Elsevier

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Volume 80, Issue 3, May 2013, Pages 244-249
Joint Bone Spine

Review
Do all lupus patients need statins?

https://doi.org/10.1016/j.jbspin.2012.08.014Get rights and content

Abstract

Statin therapy decreases cardiovascular morbidity and mortality rates when used as either primary or secondary prevention. An immunomodulating effect of statins has been suggested. Incontrovertible evidence of accelerated atheroma has been obtained in patients with systemic lupus erythematosus (SLE). Routine statin therapy in SLE patients might therefore produce both cardiovascular and immunological benefits. However, routine statin therapy is inappropriate in SLE patients, the main reason being the absence of a vast interventional study done specifically in this population. An immunomodulating role for statins in SLE has not been convincingly established. The effect of statin therapy on markers for subclinical atheroma (intima-media thickness changes over time) is unclear, and there are no studies proving that statins are effective when used for primary or secondary cardiovascular prevention. Nevertheless, we believe that a serum lipid profile should be obtained once a year in all SLE patients. There is a sound rationale for classifying all SLE patients as being at high cardiovascular risk and those receiving secondary prevention as at very high risk. Consequently, the serum LDL-cholesterol level must be kept below 100 mg/dL and 70 mg/dL in these two populations, respectively. Statins are the only widely recommended drugs for achieving these treatment targets. Statin therapy requires specific monitoring precautions (transaminase levels) given the high prevalence of comorbidities and use of concomitant medications in SLE patients.

Section snippets

Mechanism of action of statins

Statins inhibit the enzyme HMG-CoA reductase, which catalyzes the transformation of HMG-CoA into mevalonate [5], thereby blocking the pathway for cholesterol synthesis from mevalonate. Another effect of HMG-CoA reductase inhibition is a decrease in isoprenylated proteins such as farnesyl, geranyl, and geranyl-generanyl, which play a key role in anchoring signaling proteins (Ras, Rho, and heterotrimeric G proteins) to the cell membrane. The result is a wide variety of intracellular effects that

Epidemiology

Sound evidence of excess cardiovascular morbidity and mortality in SLE patients has been obtained [10]. Urowitz et al. first drew attention to the cardiovascular complications seen in SLE, based on an analysis of causes of death in 81 patients [11]. They found two mortality peaks: one occurred within the first year and was related to SLE activity and adverse effects of immunosuppressive drugs, and the other occurred more than 5 years after the diagnosis and was due to atherosclerosis [11].

Statins and subclinical atheroma

As indicated above, no therapeutic trials have specifically evaluated whether statin therapy diminishes morbidity and mortality rates in SLE patients. However, this issue has been addressed by evaluations of statin effects on atheroma in animal models and on markers for subclinical atheroma.

Animal models

The potential of statin therapy for decreasing disease activity in SLE has been evaluated in both animal models and human patients. The results are somewhat conflicting. In murine models, intraperitoneal atorvastatin diminished renal disease severity, anti-DNA antibody titers, and Class II antigen expression on monocytes and lymphocytes, whereas the same drug given orally had no effect [50], [51]. Pravastatin failed to affect renal disease, survival, or SLE activity, despite a significant

Statins as inducers of systemic lupus erythematosus

Statins have been reported to induce lupus. Between 1996 and 2005, 10 cases of SLE and three of subacute cutaneous SLE induced by statin therapy were reported [56]. However, the causal relationship between statin exposure and lupus development remains unclear.

Conclusion

Statins should not be given routinely to patients with SLE. Potential immunomodulating effects of statins have not been convincingly established. Although the effects of statins on subclinical atheroma remain unclear and no studies have demonstrated the efficacy of statin therapy as primary or secondary cardiovascular prevention, we believe a serum lipid profile must be obtained once a year in every SLE patient. We agree with recommendations that the LDL-cholesterol level be kept below 100 mg/dL

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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