Statins Ineffectual in Lupus

Daily atorvastatin use had no significant impact on atherosclerosis progression among systemic lupus erythematosus patients, compared with placebo.

Indeed, among SLE patients without hyperlipidemia, nonstatin interventions "should be considered for the accelerated atherosclerosis of SLE," noted Dr. Michelle Petri, professor of medicine and director of the lupus center at Johns Hopkins University, Baltimore, in the May issue of the Annals of the Rheumatic Diseases.

Dr. Petri and colleagues looked at 200 patients with SLE. To be included in the analysis, patients could not have a history of atherosclerotic events, chronic liver disease, or statin use in the 3 months prior to the study. Patients were also excluded if they had baseline triglyceride levels greater than 500 mg/dL, levels of LDL cholesterol greater than 190 mg/dL, creatinine kinase levels greater than 1.5 times the upper limit of normal, or liver-function test findings greater than two times the upper limit of normal (Ann. Rheum. Dis. 2011;70:760-5).

Patients’ mean age was 48 years, and 92% were female. Roughly two-thirds of patients were white, and the remaining one-third were black.

Patients were randomized to receive either 40 mg daily of atorvastatin or an identical placebo; they underwent helical CT scans and carotid duplex scans at baseline and 2 years.

At baseline, the mean total cholesterol was 186 mg/dL, and 34% of patients had total cholesterol levels greater than 200 mg/dL. The mean LDL cholesterol was 103 mg/dL, with 48% having LDL levels in excess of 100 mg/dL.

Also at baseline, 57% of participants had no coronary artery calcium; 22% had an Agatston score of 0-10; 12% scored 11-99; and 8% scored 100 or greater. The carotid intima-media thickness (IMT) was 0.4-0.5 mm in 23% of patients, 0.5-0.6 mm in 46%, 0.6-0.7 mm in 19%, and 0.7-1.0 mm in 12%.

Overall, 17% of patients had carotid plaque at baseline.

According to Dr. Petri, by 2 years there were no statistically significant differences between groups with respect to changes in coronary artery calcium score or carotid IMT. Both groups did have a statistically significant change in carotid IMT by 2 years (0.07 mm between baseline and study end for the treatment group vs. 0.09 mm for the placebo group; P less than 0.0001 for both groups) but this was not significant between groups.

Overall, among the patients treated with statin, 48% showed improved carotid IMT (defined as better than 10% change); 6% stayed the same, and 46% got worse. Among the placebo group, 29% of patients improved, whereas 4% remained the same and 67% of patients had worse measurements after 2 years.

The difference between patients who improved was a statistically significant difference (P = .014).

Among statin patients who had no carotid plaque at baseline, 25% were found to have plaque at 2 years, compared with 23% among placebo patients (P = .77).

Looking at laboratory values, the only significant difference between groups was seen in levels of total cholesterol. Among atorvastatin patients, this measure dropped more than 30 points over the study period, from 181.6 mg/dL to 150.7 mg/dL; for placebo patients, it rose 5.5 points, from 190.1 mg/dL to 195.6 mg/dL (P less than 0.0001).

Meanwhile, 51% in the atorvastatin group had abnormal ALT levels during follow-up, compared with 31% in the placebo group (P = .01); creatine kinase values did not differ between groups.

The authors conceded that 2 years of follow-up may not have been sufficient to observe any benefit in SLE; they added that an 80-mg dose (vs. the 40 mg used in this study) may have proved more efficacious. However, "it would not have been possible for us to have done our study with 80 mg, given the high frequency" of abnormal liver function tests with 40-mg atorvastatin, they wrote.

"Although statins may have some benefit for the disease activity of rheumatoid arthritis or multiple sclerosis, we found no evidence of a beneficial effect on SLE activity," concluded the authors.

Nevertheless, "patients with SLE with hyperlipidemia ... should continue to be treated with statins and other antihyperlipidemic medications if they meet the National Cholesterol Education Program guideline thresholds for treatment," they added.

Dr. Petri disclosed being a former member of the Pfizer advisory board and participating in a Pfizer speakers bureau unrelated to atorvastatin. Pfizer is the maker of atorvastatin, marketed as Lipitor.

