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Efficacy and safety of pitavastatin in paediatric FH compared with other statins from Cochrane Database
Abstracts / Atherosclerosis 252 (2016) e197ee235
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Objectives: Large-scale prospective studies have shown that sugarsweetened beverages (SSB) consumption is linked to cardiovascular risk in the general population. Our objective was to explore the prevalence and the 2010-15 secular trends in SSB sales in 43 European and Middle East countries. Methods: We used data from beverages sales from the Euromonitor Passport International Database. SSBs were defined as in-trade and offtrade caloric soft drinks, fruit juice and sports and energy drinks. Results are reported as liters per capita (LPC). Results: In 2015, SSB sales were highest in Saudi Arabia (124,9 LPC) followed by Belgium (96,2) and Ireland (95,6) and lowest in Morocco (20,5), Ukraine (23,9) and Egypt (25,7). Between 2010 and 2015, SSB sales decreased in all (17/17) Western European countries, in most Eastern European countries (14/18) and in two Middle East countries (2/ 8). During that period, the largest absolute increase in SSB sales was observed in Saudi Arabia (23,2), Georgia (20,5) and the United Arab Emirates (16,6). On the other hand, the largest absolute decreases were observed in Greece (-20,0), Croatia (-16,5) and Portugal (-15,6). While caloric soft drinks and fruit juice sales decreased in most countries (with marked heterogeneity across both European and Middle East countries), energy drinks sales increased in all countries (except Finland). Conclusions: Although SSB consumption is slowly but steadily decreasing in Western Europe, and to a lesser extent in Eastern Europe, SSB consumption is increasing in most Middle East Countries. Energy drinks consumption is increasing steadily across Europe and the Middle East. Ă
EAS16-0241, PHARMACOLOGY OF DYSLIPIDEMIA. ATTAINMENT OF ACCAHA RECOMMENDED LDL C LOWERING WITH STATIN AND EZETIMIBE STATIN THERAPIES P. Toth 1, H. Bays 2, M. Farnier 3, E. Jensen 4, J. Tomassini 4, A. Polis 4, J. Foody 4, A. Tershakovec 4. 1 Univ.of Illinois College of Med., Chief of Medicine-CGH Medical Center, Sterling, USA; 2 L-MARC Research Center, Metabolic and Atherosclerosis Research, Louisville, USA; 3 Point Medical Rond Point de la Nation, Cardiology, Dijon, France; 4 Merck and Co.- Inc., Clinical Research, Kenilworth, USA Objectives: The ACC/AHA 2013 cholesterol guidelines specify treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of 50% and 30 with high- and moderate-intensity statin therapies, respectively. The LDL-C-lowering responses to statin and ezetimibe+statin therapies for these parameters were evaluated in statin-naïve, hypercholesterolemic patients. Methods: Data pooled from 14 randomized, controlled, double-blind trials in hypercholesterolemic patients were categorized per the 4 risk groups specified by ACC/AHA 2013 guidelines: 1)atherosclerotic cardiovascular disease (ASCVD), 2)baseline LDL-C >190 mg/dL, 3)diabetes and 4)10-year ASCVD risk 7.5% (no ASCVD or diabetes). Mean % LDL-C changes from baseline and percentage of patient attainment of LDL-C reductions 50% and 30% on recommended therapy (Figure¶k) among risk groups were assessed. Results: Across risk groups, mean % LDL-C changes from baseline ranged from -49.5 to -52.2% and -37.7 to -40.5% for high-and moderate-intensity therapy with statins, and from -55.1 to 57.5% and -43.3 to -47.7% with ezetimibe+statins, respectively. Percentages of patients who achieved LDLC reductions 50% on high-intensity therapy were 62.2 to 70.2% for statins and 74.2 to 82.9% for ezetimibe+statins, and on moderate-intensity therapy were 23.1 to 28.7% for statins and 34.0 to 42.1% for ezetimibe+statins (Figure). Attainment of reductions 30% was similar for statins (76.8 to 94.5%) and ezetimibe+statins (86.2 to 96.7%). Conclusions: Overall, ~1/3 of patients on high-intensity statin therapy did not achieve LDL-C reductions 50%; attainment was greater with ezetimibe+statins. Given the range of LDL-C lowering observed within the lipid-lowering intensity groups, these results highlight the importance of assessing patient responses to cholesterol-lowering therapy.
