Therapeutic Effects and Safety Profile of Atorvastatin on Psoriasis Severity Associated with Cardiovascular Risk

Abstract

Several studies occurs on anti-hyperlipidemic drug Atorvastatin and its pleotropic effects. However its relationship with Psoriasis and association of cardiovascular risk in comparison of standard therapy with large sample size has not been studied in Pakistan. Topical Betamethasone is the first line treatment in the management of all grades of Psoriasis as a monotherapy and in combination therapy. Beyond lipid lowering mechanism Atorvastatin have pleiotropic effect through direct inhibition of small GTPase protein (Rho, Rac, Ras and Rab). These protein control multiple signaling pathways involve in pathogenesis of immuno-inflammatory diseases like Psoriasis. Statin modulates the altered expression of these prenylated proteins. Psoriasis is important disease for researcher because it serves as a model disease to study the basic principle of immune mediated inflammation that is the reason by which in clinical trial it acts as a model for new research studies. Psoriasis is associated with other co-morbidities, the most important is cardiovascular risk. OBJECTIVE: Present study demonstrates that Atorvastatin has dual action on severity of psoriasis and cardiovascular risk (CVR). METHODS: This was an interventional study conducted in Pharmacology Department of BMSI, JPMC with the collaboration of Pathology Department, BMSI, JPMC and Dermatology Department of JPMC. This research project consist of two phases one was the preclinical conducted on ninety adult Wistar Albino rats divided into three groups, Group A (Control), Group B (Doxorubicin induced toxicity) and Group C (Atorvastatin pretreated). Other was the clinical study on mild to moderate xxvi plaque type psoriatic patients. 225 psoriatic patients enrolled in this study those who fulfilled the inclusion and exclusion criteria. The inclusion criteria were, both male and female age ranging from 25-65 years, PASI score <12, hs C-RP ≥ 3. These patients further divided into three groups. Group A prescribed tab. Atorvastatin 80mg for first three month followed by 40mg for next three months. Group B prescribed Placebo and topical Betamethasone valerate 0.1% twice daily for 3 months and once a day for the next 3 months (three weeks apply than one week interval and for sensitive area 50% betamethasone in soft paraffin). Group C prescribed tab. Atorvastatin 40mg for the first three months followed by 20 mg for next three months plus topical Betamethasone valerate 0.1% once daily for 6 months (three weeks apply than one week interval and for sensitive area 50% betamethasone in soft paraffin). The efficacy and safety profile of drug assists preclinically by biopsy of rats myocardium and clinically by PASI, hsCRP, DLQI, Lipid Profile, LFTs and CPK.