Statin Didn't Lessen Atherosclerosis in Lupus

Atorvastatin therapy did not improve subclinical measures of atherosclerosis or disease activity, compared with placebo, in a 2-year, randomized, double-blind study of 200 adults with systemic lupus erythematosus published in Annals of the Rheumatic Diseases.

The results surprised the investigators because atorvastatin had seemed to be an ideal choice to interrupt the accelerated atherosclerosis seen in SLE, reported Dr. Michelle A. Petri.

Previous studies had shown some potential benefits from the anti-inflammatory effects of statins in other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Findings from one small study of pravastatin in patients with SLE found that it reduced total cholesterol and LDL cholesterol levels but did not reduce C-reactive protein levels.

In the current study, there was no significant difference between patients who were randomized to 40 mg/day atorvastatin or placebo in progression of coronary artery calcium, carotid intima media thickness, or carotid plaque. There also were no significant differences between groups in measures of disease activity, inflammation, or endothelial cell activation, reported Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore, and her associates (Ann. Rheum. Dis. 2011 Dec. 21 [doi:10.1136/ard.2010.136762]).

The atorvastatin group, however, was more likely to develop elevations in liver function tests, even as late as 18 months into the study.

The lack of any evidence of an anti-inflammatory benefit from the statin suggests that something besides statins should be considered to manage the accelerated atherosclerosis of SLE, the investigators suggested. Patients with SLE and hyperlipidemia should continue to be treated with statins and other lipid-lowering medications, they added, but with closer monitoring of liver function tests even if the statin dosage doesn’t change, reported Dr. Petri, who is also the director of lupus center at Johns Hopkins as well as director of the Hopkins Lupus Cohort.

At the start of the study, the groups were similar and none of the patients had taken statins for at least 3 months. They underwent helical CT scanning to assess coronary artery calcium and carotid duplex to assess carotid intima media thickness and carotid plaque. These tests were repeated at the 2-year follow-up. Records of disease activity in the 2 years prior to starting the study were compared with quarterly measures of disease activity during the study.

In all, 96 patients on atorvastatin and 91 on placebo completed the study.

At baseline, 42% of patients in the atorvastatin group and 43% in the placebo group had coronary artery calcium. Carotid plaque was seen in 20% of the atorvastatin group and 15% of the placebo group, a difference that was not statistically significant.

Coronary artery calcium scores changed in 51% of those on atorvastatin and in 54% of those on placebo, with no significant differences between groups in the proportions whose scores increased or decreased, or by how much. All patients with carotid plaque at baseline also had it at follow-up. Among patients without carotid plaque at baseline, 25% in the atorvastatin group and 23% on placebo progressed to having plaque at follow-up.

The mean carotid intima media thickness was 0.59 mm in the atorvastatin group and 0.57 mm in the placebo group at baseline, and 0.66 mm in both groups after 2 years. In a post hoc analysis of the proportions of patients in whom carotid intima media thickness improved, stayed the same, or got worse, results favored atorvastatin, the investigators noted.

Changes in levels of total cholesterol and lipoprotein differed significantly between groups. In the atorvastatin group, total cholesterol decreased by 31 mg/dL (or 17%), compared with an increase in the placebo group of 6 mg/dL (or 3%). In the atorvastatin group, lipoprotein levels increased by 8 mg/dL (or 12%), compared with a decrease in the placebo group of 7 mg/dL (or 10%).

Disease activity was measured using the Safety of Estrogens in Lupus: National Assessment revision of the SLE Disease Activity Index.

Dr. Petri was formerly an advisor and speaker for Pfizer, which markets atorvastatin. None of her coauthors had conflicts of interest. The study was funded by the Alliance for Lupus Research, the Arthritis Foundation, the Hopkins Lupus Cohort, and the National Center for Research Resources.

Atorvastatin therapy did not improve subclinical measures of atherosclerosis or disease activity, compared with placebo, in a 2-year, randomized, double-blind study of 200 adults with systemic lupus erythematosus published in Annals of the Rheumatic Diseases.

The results surprised the investigators because atorvastatin had seemed to be an ideal choice to interrupt the accelerated atherosclerosis seen in SLE, reported Dr. Michelle A. Petri.

Previous studies had shown some potential benefits from the anti-inflammatory effects of statins in other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Findings from one small study of pravastatin in patients with SLE found that it reduced total cholesterol and LDL cholesterol levels but did not reduce C-reactive protein levels.

In the current study, there was no significant difference between patients who were randomized to 40 mg/day atorvastatin or placebo in progression of coronary artery calcium, carotid intima media thickness, or carotid plaque. There also were no significant differences between groups in measures of disease activity, inflammation, or endothelial cell activation, reported Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore, and her associates (Ann. Rheum. Dis. 2011 Dec. 21 [doi:10.1136/ard.2010.136762]).

The atorvastatin group, however, was more likely to develop elevations in liver function tests, even as late as 18 months into the study.

The lack of any evidence of an anti-inflammatory benefit from the statin suggests that something besides statins should be considered to manage the accelerated atherosclerosis of SLE, the investigators suggested. Patients with SLE and hyperlipidemia should continue to be treated with statins and other lipid-lowering medications, they added, but with closer monitoring of liver function tests even if the statin dosage doesn’t change, reported Dr. Petri, who is also the director of lupus center at Johns Hopkins as well as director of the Hopkins Lupus Cohort.

At the start of the study, the groups were similar and none of the patients had taken statins for at least 3 months. They underwent helical CT scanning to assess coronary artery calcium and carotid duplex to assess carotid intima media thickness and carotid plaque. These tests were repeated at the 2-year follow-up. Records of disease activity in the 2 years prior to starting the study were compared with quarterly measures of disease activity during the study.

