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A comparison of low and high dose atorvastatin on lipoproteins and inflammatory cytokines: The protection against nephropathy in diabetes with atorvastatin (panda) trial
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Abstracts / Atherosclerosis 241 (2015) e149ee229
treatments for key risk factors, such as hypertension, diabetes, and lipid abnormalities is critical to reduce future complications. Objective: To identify prevalence of lipid abnormalities and unmet needs among ACS patients in Germany currently receiving lipid lowering therapy (LLT) in light of aggressive goals recommended by new guidelines. Methods: DYSIS II is a multicenter, observational cross-sectional study conducted from May 2013-July 2014 in 22 German hospitals. Eligible adult patients were hospitalized for an ACS event, had full lipid profile available within 24 hours of admission, on LLT 3 months or not treated at all, not participating in randomized clinical trials involving medication, and were alive at discharge. Patient characteristics, risk factors, treatment patterns, and laboratory values were collected. Low density lipoprotein cholesterol (LDL-C) target achievement was assessed based on 2011 ESC/EAS guidelines. Results: Among 461 ACS patients (75.5% male, mean age 64.1 years), 80.9% had hypertension, 63.5% hypercholesterolemia, 56.9% history of coronary heart disease, 29.0% type 2 diabetes, and 27.3% were current smokers. 270 patients were on LLT, with only 21.9% reaching <70 mg/dl LDL-C target. Mean atorvastatin-equivalent dose was 18±11mg/day and 5.2% of treated patients received ezetimibe plus statin. Conclusion: More than three-fourths of LLT treated ACS patients in Germany were unable to achieve LDL-C target. Additional effective lipid lowering strategies are needed among these very high risk patients for LDL-C target achievement.
EAS-0434. A COMPARISON OF LOW AND HIGH DOSE ATORVASTATIN ON LIPOPROTEINS AND INFLAMMATORY CYTOKINES: THE PROTECTION AGAINST NEPHROPATHY IN DIABETES WITH ATORVASTATIN (PANDA) TRIAL H. Soran 1, Y. Liu 1, T. Siahmansur 1, J. Schofield 1,*, S. Kwok 2, V. CharltonMenys 1, M. Gittins 3, M. Gibson 4, N. Younis 5, M. France 6, P.N. Durrington 1, M.K. Rutter 3. 1 Lipoprotein Research Group, University of Manchester, Manchester, United Kingdom; 2 Cardiovascular Trials Unit, Central Manchester University Hospitals, Manchester, United Kingdom; 3 Manchester Diabetes Centre, Central Manchester University Hospitals, Manchester, United Kingdom; 4 Diabetes & Endocrinology, Salford Royal NHS Foundation Trust, Manchester, United Kingdom; 5 Diabetes & Endocrinology, University Hospital South Manchester, Manchester, United Kingdom; 6 Clinical Biochemistry, Central Manchester University Hospitals, Manchester, United Kingdom
* Corresponding author. Aim: To investigate the frequency with which recommended treatment goals are met in high risk diabetic patients with conventional dose as opposed to high dose statin therapy and their different effects on lipoproteins and other cardiovascular disease (CVD) risk factors. Methods: Patients with type 2 diabetes and optimally treated hypertension were randomized to receive atorvastatin 10mg (n¼59) or 80mg (n¼60) daily. Data at baseline and after one year are reported. Results: Patients in the study were at high CVD risk (observed annual event rate of 4.8%). The non-high density lipoprotein cholesterol (nonHDL-C) therapeutic goal of <2.6mmol/l was achieved by 72% of participants receiving 80mg daily, but only 40% on 10mg (p<0.005). Serum total cholesterol, low density lipoprotein cholesterol (LDL-C), apolipoprotein B100, glycated apolipoprotein B100 and lipoprotein-associated phospholipase A2 decreased significantly more on the higher dose. Serum apolipoprotein E and amyloid A decreased significantly only on 80mg daily. Both doses reduced triglycerides and oxidized LDL, and increased adiponectin, but these effects were not dose-dependent. Neither dose significantly affected cholesterol efflux, HDL-C, apolipoprotein A1, myeloperoxidase, high-sensitivity C-reactive protein (hsCRP), glycated hemoglobin (HbA1c) concentrations or the activities of paraoxonase-1, lecithin:cholesterol acyl transferase and cholesteryl ester transfer protein.
Conclusions: High dose atorvastatin is necessary to achieve non-HDL-C therapeutic goals in a substantial proportion of patients. Atorvastatin is effective, generally in a dose-dependent manner, in modifying LDL-related CVD risk factors. It has no effect on HDL-related parameters or hsCRP, but evidence that therapeutic modification of these is beneficial is currently largely lacking.