EAS16-0149, PHARMACOLOGY OF DYSLIPIDEMIA. EFFICACY AND SAFETY OF PITAVASTATIN IN PAEDIATRIC FH COMPARED WITH OTHER STATINS FROM COCHRANE DATABASE M. Harada-Shiba 1, T. Ohta 2, A. Ohtake 3, T. Okada 4, O. Arisaka 5, J. Kastelein 6, I. Luirink 6. 1 National Cerebral and Cardiovascular Center Research Institute, Department of Molecular Innovation in Lipidology, Suita, Osaka, Japan; 2 University of Ryukyus, Department of Child Health and Welfare, Naha, Japan; 3 Saitama Medical University, Department of Pediatrics, Saitama, Japan; 4 Nihon University School of Medicine, Department of Pediatric and Child Health, Tokyo, Japan; 5 Dokkyo Medical University School of Medicine, Department of Pediatrics, Tochigi, Japan; 6 Academic Medical Center-Amsterdam, Department of Vascular Medicine, Amsterdam, Netherlands Objectives: Pitavastatin is the latest statin, which was initially approved in Japan and subsequently in Europe and the US, and elsewhere worldwide. It has an indication in paediatric FH ages 10 years and older since June 2015 for the first time in Japan. It has recently completed an EU Paediatric Investigation Plan. However the efficacy and safety profiles of pitavastatin in paediatric FH has not been fully established yet. Our aim is to compare with other statins for paediatric patients with FH in terms of efficacy and safety. Methods: We compared the efficacy and safety data between pitavastatin from three clinical studies carried out in Japan and Europe and other statins from Cochrane Database. The efficacy endpoint were percent change from baseline in LDL-C, TC, TG and HDL-C. Safety endpoint were the rate of adverse drug reaction, summary of laboratory results such as CK, AST, ALT, testosterone and estradiol, and Tanner staging. Results: The percent change in LDL-C from baseline to the end of study was from 23.5% to 39.3% in pitavastatin groups whereas other statins’ was -32.2%. Other efficacy parameter such as TC, TG and HDL-C were also similar among them. There were no significant concern in the rate of adverse drug reactions, laboratory values of CK, AST, ALT, testosterone and estradiol, and the Tanner stages during the study in pitavastatin groups as well as other statins.
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Abstracts / Atherosclerosis 252 (2016) e197ee235
Conclusions: Efficacy and safety of pitavastain in paediatric FH were comparable to these of other statins, indicating similar availability as other statins.
EAS16-0352, PHARMACOLOGY OF DYSLIPIDEMIA. HOW TO IMPROVE THE CHOLESTEROL-LOWERING EFFICACY OF EZETIMIBE IN STATIN-INTOLERANT PATIENTS IN CLINICAL PRACTICE: A RETROSPECTIVE STUDY A. Cicero, M. Morbini, S. D'Addato, F. Fogacci, M. Rosticci, C. Borghi. Policlinico Sant'Orsola-Malpighi, Medicine and Surgery Sciences Dept., Bologna, Italy Objectives: Statin interruption is a relevant cause of prevention failure and increased costs. The main aim of our study was to evaluate the tolerability and efficacy of alternative approaches to reduce hypercholesterolemia in patients affected from statin-related myalgia. Methods: We retrospectively evaluated 3534 CRFs filled in the period January 2012-December 2014 for first visits by the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: hypercholesterolemia requiring pharmacological treatment, statin-related myalgia, previous failed treatment with at least two statins at low dosage, well-tolerated baseline treatment with Ezetimibe 10 mg 1 tablet/day. Then, a number of alternative treatments have been added to the ezetimibe one. Results: Almost 50% of the patients treated with Fenofibrate 145 mg/day, Rosuvastatin 5 mg 2 tablets/week, Red Yeast Rice + Berberine 500 mg, and Berberine 500 mg b.i.d. associated to Ezetimibe reached the LDL-C target foreseen for their CVD risk class, while the percentage was lower for those treated with Rosuvastatin 5 mg once a week or Phytosterols 900 mg + Psyllium fiber 3.5 gr b.i.d. In patients with residual tolerable myalgia (N. 52), the treatment with CoQ10 for 8 weeks determined a mean improvement of the graduated myalgia score from 4,8±1,9 to 2,9±1,3 (p¼0.013), without significant difference among different lipid-lowering drug groups. Myalgia ceased in 18/ 52 subjects. Conclusions: In a large part of statin intolerant subjects is possible to improve ezetimibe efficacy with alternative treatment protocols. Coenzyme Q10 nanoemulsions improves the tolerability of myalgia in a large part of patients.
EAS16-0796, PHARMACOLOGY OF DYSLIPIDEMIA. IDENTIFICATION AND MANAGEMENT OF CANADIAN PATIENTS WITH SYMPTOMS OF STATIN INTOLERANCE: RESULTS FROM A REAL-WORLD CLINICAL PRACTICE SURVEY P. Oh 1, G.K. Hovingh 2, S.R. Gandra 3, J. McKendrick 4, R. Dent 5, H.M. Wieffer 4, A.L. Catapano 6, R.S. Rosenson 7, E.S.G. Stroes 2. 1 Toronto Rehabilitation Institute, Cardiac Rehabilitation and Secondary Prevention Program, Toronto, Canada; 2 Academic Medical Center, Department of Vascular Medicine, Amsterdam, Netherlands; 3 Amgen Inc., Global Health Economics, Thousand Oaks, USA; 4 PRMA Consulting Ltd, Real-world Evidence, Fleet, United Kingdom; 5 Amgen Inc., Development, Zug, Switzerland; 6 University of Milan and IRCCS Multimedica, Department of Pharmacological and Biomolecular Sciences, Milan, Italy; 7 Mount Sinai Icahn School of Medicine, Department of Medicine - Cardiology, New York, USA Objectives: To understand how clinicians based in Canada identify and manage patients with statin intolerance (SI). Methods: A 45-minute web-based survey was conducted in 13 countries between January-February 2014; only results from Canada are presented here. Both specialists (cardiologists; endocrinologists) and primary care physicians (PCPs) participated; they were required to have treated 75 and 50 patients with hypercholesterolemia, respectively, in the previous 12 months, and 5 patients presenting with SI symptoms. All participants provided informed consent.
Results: Sixty Canadian clinicians completed the survey (67% specialists). Muscle-related symptoms (MRS) were the most common symptoms in patients with potential SI (82%). Common lab abnormalities included persistent transaminase elevation (23%) and elevated creatinine kinase (CK) without MRS (27%). For patients with MRS, statin rechallenge or trying 2 alternative statins were each considered by 70% of clinicians to be “very” or “extremely important” to establish SI. Most clinicians (82%) reported using more stringent criteria to establish SI in patients at high risk of a CV event. Respondents estimated that an average of 57% of patients with confirmed SI and at high risk of CV events would continue with lowdose statins, with or without another lipid-lowering therapy (LLT); 30% would receive only a non-statin LLT and 14% no LLT. Most clinicians (67%) reported using Canadian Cardiovascular Society guidelines for lipid management in these patients. Conclusions: Canadian clinicians use several strategies to establish SI and continue LLT in these patients. Only a minority of patients with SI receive no LLT, putting them at high risk of a CV event.