In all, 96 patients on atorvastatin and 91 on placebo completed the study.

At baseline, 42% of patients in the atorvastatin group and 43% in the placebo group had coronary artery calcium. Carotid plaque was seen in 20% of the atorvastatin group and 15% of the placebo group, a difference that was not statistically significant.

Coronary artery calcium scores changed in 51% of those on atorvastatin and in 54% of those on placebo, with no significant differences between groups in the proportions whose scores increased or decreased, or by how much. All patients with carotid plaque at baseline also had it at follow-up. Among patients without carotid plaque at baseline, 25% in the atorvastatin group and 23% on placebo progressed to having plaque at follow-up.

The mean carotid intima media thickness was 0.59 mm in the atorvastatin group and 0.57 mm in the placebo group at baseline, and 0.66 mm in both groups after 2 years. In a post hoc analysis of the proportions of patients in whom carotid intima media thickness improved, stayed the same, or got worse, results favored atorvastatin, the investigators noted.

Changes in levels of total cholesterol and lipoprotein differed significantly between groups. In the atorvastatin group, total cholesterol decreased by 31 mg/dL (or 17%), compared with an increase in the placebo group of 6 mg/dL (or 3%). In the atorvastatin group, lipoprotein levels increased by 8 mg/dL (or 12%), compared with a decrease in the placebo group of 7 mg/dL (or 10%).

Disease activity was measured using the Safety of Estrogens in Lupus: National Assessment revision of the SLE Disease Activity Index.

Dr. Petri was formerly an advisor and speaker for Pfizer, which markets atorvastatin. None of her coauthors had conflicts of interest. The study was funded by the Alliance for Lupus Research, the Arthritis Foundation, the Hopkins Lupus Cohort, and the National Center for Research Resources.

Atorvastatin therapy did not improve subclinical measures of atherosclerosis or disease activity, compared with placebo, in a 2-year, randomized, double-blind study of 200 adults with systemic lupus erythematosus published in Annals of the Rheumatic Diseases.

The results surprised the investigators because atorvastatin had seemed to be an ideal choice to interrupt the accelerated atherosclerosis seen in SLE, reported Dr. Michelle A. Petri.

Previous studies had shown some potential benefits from the anti-inflammatory effects of statins in other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Findings from one small study of pravastatin in patients with SLE found that it reduced total cholesterol and LDL cholesterol levels but did not reduce C-reactive protein levels.

In the current study, there was no significant difference between patients who were randomized to 40 mg/day atorvastatin or placebo in progression of coronary artery calcium, carotid intima media thickness, or carotid plaque. There also were no significant differences between groups in measures of disease activity, inflammation, or endothelial cell activation, reported Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore, and her associates (Ann. Rheum. Dis. 2011 Dec. 21 [doi:10.1136/ard.2010.136762]).

The atorvastatin group, however, was more likely to develop elevations in liver function tests, even as late as 18 months into the study.

The lack of any evidence of an anti-inflammatory benefit from the statin suggests that something besides statins should be considered to manage the accelerated atherosclerosis of SLE, the investigators suggested. Patients with SLE and hyperlipidemia should continue to be treated with statins and other lipid-lowering medications, they added, but with closer monitoring of liver function tests even if the statin dosage doesn’t change, reported Dr. Petri, who is also the director of lupus center at Johns Hopkins as well as director of the Hopkins Lupus Cohort.

At the start of the study, the groups were similar and none of the patients had taken statins for at least 3 months. They underwent helical CT scanning to assess coronary artery calcium and carotid duplex to assess carotid intima media thickness and carotid plaque. These tests were repeated at the 2-year follow-up. Records of disease activity in the 2 years prior to starting the study were compared with quarterly measures of disease activity during the study.

In all, 96 patients on atorvastatin and 91 on placebo completed the study.

At baseline, 42% of patients in the atorvastatin group and 43% in the placebo group had coronary artery calcium. Carotid plaque was seen in 20% of the atorvastatin group and 15% of the placebo group, a difference that was not statistically significant.

Coronary artery calcium scores changed in 51% of those on atorvastatin and in 54% of those on placebo, with no significant differences between groups in the proportions whose scores increased or decreased, or by how much. All patients with carotid plaque at baseline also had it at follow-up. Among patients without carotid plaque at baseline, 25% in the atorvastatin group and 23% on placebo progressed to having plaque at follow-up.

The mean carotid intima media thickness was 0.59 mm in the atorvastatin group and 0.57 mm in the placebo group at baseline, and 0.66 mm in both groups after 2 years. In a post hoc analysis of the proportions of patients in whom carotid intima media thickness improved, stayed the same, or got worse, results favored atorvastatin, the investigators noted.

Changes in levels of total cholesterol and lipoprotein differed significantly between groups. In the atorvastatin group, total cholesterol decreased by 31 mg/dL (or 17%), compared with an increase in the placebo group of 6 mg/dL (or 3%). In the atorvastatin group, lipoprotein levels increased by 8 mg/dL (or 12%), compared with a decrease in the placebo group of 7 mg/dL (or 10%).

Disease activity was measured using the Safety of Estrogens in Lupus: National Assessment revision of the SLE Disease Activity Index.

Dr. Petri was formerly an advisor and speaker for Pfizer, which markets atorvastatin. None of her coauthors had conflicts of interest. The study was funded by the Alliance for Lupus Research, the Arthritis Foundation, the Hopkins Lupus Cohort, and the National Center for Research Resources.