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Attacking LDL Cholesterol in People on ARVs Has Mixed Results
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5th IAS Conference on HIV Pathogenesis,
Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Aggressively attacking dangerous low-density lipoprotein (LDL) cholesterol in antiretroviral-treated people lowered LDL cholesterol more than a standard intervention [1]. But compared with standard care, the multipronged approach in this small randomized trial had no greater impact on the primary endpoint--carotid artery intima media thickness after 12 months--or on markers of inflammation.
Researchers at two Spanish clinics enrolled 68 people with well-controlled viral replication on a stable antiretroviral regimen and with two or more cardiovascular risk factors or a Framingham risk score at or above 10%.
The multifaceted intensive intervention--aimed at getting LDL cholesterol below 100 mg/dL-started with atorvastatin escalated from 10 to 20 mg, then added 10 mg of ezetimibe if high-dose atorvastatin did not achieve the LDL goal. People in the intensive intervention arm got antiplatelet therapy (usually aspirin) and switched other protease inhibitors (PIs) to boosted or unboosted atazanavir. Investigators also "strongly" encouraged these people to give up smoking and tried to help them reach internationally defined blood pressure and blood glucose goals. The standard intervention aimed at pushing LDL cholesterol below 130 mg/dL without specifying strategies.
The investigators randomized 32 people to the intensive intervention and 36 to standard care. Three people in the intensive group and 2 in the standard-of-care group stopped returning for study visits, so the analysis involved 29 and 34 people in the two groups.
When the study began, about 40% in each group were taking a PI, and there were no major antiretroviral differences between arms. About two thirds in each group had abnormal lipids, and about 20% smoked. Median age was higher in the intensive group (53.7 versus 47.8), but that difference did not reach statistical significance. Almost all study participants were men. Eleven people in the intensive group (38%) and 18 in the standard group (50%) had evidence of carotid plaques, a nonsignificant difference.
After 12 months, median change in carotid intima media thickness (a cardiovascular disease predictor and the primary endpoint) measured +1.63% in the intensive group and +1.79% in the control group, a nonsignificant difference (P = 0.59).
People assigned to the intensive regimen did reap greater reductions in LDL cholesterol, cutting median levels from 141 to 87.5 mg/dL compared with a drop from 131 to 126 mg/dL in the standard-of-care group. Seventeen people in the intensive group (59%) reached the LDL target of less than 100 mg/dL. Median total cholesterol was also significantly lower in the intensive group at week 48, but triglycerides were not. Median Framingham score slipped from 16% to 14.5% in the intensive group (P < 0.05) and from 14% to 12% in the standard-of-care group (nonsignificant).
Intensive management had no significant impact on three standard markers of inflammation-high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor alpha.
No virologic failures occurred during the trial, and no one had serious treatment side effects or lab abnormalities; these variables did not differ significantly between treatment arms.
The investigators noted several study limitations, including the small size (with 70% power to detect a 15% difference between arms) and the relatively short follow-up. They have already monitored these people for 3 years and are analyzing those results. Session cochair Esteban Martinez (University of Barcelona) noted that the study does establish that antiretroviral-treated people can safely tolerate such a regimen. Whether following this plan and getting LDL under 100 mg/dL yields clinical benefits remains undetermined.
Reference
1. Masia M, Bernal E, Padilla S, et al. A randomized trial comparing an intensive versus a standard intervention in stable HIV-infected patients with moderate-high cardiovascular risk. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract TUAB201.
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