EAS-0440. PROTON PUMP INHIBITORS AND STATINS: A COMBINATION THAT FAVORS LDL-C REDUCTION? F. Barkas*, E. Liberopoulos, M. Kostapanos, C. Rizos, E. Klouras, M. Elisaf. Internal Medicine, School of Medicine University of Ioannina, Ioannina, Greece
* Corresponding author. Aim: Studies have shown that proton pump inhibitors (PPI) might influence the metabolism of cholesterol and statins in the liver. The aim of the present study was to record the impact of PPI use on low density lipoprotein cholesterol (LDL-C) levels in statin treated individuals. Methods: This was an observational study including adults followed for 3 years. LDL-C reduction was recorded in those receiving statin þ PPI and statin alone at the most recent visit. Results: Of 755 statin treated subjects, 8% were also taking PPI. There was no difference between 2 groups regarding the kind of statin therapy (Table 1.) Those receiving statin þ PPI had a higher LDL-C reduction by 5% compared with those taking only statin (p <0.05, after adjusting for the effect of gender, age and baseline LDL-C levels). In subgroup analysis among each kind of statin, the difference was significant only for those receiving rosuvastatin (8%). Conclusion: The PPI use might increase the statin effect (mainly of rosuvastatin) regarding the LDL-C reduction. This favorable impact of PPIs on lipidemic profile must be documented by prospective clinical studies.
Table 1 Comparison of lipid-lowering therapy in individuals receiving statin + PPI and those taking only statin
Atorvastatin Rosuvastatin Simvastatin Fluvastatin Ezetimibe
Statin (N¼700)
Statin + PPI (N¼55)
N, %
Median dose, mg
N, %
Median dose, mg
42 31 22 4 21
20 20 40 80 10
36 36 26 2 24
20 10 40 80 10
EAS-0446. PREDICTING THE REDUCTION IN RISK OF CARDIOVASCULAR EVENTS WITH HIGH-INTENSITY STATIN TREATMENT: A VOYAGER ANALYSIS B.W. Karlson 1, *, M.K. Palmer 2, S.J. Nicholls 3, P. Lundman 4, P.J. €lndal, and Department of Molecular and Barter 5. 1 AstraZeneca Mo Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden; 2 School of Computing and Mathematics, Keele University, Keele, United Kingdom; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia; 4 Danderyd Hospital, Karolinska Institute, Stockholm, Sweden; 5 Centre for Vascular Research, University of New South Wales, Sydney, Australia
* Corresponding author.
Abstracts / Atherosclerosis 241 (2015) e149ee229
treatments for key risk factors, such as hypertension, diabetes, and lipid abnormalities is critical to reduce future complications. Objective: To identify prevalence of lipid abnormalities and unmet needs among ACS patients in Germany currently receiving lipid lowering therapy (LLT) in light of aggressive goals recommended by new guidelines. Methods: DYSIS II is a multicenter, observational cross-sectional study conducted from May 2013-July 2014 in 22 German hospitals. Eligible adult patients were hospitalized for an ACS event, had full lipid profile available within 24 hours of admission, on LLT 3 months or not treated at all, not participating in randomized clinical trials involving medication, and were alive at discharge. Patient characteristics, risk factors, treatment patterns, and laboratory values were collected. Low density lipoprotein cholesterol (LDL-C) target achievement was assessed based on 2011 ESC/EAS guidelines. Results: Among 461 ACS patients (75.5% male, mean age 64.1 years), 80.9% had hypertension, 63.5% hypercholesterolemia, 56.9% history of coronary heart disease, 29.0% type 2 diabetes, and 27.3% were current smokers. 270 patients were on LLT, with only 21.9% reaching <70 mg/dl LDL-C target. Mean atorvastatin-equivalent dose was 18±11mg/day and 5.2% of treated patients received ezetimibe plus statin. Conclusion: More than three-fourths of LLT treated ACS patients in Germany were unable to achieve LDL-C target. Additional effective lipid lowering strategies are needed among these very high risk patients for LDL-C target achievement.
