Comparison of the efficacy and tolerability of rosuvastatin with atorvastatin in patients with hypercholesterolaemia: the discovery Penta study

Universidade Federal de São Paulo, São Paulo, BrazilAstraZeneca, Macclesfield, Cheshire, EnglandUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The D9N polymorphism of lipoprotein lipase gene is a marker for myocardial infarction in diabetics

Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C value - an Evaluation of Rosuvastatin therapY compared with atorvastatin

Background. International guidelines emphasize the need to achieve recommended low-density lipoprotein cholesterol (LDL-C) levels in order to reduce morbidity and mortality associated with coronary heart disease (CHD). However, many patients with hypercholesterolemia fail to achieve LDL-C goals on treatment.Objective: the primary objective was to compare the efficacy of rosuvastatin and atorvastatin for enabling patients to achieve National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals. Secondary objectives were European LDL-C goal achievement, changes in the lipid profile, and safety. Research design and methods: This 12-week, multicenter, multinational, randomized, open-label trial compared the efficacy and safety of rosuvastatin 10 mg with atorvastatin 10 mg in statin-naive and switched patients with primary hypercholesterolemia from Brazil, Colombia, Mexico, Portugal, and Venezuela.Results: A total of 1124 patients with similar baseline characteristics were randomized to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving rosuvastatin 10mg compared with atorvastatin 10 mg achieved NCEP ATP III LDL-C goals (71.2% vs 61.4%, p < 0.001), 1998 European LDL-C goals (73.5% vs 59.2%, p < 0.001) and 2003 European LDL-C goals (58.9% vs 44.6%, p < 0.001). Rosuvastatin treatment was associated with significant reductions in LDL-C and total cholesterol (TC) and, in statin-naive patients, a significant increase in high-density lipoprotein cholesterol (HDL-C) compared with atorvastatin treatment. Both treatments were well tolerated with a similar incidence of adverse events. Clinically significant elevations in creatinine, creatine kinase or hepatic transaminases were low and similar between treatment groups.Conclusions: Rosuvastatin 10 mg is significantly more effective at achieving NCEP ATP III and European LDL-C goals, lowering LDL-C and TC in both naive and switched patients and increasing HDL-C in naive patients than atorvastatin 10 mg, with a similar safety and tolerability profile. This study also provides evidence regarding the comparative effects of rosuvastatin versus atorvastatin in Latin American and Portuguese populations.Universidade Federal de São Paulo, São Paulo, BrazilPontificia Univ Javeriana, Med Interna & Epidemiol Clin, Bogota, ColombiaUniv Guadalajara, Guadalajara 44430, Jalisco, MexicoUniv Coimbra, Serv Med 2, P-3000 Coimbra, PortugalHosp Miguel Perez Carreno, Serv Nefrol Dialisis & Transplante, Caracas, VenezuelaAstraZeneca, Macclesfield, Cheshire, EnglandUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. The aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC). Methods and Results: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24 h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C-max], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C-max, P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C. on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). In addition, clopidogrel C-max was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found. Conclusions: The balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease. (Circ J 2012; 76: 729-736)763729736Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq