs Administration (FDA) stated that they currently believe the analyses conducted by the D:A:D are incomplete.  They also indicate that the results of the GSK analysis are inconclusive, but did not show an increased risk.  They are considering, but have not concluded, whether any regulatory action is warranted. In addition, the FDA stressed the risks of switching patients’ treatment without proper individual assessment, urging caution. The EMEA is also reviewing the D:A:D data and will post their findings in the near future.

Implications for managing HIV

HIV is a serious, life-threatening disease, and a number of factors go into choosing the right therapy.  Therefore, GSK believes that:

-    Patients should NOT discontinue treatment on their own.

-    Although the D:A:D study data suggest a relative risk increase in heart attack risk associated with abacavir, that risk remains low in absolute terms, and therefore abacavir remains an important treatment option for those patients.

-    The total patient profile including comorbidities, concomitant medications, previous retroviral experience, as well as the underlying risk of coronary heart disease should be considered when prescribing HIV antiretroviral therapy, including abacavir. Action should be taken to minimize modifiable cardiovascular risk factors in all patients (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking) in line with current guidelines.

About HAART theory

Highly Active Anti-Retroviral Therapy (HAART) has revolutionized HIV treatment and dramatically extended the lifespan of HIV patients.  The NRTI class, including abacavir, remains a cornerstone of HIV therapy; approximately 25% of HIV patients on HAART take abacavir as a proven medicine effective in treating HIV.  For patients who have failed previous therapy, abacavir may be an essential part of treatment.

As with all medicines, doctors and patients must weigh the risks of the disease against the risks and benefits of the medicines available to treat it.  Certain risks may be able to be managed as part of standard HIV patient care.

About GlaxoSmithKline

GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com [1].