EAS-0434. A COMPARISON OF LOW AND HIGH DOSE ATORVASTATIN ON LIPOPROTEINS AND INFLAMMATORY CYTOKINES: THE PROTECTION AGAINST NEPHROPATHY IN DIABETES WITH ATORVASTATIN (PANDA) TRIAL H. Soran 1, Y. Liu 1, T. Siahmansur 1, J. Schofield 1,*, S. Kwok 2, V. CharltonMenys 1, M. Gittins 3, M. Gibson 4, N. Younis 5, M. France 6, P.N. Durrington 1, M.K. Rutter 3. 1 Lipoprotein Research Group, University of Manchester, Manchester, United Kingdom; 2 Cardiovascular Trials Unit, Central Manchester University Hospitals, Manchester, United Kingdom; 3 Manchester Diabetes Centre, Central Manchester University Hospitals, Manchester, United Kingdom; 4 Diabetes & Endocrinology, Salford Royal NHS Foundation Trust, Manchester, United Kingdom; 5 Diabetes & Endocrinology, University Hospital South Manchester, Manchester, United Kingdom; 6 Clinical Biochemistry, Central Manchester University Hospitals, Manchester, United Kingdom
* Corresponding author. Aim: To investigate the frequency with which recommended treatment goals are met in high risk diabetic patients with conventional dose as opposed to high dose statin therapy and their different effects on lipoproteins and other cardiovascular disease (CVD) risk factors. Methods: Patients with type 2 diabetes and optimally treated hypertension were randomized to receive atorvastatin 10mg (n¼59) or 80mg (n¼60) daily. Data at baseline and after one year are reported. Results: Patients in the study were at high CVD risk (observed annual event rate of 4.8%). The non-high density lipoprotein cholesterol (nonHDL-C) therapeutic goal of <2.6mmol/l was achieved by 72% of participants receiving 80mg daily, but only 40% on 10mg (p<0.005). Serum total cholesterol, low density lipoprotein cholesterol (LDL-C), apolipoprotein B100, glycated apolipoprotein B100 and lipoprotein-associated phospholipase A2 decreased significantly more on the higher dose. Serum apolipoprotein E and amyloid A decreased significantly only on 80mg daily. Both doses reduced triglycerides and oxidized LDL, and increased adiponectin, but these effects were not dose-dependent. Neither dose significantly affected cholesterol efflux, HDL-C, apolipoprotein A1, myeloperoxidase, high-sensitivity C-reactive protein (hsCRP), glycated hemoglobin (HbA1c) concentrations or the activities of paraoxonase-1, lecithin:cholesterol acyl transferase and cholesteryl ester transfer protein.
Conclusions: High dose atorvastatin is necessary to achieve non-HDL-C therapeutic goals in a substantial proportion of patients. Atorvastatin is effective, generally in a dose-dependent manner, in modifying LDL-related CVD risk factors. It has no effect on HDL-related parameters or hsCRP, but evidence that therapeutic modification of these is beneficial is currently largely lacking.
EAS-0440. PROTON PUMP INHIBITORS AND STATINS: A COMBINATION THAT FAVORS LDL-C REDUCTION? F. Barkas*, E. Liberopoulos, M. Kostapanos, C. Rizos, E. Klouras, M. Elisaf. Internal Medicine, School of Medicine University of Ioannina, Ioannina, Greece
* Corresponding author. Aim: Studies have shown that proton pump inhibitors (PPI) might influence the metabolism of cholesterol and statins in the liver. The aim of the present study was to record the impact of PPI use on low density lipoprotein cholesterol (LDL-C) levels in statin treated individuals. Methods: This was an observational study including adults followed for 3 years. LDL-C reduction was recorded in those receiving statin þ PPI and statin alone at the most recent visit. Results: Of 755 statin treated subjects, 8% were also taking PPI. There was no difference between 2 groups regarding the kind of statin therapy (Table 1.) Those receiving statin þ PPI had a higher LDL-C reduction by 5% compared with those taking only statin (p <0.05, after adjusting for the effect of gender, age and baseline LDL-C levels). In subgroup analysis among each kind of statin, the difference was significant only for those receiving rosuvastatin (8%). Conclusion: The PPI use might increase the statin effect (mainly of rosuvastatin) regarding the LDL-C reduction. This favorable impact of PPIs on lipidemic profile must be documented by prospective clinical studies.
Table 1 Comparison of lipid-lowering therapy in individuals receiving statin + PPI and those taking only statin
Atorvastatin Rosuvastatin Simvastatin Fluvastatin Ezetimibe
Statin (N¼700)
Statin + PPI (N¼55)
N, %
Median dose, mg
N, %
Median dose, mg
42 31 22 4 21
20 20 40 80 10
36 36 26 2 24
20 10 40 80 10
EAS-0446. PREDICTING THE REDUCTION IN RISK OF CARDIOVASCULAR EVENTS WITH HIGH-INTENSITY STATIN TREATMENT: A VOYAGER ANALYSIS B.W. Karlson 1, *, M.K. Palmer 2, S.J. Nicholls 3, P. Lundman 4, P.J. €lndal, and Department of Molecular and Barter 5. 1 AstraZeneca Mo Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden; 2 School of Computing and Mathematics, Keele University, Keele, United Kingdom; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia; 4 Danderyd Hospital, Karolinska Institute, Stockholm, Sweden; 5 Centre for Vascular Research, University of New South Wales, Sydney, Australia
* Corresponding author.