EAS16-0775, PHARMACOLOGY OF DYSLIPIDEMIA. PCSK9 CIRCULATING LEVELS AND CETP PLASMA ACTIVITY ARE ASSOCIATED INDEPENDENTLY OF LIPID LOWERING THERAPIES 2, M. Heras 1, L. J. Girona 1, D. Ibarretxe 1, N. Plana 1, S. Guaita 1, N. Amigo Masana 1. 1 Sant Joan University Hospital, Universitat Rovira i Virgili-IISPV, CIBERDEM, Vascular Medicine and Metabolism Unit-Research Unit on Lipids and Atherosclerosis, Reus, Spain; 2 Universitat Rovira i Virgili-IISPV, Biosfer Teslab, Department of Electronic Engineering, Reus, Spain Objectives: PCSK9 inhibition is a new powerful cholesterol-lowering therapy. Recently, it has been communicate that CETP inhibitors could influence PCSK9 levels as off-target effect. We have explored the relationship of PCSK9 levels and CETP activity in patients with metabolic diseases not on lipid lowering therapy. Methods: Plasma CETP activity and PCSK9 levels were measured in 450 participants (mean age, 58 years; 49% women) who attended the metabolism unit because, metabolic syndrome (MetS) (78%), atherogenic dyslipidemia (32%), obesity (50%), diabetes (72%), and other risk factors (13%) after six week lipid lowering drug wash-out period. Results: Plasma PCSK9 levels and CETP activity were significantly elevated in MetS (12,4%, p¼0,004 and 11,2%, p<0,0001, respectively). Remarkably, plasma PCSK9 levels were positively correlated with CETP activity in whole population (r¼0,256, p<0,0001) independently of age, gender, body mass index (BMI), systolic blood pressure (SBP), triglycerides, LDL-C and glucose. Individuals with the loss-of-function PCSK9 genetic variant rs11591147 (R46L) that have lower levels of PCSK9 (36,5%, p<0,0001) and LDL-C (17,8%, P¼0,010) also was accompanied with lower CETP activity (10,31%, p¼0,009). In multiple regression analysis, this association remained significant even after adjusting for gender, age, BMI, triglycerides, LDL-C, glucose, LCAT, SBP and MetS (p¼0,003). Conclusions: Our data reveal a significant association between PCSK9 and CETP regardless of lipid lowering treatment. This association is maintained in patients with lower PCSK9 genetically determined. The clinical implications of this metabolic relationship could be of interest, explaining in part the effect of PCSK9 and CETP inhibition on overall lipid profile.
EAS16-0488, PHARMACOLOGY OF DYSLIPIDEMIA. UNDERSTANDING LIPOPROTEIN(A) METABOLISM: REBOUND ANALYSES OF LIPOPROTEIN(A) AND PCSK9 CONCENTRATIONS FOLLOWING REGULAR LIPOPROTEIN APHERESIS TREATMENT (THE LIPARE-STUDY) E. Waldmann 1, E.M. Ooi 2, P.H.R. Barrett 2, D.C. Chan 2, S.M. Marcovina 3, G.F. Watts 2, K.G. Parhofer 1. 1 Ludwig-Maximilians-University Munich, Department for internal medicine II, Munich, Germany; 2 University of Western Australia, School of Medicine and Pharmacology,
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Objectives: Large-scale prospective studies have shown that sugarsweetened beverages (SSB) consumption is linked to cardiovascular risk in the general population. Our objective was to explore the prevalence and the 2010-15 secular trends in SSB sales in 43 European and Middle East countries. Methods: We used data from beverages sales from the Euromonitor Passport International Database. SSBs were defined as in-trade and offtrade caloric soft drinks, fruit juice and sports and energy drinks. Results are reported as liters per capita (LPC). Results: In 2015, SSB sales were highest in Saudi Arabia (124,9 LPC) followed by Belgium (96,2) and Ireland (95,6) and lowest in Morocco (20,5), Ukraine (23,9) and Egypt (25,7). Between 2010 and 2015, SSB sales decreased in all (17/17) Western European countries, in most Eastern European countries (14/18) and in two Middle East countries (2/ 8). During that period, the largest absolute increase in SSB sales was observed in Saudi Arabia (23,2), Georgia (20,5) and the United Arab Emirates (16,6). On the other hand, the largest absolute decreases were observed in Greece (-20,0), Croatia (-16,5) and Portugal (-15,6). While caloric soft drinks and fruit juice sales decreased in most countries (with marked heterogeneity across both European and Middle East countries), energy drinks sales increased in all countries (except Finland). Conclusions: Although SSB consumption is slowly but steadily decreasing in Western Europe, and to a lesser extent in Eastern Europe, SSB consumption is increasing in most Middle East Countries. Energy drinks consumption is increasing steadily across Europe and the Middle East. Ă
EAS16-0241, PHARMACOLOGY OF DYSLIPIDEMIA. ATTAINMENT OF ACCAHA RECOMMENDED LDL C LOWERING WITH STATIN AND EZETIMIBE STATIN THERAPIES P. Toth 1, H. Bays 2, M. Farnier 3, E. Jensen 4, J. Tomassini 4, A. Polis 4, J. Foody 4, A. Tershakovec 4. 1 Univ.of Illinois College of Med., Chief of Medicine-CGH Medical Center, Sterling, USA; 2 L-MARC Research Center, Metabolic and Atherosclerosis Research, Louisville, USA; 3 Point Medical Rond Point de la Nation, Cardiology, Dijon, France; 4 Merck and Co.- Inc., Clinical Research, Kenilworth, USA Objectives: The ACC/AHA 2013 cholesterol guidelines specify treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of 50% and 30 with high- and moderate-intensity statin therapies, respectively. The LDL-C-lowering responses to statin and ezetimibe+statin therapies for these parameters were evaluated in statin-naïve, hypercholesterolemic patients. Methods: Data pooled from 14 randomized, controlled, double-blind trials in hypercholesterolemic patients were categorized per the 4 risk groups specified by ACC/AHA 2013 guidelines: 1)atherosclerotic cardiovascular disease (ASCVD), 2)baseline LDL-C >190 mg/dL, 3)diabetes and 4)10-year ASCVD risk 7.5% (no ASCVD or diabetes). Mean % LDL-C changes from baseline and percentage of patient attainment of LDL-C reductions 50% and 30% on recommended therapy (Figure¶k) among risk groups were assessed. Results: Across risk groups, mean % LDL-C changes from baseline ranged from -49.5 to -52.2% and -37.7 to -40.5% for high-and moderate-intensity therapy with statins, and from -55.1 to 57.5% and -43.3 to -47.7% with ezetimibe+statins, respectively. Percentages of patients who achieved LDLC reductions 50% on high-intensity therapy were 62.2 to 70.2% for statins and 74.2 to 82.9% for ezetimibe+statins, and on moderate-intensity therapy were 23.1 to 28.7% for statins and 34.0 to 42.1% for ezetimibe+statins (Figure). Attainment of reductions 30% was similar for statins (76.8 to 94.5%) and ezetimibe+statins (86.2 to 96.7%). Conclusions: Overall, ~1/3 of patients on high-intensity statin therapy did not achieve LDL-C reductions 50%; attainment was greater with ezetimibe+statins. Given the range of LDL-C lowering observed within the lipid-lowering intensity groups, these results highlight the importance of assessing patient responses to cholesterol-lowering therapy.
EAS16-0149, PHARMACOLOGY OF DYSLIPIDEMIA. EFFICACY AND SAFETY OF PITAVASTATIN IN PAEDIATRIC FH COMPARED WITH OTHER STATINS FROM COCHRANE DATABASE M. Harada-Shiba 1, T. Ohta 2, A. Ohtake 3, T. Okada 4, O. Arisaka 5, J. Kastelein 6, I. Luirink 6. 1 National Cerebral and Cardiovascular Center Research Institute, Department of Molecular Innovation in Lipidology, Suita, Osaka, Japan; 2 University of Ryukyus, Department of Child Health and Welfare, Naha, Japan; 3 Saitama Medical University, Department of Pediatrics, Saitama, Japan; 4 Nihon University School of Medicine, Department of Pediatric and Child Health, Tokyo, Japan; 5 Dokkyo Medical University School of Medicine, Department of Pediatrics, Tochigi, Japan; 6 Academic Medical Center-Amsterdam, Department of Vascular Medicine, Amsterdam, Netherlands Objectives: Pitavastatin is the latest statin, which was initially approved in Japan and subsequently in Europe and the US, and elsewhere worldwide. It has an indication in paediatric FH ages 10 years and older since June 2015 for the first time in Japan. It has recently completed an EU Paediatric Investigation Plan. However the efficacy and safety profiles of pitavastatin in paediatric FH has not been fully established yet. Our aim is to compare with other statins for paediatric patients with FH in terms of efficacy and safety. Methods: We compared the efficacy and safety data between pitavastatin from three clinical studies carried out in Japan and Europe and other statins from Cochrane Database. The efficacy endpoint were percent change from baseline in LDL-C, TC, TG and HDL-C. Safety endpoint were the rate of adverse drug reaction, summary of laboratory results such as CK, AST, ALT, testosterone and estradiol, and Tanner staging. Results: The percent change in LDL-C from baseline to the end of study was from 23.5% to 39.3% in pitavastatin groups whereas other statins’ was -32.2%. Other efficacy parameter such as TC, TG and HDL-C were also similar among them. There were no significant concern in the rate of adverse drug reactions, laboratory values of CK, AST, ALT, testosterone and estradiol, and the Tanner stages during the study in pitavastatin groups as well as other statins.