None of the other authors had any other competing interests to disclose.

Daily atorvastatin use had no significant impact on atherosclerosis progression among systemic lupus erythematosus patients, compared with placebo.

Indeed, among SLE patients without hyperlipidemia, nonstatin interventions "should be considered for the accelerated atherosclerosis of SLE," noted Dr. Michelle Petri, professor of medicine and director of the lupus center at Johns Hopkins University, Baltimore, in the May issue of the Annals of the Rheumatic Diseases.

Dr. Petri and colleagues looked at 200 patients with SLE. To be included in the analysis, patients could not have a history of atherosclerotic events, chronic liver disease, or statin use in the 3 months prior to the study. Patients were also excluded if they had baseline triglyceride levels greater than 500 mg/dL, levels of LDL cholesterol greater than 190 mg/dL, creatinine kinase levels greater than 1.5 times the upper limit of normal, or liver-function test findings greater than two times the upper limit of normal (Ann. Rheum. Dis. 2011;70:760-5).

Patients’ mean age was 48 years, and 92% were female. Roughly two-thirds of patients were white, and the remaining one-third were black.

Patients were randomized to receive either 40 mg daily of atorvastatin or an identical placebo; they underwent helical CT scans and carotid duplex scans at baseline and 2 years.

At baseline, the mean total cholesterol was 186 mg/dL, and 34% of patients had total cholesterol levels greater than 200 mg/dL. The mean LDL cholesterol was 103 mg/dL, with 48% having LDL levels in excess of 100 mg/dL.

Also at baseline, 57% of participants had no coronary artery calcium; 22% had an Agatston score of 0-10; 12% scored 11-99; and 8% scored 100 or greater. The carotid intima-media thickness (IMT) was 0.4-0.5 mm in 23% of patients, 0.5-0.6 mm in 46%, 0.6-0.7 mm in 19%, and 0.7-1.0 mm in 12%.

Overall, 17% of patients had carotid plaque at baseline.

According to Dr. Petri, by 2 years there were no statistically significant differences between groups with respect to changes in coronary artery calcium score or carotid IMT. Both groups did have a statistically significant change in carotid IMT by 2 years (0.07 mm between baseline and study end for the treatment group vs. 0.09 mm for the placebo group; P less than 0.0001 for both groups) but this was not significant between groups.

Overall, among the patients treated with statin, 48% showed improved carotid IMT (defined as better than 10% change); 6% stayed the same, and 46% got worse. Among the placebo group, 29% of patients improved, whereas 4% remained the same and 67% of patients had worse measurements after 2 years.

The difference between patients who improved was a statistically significant difference (P = .014).

Among statin patients who had no carotid plaque at baseline, 25% were found to have plaque at 2 years, compared with 23% among placebo patients (P = .77).

Looking at laboratory values, the only significant difference between groups was seen in levels of total cholesterol. Among atorvastatin patients, this measure dropped more than 30 points over the study period, from 181.6 mg/dL to 150.7 mg/dL; for placebo patients, it rose 5.5 points, from 190.1 mg/dL to 195.6 mg/dL (P less than 0.0001).

Meanwhile, 51% in the atorvastatin group had abnormal ALT levels during follow-up, compared with 31% in the placebo group (P = .01); creatine kinase values did not differ between groups.

The authors conceded that 2 years of follow-up may not have been sufficient to observe any benefit in SLE; they added that an 80-mg dose (vs. the 40 mg used in this study) may have proved more efficacious. However, "it would not have been possible for us to have done our study with 80 mg, given the high frequency" of abnormal liver function tests with 40-mg atorvastatin, they wrote.

"Although statins may have some benefit for the disease activity of rheumatoid arthritis or multiple sclerosis, we found no evidence of a beneficial effect on SLE activity," concluded the authors.

Nevertheless, "patients with SLE with hyperlipidemia ... should continue to be treated with statins and other antihyperlipidemic medications if they meet the National Cholesterol Education Program guideline thresholds for treatment," they added.

Dr. Petri disclosed being a former member of the Pfizer advisory board and participating in a Pfizer speakers bureau unrelated to atorvastatin. Pfizer is the maker of atorvastatin, marketed as Lipitor.

None of the other authors had any other competing interests to disclose.

