Vancouver researchers urge caution with combinations of lipid drugs

6 November 2004. Related: Side effects, Lipodystrophy and metabolic complications.

Sean R. Hosein, catie.org

As people age there is a trend to gradually develop abnormal levels of sugar and lipids (cholesterol, triglycerides) in their blood.

People with HIV/AIDS (PHAs) who use highly active antiretroviral therapy (HAART) can also develop high levels of these substances. If left untreated, this increases the risk of developing diabetes and cardiovascular disease.

Sometimes a combination of changes to diet and lifestyle (such as exercising and quitting smoking) can help improve blood sugar and cholesterol levels. However, for some HAART users, these changes to diet and lifestyle may not be enough. In such cases, doctors may prescribe drugs, including the following:

• Fibrates: These drugs help lower triglycerides and raise levels of good cholesterol (HDL-c). Examples of fibrates include fenofibrate (Lipidil, Tricor) and gemfibrozil (Lopid).
• Glitazones: These drugs can make cells more sensitive to the effects of the hormone insulin, helping to reduce high sugar levels in the blood. Glitazones can also raise levels of good cholesterol. Examples of glitazones include pioglitazone (Actos) and rosiglitazone (Avandia).

Because increased lipid levels may also be associated with higher-than-normal blood sugar, sometimes doctors prescribe both fibrates and glitazones. In theory, a combination of both drugs should maintain or even enhance the decrease in triglycerides seen with either drug alone.

A team of researchers in Vancouver, British Columbia, from the Canadian HIV Trials Network, the Centre for Excellence in HIV/AIDS, and the Healthy Heart Programme at St Paul’s Hospital recently reported an unexpected result with combinations of both classes of drugs. They found that HDL-c levels decreased significantly in both HIV positive (33%) and HIV negative (20%) people. Moreover, among HIV positive people, triglycerides rose on average by almost 50% in those taking combination therapy with lipid drugs.

Study details

Researchers reviewed the medical records of three groups of people:

* Group A: PHAs taking fenofibrate – 12 participants

* Group B: PHAs taking fenofibrate and rosiglitazone – 9 participants

* Group C: HIV negative diabetics taking fenofibrate and rosiglitazone – 12 participants

The profile of PHAs at the start of the study were: 1 female, 20 males; average age – 50 years; most had been taking the study drugs for between six and seven months; and PHAs did not change their HAART regimens while the study took place

Results

Changes in HDL-cholesterol levels were +19%, -33% and –20% in Groups A, B and C respectively. These differences were statistically significant.

Changes in triglyceride levels were – 27%, + 48% and – 9% in Groups A, B and C respectively.

When participants on combination lipid therapy stopped taking either drug, HDL-c concentrations rose to pre-study levels.

Note that PHAs taking fenofibrate alone (group A) had the expected increase in HDL-c and decrease in triglycerides.

The research team is not certain why HDL-c levels fell with combination lipid therapy, and they think an interaction between the two drugs is not likely. They hope that their report will stimulate other researchers to study the issue and find an explanation. Until this happens, the Vancouver researchers suggest that the combinations of fenofibrate and rosiglitazone be used with caution.

References:

1. Normen L, Frohlich J, Montaner J, et al. Combination therapy with fenofibrate and rosiglitazone paradoxically lowers serum HDL cholesterol. Diabetes Care 2004;27(9):2241-2242.
2. Davidson MH and Toth PP. Combination therapy in the management of complex dyslipidaemias. Current Opinion in Lipidology 2004;15:423-243.

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