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Abstracts / Atherosclerosis 252 (2016) e197ee235
Conclusions: Efficacy and safety of pitavastain in paediatric FH were comparable to these of other statins, indicating similar availability as other statins.
EAS16-0352, PHARMACOLOGY OF DYSLIPIDEMIA. HOW TO IMPROVE THE CHOLESTEROL-LOWERING EFFICACY OF EZETIMIBE IN STATIN-INTOLERANT PATIENTS IN CLINICAL PRACTICE: A RETROSPECTIVE STUDY A. Cicero, M. Morbini, S. D'Addato, F. Fogacci, M. Rosticci, C. Borghi. Policlinico Sant'Orsola-Malpighi, Medicine and Surgery Sciences Dept., Bologna, Italy Objectives: Statin interruption is a relevant cause of prevention failure and increased costs. The main aim of our study was to evaluate the tolerability and efficacy of alternative approaches to reduce hypercholesterolemia in patients affected from statin-related myalgia. Methods: We retrospectively evaluated 3534 CRFs filled in the period January 2012-December 2014 for first visits by the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: hypercholesterolemia requiring pharmacological treatment, statin-related myalgia, previous failed treatment with at least two statins at low dosage, well-tolerated baseline treatment with Ezetimibe 10 mg 1 tablet/day. Then, a number of alternative treatments have been added to the ezetimibe one. Results: Almost 50% of the patients treated with Fenofibrate 145 mg/day, Rosuvastatin 5 mg 2 tablets/week, Red Yeast Rice + Berberine 500 mg, and Berberine 500 mg b.i.d. associated to Ezetimibe reached the LDL-C target foreseen for their CVD risk class, while the percentage was lower for those treated with Rosuvastatin 5 mg once a week or Phytosterols 900 mg + Psyllium fiber 3.5 gr b.i.d. In patients with residual tolerable myalgia (N. 52), the treatment with CoQ10 for 8 weeks determined a mean improvement of the graduated myalgia score from 4,8±1,9 to 2,9±1,3 (p¼0.013), without significant difference among different lipid-lowering drug groups. Myalgia ceased in 18/ 52 subjects. Conclusions: In a large part of statin intolerant subjects is possible to improve ezetimibe efficacy with alternative treatment protocols. Coenzyme Q10 nanoemulsions improves the tolerability of myalgia in a large part of patients.
EAS16-0796, PHARMACOLOGY OF DYSLIPIDEMIA. IDENTIFICATION AND MANAGEMENT OF CANADIAN PATIENTS WITH SYMPTOMS OF STATIN INTOLERANCE: RESULTS FROM A REAL-WORLD CLINICAL PRACTICE SURVEY P. Oh 1, G.K. Hovingh 2, S.R. Gandra 3, J. McKendrick 4, R. Dent 5, H.M. Wieffer 4, A.L. Catapano 6, R.S. Rosenson 7, E.S.G. Stroes 2. 1 Toronto Rehabilitation Institute, Cardiac Rehabilitation and Secondary Prevention Program, Toronto, Canada; 2 Academic Medical Center, Department of Vascular Medicine, Amsterdam, Netherlands; 3 Amgen Inc., Global Health Economics, Thousand Oaks, USA; 4 PRMA Consulting Ltd, Real-world Evidence, Fleet, United Kingdom; 5 Amgen Inc., Development, Zug, Switzerland; 6 University of Milan and IRCCS Multimedica, Department of Pharmacological and Biomolecular Sciences, Milan, Italy; 7 Mount Sinai Icahn School of Medicine, Department of Medicine - Cardiology, New York, USA Objectives: To understand how clinicians based in Canada identify and manage patients with statin intolerance (SI). Methods: A 45-minute web-based survey was conducted in 13 countries between January-February 2014; only results from Canada are presented here. Both specialists (cardiologists; endocrinologists) and primary care physicians (PCPs) participated; they were required to have treated 75 and 50 patients with hypercholesterolemia, respectively, in the previous 12 months, and 5 patients presenting with SI symptoms. All participants provided informed consent.