Daily atorvastatin use had no significant impact on atherosclerosis progression among systemic lupus erythematosus patients, compared with placebo.

Indeed, among SLE patients without hyperlipidemia, nonstatin interventions "should be considered for the accelerated atherosclerosis of SLE," noted Dr. Michelle Petri, professor of medicine and director of the lupus center at Johns Hopkins University, Baltimore, in the May issue of the Annals of the Rheumatic Diseases.

Dr. Petri and colleagues looked at 200 patients with SLE. To be included in the analysis, patients could not have a history of atherosclerotic events, chronic liver disease, or statin use in the 3 months prior to the study. Patients were also excluded if they had baseline triglyceride levels greater than 500 mg/dL, levels of LDL cholesterol greater than 190 mg/dL, creatinine kinase levels greater than 1.5 times the upper limit of normal, or liver-function test findings greater than two times the upper limit of normal (Ann. Rheum. Dis. 2011;70:760-5).

Patients’ mean age was 48 years, and 92% were female. Roughly two-thirds of patients were white, and the remaining one-third were black.

Patients were randomized to receive either 40 mg daily of atorvastatin or an identical placebo; they underwent helical CT scans and carotid duplex scans at baseline and 2 years.

At baseline, the mean total cholesterol was 186 mg/dL, and 34% of patients had total cholesterol levels greater than 200 mg/dL. The mean LDL cholesterol was 103 mg/dL, with 48% having LDL levels in excess of 100 mg/dL.

Also at baseline, 57% of participants had no coronary artery calcium; 22% had an Agatston score of 0-10; 12% scored 11-99; and 8% scored 100 or greater. The carotid intima-media thickness (IMT) was 0.4-0.5 mm in 23% of patients, 0.5-0.6 mm in 46%, 0.6-0.7 mm in 19%, and 0.7-1.0 mm in 12%.

Overall, 17% of patients had carotid plaque at baseline.

According to Dr. Petri, by 2 years there were no statistically significant differences between groups with respect to changes in coronary artery calcium score or carotid IMT. Both groups did have a statistically significant change in carotid IMT by 2 years (0.07 mm between baseline and study end for the treatment group vs. 0.09 mm for the placebo group; P less than 0.0001 for both groups) but this was not significant between groups.

Overall, among the patients treated with statin, 48% showed improved carotid IMT (defined as better than 10% change); 6% stayed the same, and 46% got worse. Among the placebo group, 29% of patients improved, whereas 4% remained the same and 67% of patients had worse measurements after 2 years.

The difference between patients who improved was a statistically significant difference (P = .014).

Among statin patients who had no carotid plaque at baseline, 25% were found to have plaque at 2 years, compared with 23% among placebo patients (P = .77).

Looking at laboratory values, the only significant difference between groups was seen in levels of total cholesterol. Among atorvastatin patients, this measure dropped more than 30 points over the study period, from 181.6 mg/dL to 150.7 mg/dL; for placebo patients, it rose 5.5 points, from 190.1 mg/dL to 195.6 mg/dL (P less than 0.0001).

Meanwhile, 51% in the atorvastatin group had abnormal ALT levels during follow-up, compared with 31% in the placebo group (P = .01); creatine kinase values did not differ between groups.

The authors conceded that 2 years of follow-up may not have been sufficient to observe any benefit in SLE; they added that an 80-mg dose (vs. the 40 mg used in this study) may have proved more efficacious. However, "it would not have been possible for us to have done our study with 80 mg, given the high frequency" of abnormal liver function tests with 40-mg atorvastatin, they wrote.

"Although statins may have some benefit for the disease activity of rheumatoid arthritis or multiple sclerosis, we found no evidence of a beneficial effect on SLE activity," concluded the authors.

Nevertheless, "patients with SLE with hyperlipidemia ... should continue to be treated with statins and other antihyperlipidemic medications if they meet the National Cholesterol Education Program guideline thresholds for treatment," they added.

Dr. Petri disclosed being a former member of the Pfizer advisory board and participating in a Pfizer speakers bureau unrelated to atorvastatin. Pfizer is the maker of atorvastatin, marketed as Lipitor.

None of the other authors had any other competing interests to disclose.