Dyslipidemia Management in 2016 Michael Heffernan MD PhD FRCPC FACC Faculty/Presenter  Disclosure   •  Faculty:  Dr  Michael  Heffernan   •  Title  of  Talk:  2016  Dyslipidemia  Update   •  Relationships  with  commercial  interests:   •  Grants/Research  Support:  Bayer,  Boehringer  Ingelheim,   Esai,  AstraZeneca   •  Speakers  Bureau/Honoraria:  AstraZeneca,  Bayer,   Boehringer  Ingelheim,  Bristol  Myers  Squibb,  Pfizer,  Amgen,   Servier,  Sanofi   •  Consulting  Fees:  Bayer,  AstraZeneca,  Boehringer   Ingelheim,  Amgen,  Sanofi   •  Other:  None   Objectives   At  the  end  of  this  presentation,  the  participant  will  be  able   to:     Identify patients not at LDL-C goal despite current treatment and discuss why they would benefit from further LDL-C reduction   Appraise clinical data and new treatment strategies to lower LDL-C in the high risk patient   Discuss clinical management of the high risk patient not at goal and implementation of new treatment strategies The Case: John   56y  male     HTN,  dyslipidemia     Previous  MI  and  angioplasty   at  age  48y     Family  history  of  premature   CAD     Non-­‐smoker     Exercises  100  min/week     ALended  cardiac  rehab  and   adheres  to  dietary  guidelines   The Case   Medica'ons   −  ASA  81  mg  once  daily     −  AtorvastaOn  20  mg   −  Bisoprolol  5  mg  once  daily   −  Ramipril  10  mg  once  daily     Lipid  Profile   −  TC:  5.9  mmol/L   −  TG:1.4  mmol/L     −  HDL-­‐C:  1.4  mmol/L   −  LDL-­‐C:  3.6  mmol/L  (current)   −  non-­‐HDL-­‐C:  4.3  mmol/L     −  He  has  tried  rosuvastaOn  but  was  unable  to  tolerate  it  (mylagias)   −  He  was  on  40  mg  of  atorvastaOn  however  this  also  provoked  myalgias   −  He  can  tolerate  20  mg  of  atorvastaOn   What is John’s Target and Why Do We Want to Get Him There ? The Cholesterol Hypothesis Originated with Observational Studies Epidemiologic Data – Serum Cholesterol Levels and CHD MRFIT trial: age-adjusted CHD death rate and serum cholesterol in 361,662 US men (aged 35–57 years) Each 1% Increase in Total Cholesterol Level is associated with a 2% Increase in CHD Risk Martin MJ, et al Lancet 1986;2:933–936 Clinical Trials Validated The LDL Hypothesis 30 These trials have demonstrated that LDL-C lowering is associated with greater reduction of CHD events CHD Event Rate,% 25 Secondary Prevention 4S-P 20 4S-T 15 1O DIABETES PREVENTION Care-P Care-T 10 HPS-T PROS-T TNT-80 TNT-10 Ascot-T JUP-T 1.3 1.8 Lipid-T HPS-P PROS-P WPS-P AFCAPS-P CARDS-T Lipid-P 2.5 Primary Prevention JUP-P AFCAPS-T WPS-T Ascot-P 3.0 3.5 4.0 LDL-C mmol/L 4.5 5.0 5.4 @>4'(.:(24'$*2(&:%(8:$*2/&'/.:.[$Y@**Z$@4''&M42&O48T$V&8G(:T$PIHI\X]"SH"]ICH"5 years Additional populations ODYSSEY CHOICE II Patients with hypercholesterolemia on non-statin LMT or diet N=200; months ODYSSEY OPTIONS I Patients not at goal with moderate dose atorvastatin N=355; months ODYSSEY OPTIONS II Patients not at goal with moderate dose rosuvastatin N=305; months Interesting Concept, But Will It Help John ? OSLER: Evolocumab Plus Standard of Care Achieved a 61% Reduction in LDL-C over Standard of Care at 12 Weeks 3.6 3.1 mmol/L 3.1 2.6 61% reduction (95%CI 59-63%), P,$+48C?&:&'$67,$=&:&'$&8-$848C?&:&'$/.G>(%/G$.:24D(,$p8.:&M'($ &89/8&$2(i5/2/89$>4.0/:&'/d&O48T$VV*,$'/0/-C'4K(2/89$:>(2&0#$ † q$!P$K((D.$?42$&''$0&O(8:.$G48O85/89$:2(&:%(8:,$/8G'T$"I]$0&O(8:.$K>4$G4%0'(:(-$o](&2:$-/.(&.(T$^A6AT$HU]!\PXHY;ZSX"IcX($V/0/-$R(.(&2G>$@'/8/G.$@4248&2#$12/%&2#$12(3(8O48$*2/&'$2(.5':.T$^A6A$ HU[...]... NOT at LDL-C target1* ($ 2 mmol/L) !! 88% of patients received a ‘potent’ statin with suboptimal dose !! 14% of patients received additional lipid- lowering agent 43% Canadian patients with diabetes are NOT at LDL-C target2† ($ 2 mmol/L) !! 82% of patients were on a lipid- lowering agent g)/9>$2/.D$k$ g)/9>$2/.D$k$,./.#+/0!+/-(/0!)12(+2(3!4(/145(/+%!+/-(/1+%!)12(+2(3!,(/(6/.7+2,8%+/!)12(+2(3!)1+6(-(2!9(%%1-82!./!:/+91#$5+9!;!2,./(!?@ 5.0 mmol/L #!Familial hypercholesterolemia !50% reduction in LDL-C Alternate Target #!LDL-C > 3.5 mmol/L... from Jones P, et al for the CURVES Investigators Am J Cardiol 1998;81:582-587 Add-On Therapy has had Moderate Benefit in Further Lowering LDL-C Add-On Therapy$ LDL-C Lowering+ Niacin4-6$ 20% + Other Lipid Effects+ Outcome Data (Add-on to statin)+ " HDL by 30% # TG by 40%$ No benefit as addon to statin7,8$ " HDL-C (10-50%) # TG (20-50%) No benefit as add-on to statin$ Fibrates9,10$ 5 – 20%+ Bile Acid... (%) 50 40 Ezetimibe Fibrate Bile acid resin 30 Niacin Diet/unsat Fatty acid 20 Ileal bypass CTTC trials (statin) 10 IMPROVE-IT 0 0.3 0.5 0.8 1.0 1.3 1.5 Reduction in LDL-C (mmol/L) 1.8 2.1 Non-statin lipid- lowering studies suggest coronary event reduction is due to LDL-C reduction, independent of method @>4'(.:(24'$*2(&:%(8:$*2/&'/.:.[$@4''&M42&O48T$V&8G(:T$PII!\X""SHP"]CHP]($@4248&2#$B259$124b(G:$R(.(&2G>$W2450T$^A6AT$HU]!\PXHSX"IcX