Results: Sixty Canadian clinicians completed the survey (67% specialists). Muscle-related symptoms (MRS) were the most common symptoms in patients with potential SI (82%). Common lab abnormalities included persistent transaminase elevation (23%) and elevated creatinine kinase (CK) without MRS (27%). For patients with MRS, statin rechallenge or trying 2 alternative statins were each considered by 70% of clinicians to be “very” or “extremely important” to establish SI. Most clinicians (82%) reported using more stringent criteria to establish SI in patients at high risk of a CV event. Respondents estimated that an average of 57% of patients with confirmed SI and at high risk of CV events would continue with lowdose statins, with or without another lipid-lowering therapy (LLT); 30% would receive only a non-statin LLT and 14% no LLT. Most clinicians (67%) reported using Canadian Cardiovascular Society guidelines for lipid management in these patients. Conclusions: Canadian clinicians use several strategies to establish SI and continue LLT in these patients. Only a minority of patients with SI receive no LLT, putting them at high risk of a CV event.
EAS16-0775, PHARMACOLOGY OF DYSLIPIDEMIA. PCSK9 CIRCULATING LEVELS AND CETP PLASMA ACTIVITY ARE ASSOCIATED INDEPENDENTLY OF LIPID LOWERING THERAPIES 2, M. Heras 1, L. J. Girona 1, D. Ibarretxe 1, N. Plana 1, S. Guaita 1, N. Amigo Masana 1. 1 Sant Joan University Hospital, Universitat Rovira i Virgili-IISPV, CIBERDEM, Vascular Medicine and Metabolism Unit-Research Unit on Lipids and Atherosclerosis, Reus, Spain; 2 Universitat Rovira i Virgili-IISPV, Biosfer Teslab, Department of Electronic Engineering, Reus, Spain Objectives: PCSK9 inhibition is a new powerful cholesterol-lowering therapy. Recently, it has been communicate that CETP inhibitors could influence PCSK9 levels as off-target effect. We have explored the relationship of PCSK9 levels and CETP activity in patients with metabolic diseases not on lipid lowering therapy. Methods: Plasma CETP activity and PCSK9 levels were measured in 450 participants (mean age, 58 years; 49% women) who attended the metabolism unit because, metabolic syndrome (MetS) (78%), atherogenic dyslipidemia (32%), obesity (50%), diabetes (72%), and other risk factors (13%) after six week lipid lowering drug wash-out period. Results: Plasma PCSK9 levels and CETP activity were significantly elevated in MetS (12,4%, p¼0,004 and 11,2%, p<0,0001, respectively). Remarkably, plasma PCSK9 levels were positively correlated with CETP activity in whole population (r¼0,256, p<0,0001) independently of age, gender, body mass index (BMI), systolic blood pressure (SBP), triglycerides, LDL-C and glucose. Individuals with the loss-of-function PCSK9 genetic variant rs11591147 (R46L) that have lower levels of PCSK9 (36,5%, p<0,0001) and LDL-C (17,8%, P¼0,010) also was accompanied with lower CETP activity (10,31%, p¼0,009). In multiple regression analysis, this association remained significant even after adjusting for gender, age, BMI, triglycerides, LDL-C, glucose, LCAT, SBP and MetS (p¼0,003). Conclusions: Our data reveal a significant association between PCSK9 and CETP regardless of lipid lowering treatment. This association is maintained in patients with lower PCSK9 genetically determined. The clinical implications of this metabolic relationship could be of interest, explaining in part the effect of PCSK9 and CETP inhibition on overall lipid profile.
EAS16-0488, PHARMACOLOGY OF DYSLIPIDEMIA. UNDERSTANDING LIPOPROTEIN(A) METABOLISM: REBOUND ANALYSES OF LIPOPROTEIN(A) AND PCSK9 CONCENTRATIONS FOLLOWING REGULAR LIPOPROTEIN APHERESIS TREATMENT (THE LIPARE-STUDY) E. Waldmann 1, E.M. Ooi 2, P.H.R. Barrett 2, D.C. Chan 2, S.M. Marcovina 3, G.F. Watts 2, K.G. Parhofer 1. 1 Ludwig-Maximilians-University Munich, Department for internal medicine II, Munich, Germany; 2 University of Western Australia, School of Medicine and Pharmacology,