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Lipid lowering therapies
- past, present and future
Lipid lowering therapies - past, present and future Professor - - PowerPoint PPT Presentation
Lipid lowering therapies - past, present and future Professor - - PowerPoint PPT Presentation
Lipid lowering therapies - past, present and future Professor Mogens Lytken Larsen Aalborg University Hospital, Denmark It began with the population studies! Relationship between total serum cholesterol concentration and stroke risk by
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It began with the population studies!
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Relationship between total serum cholesterol concentration and stroke risk by subtype from MRFIT. From Ansell in Curr Atheroscler Rep 2000.
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Before statins
- Bile acid sequestering resins *
- Neomycin
- Beta-sitosterol
- Nicotinic acid *
- Clofibrate *
- Probucol
- D-thyroxine
* tested in clinical trials
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LRC-CPPT - resins
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Coronary Drug Project - Niacin
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POSCH study – ilial bypass
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LDL lowering today
- Statins (1987)
- Ezetimibe (2002)
- Combinations
- Statin + resins
- Statin + Nicotinic acid
- Statin + ezetimibe
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4S To IDEAL 11 Years Of Landmark Statin Trials
Second Wave Of Trials
- Focus on other high-risk groups
– ACS, elderly, DM, HTN
- Comparisons beyond placebo
– vs usual care (ALLIANCE, ALL-HAT) – active comparator (PROVE IT, A to Z) First 5 Trials Proved RRR In Morbidity And Mortality Vs Placebo 1994 4S 1995 WOSCOPS 1996 CARE 1998 AFCAPS/TexCAPS LIPID 2001 MIRACL 2002 HPS PROSPER ALL-HAT LLT 2003 ASCOT-LLA 2004 PROVE IT ALLIANCE CARDS A to Z 2005 TNT IDEAL Intensity Of Statin Treatment In Stable CHD Patients Receiving Contemporary Therapy
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Relationship Between LDL-C and CV Incidence
Mean Treatment LDL-C at Follow-up, mg/dL (mmol/L) Event, %
30 80 (2.1) 140 (3.6) 200 (5.2) 25 20 15 10 5 100 (2.6) 40 (1.0) 120 (3.1) 180 (4.7)
4S 4S CARE HPS
60 (1.6)
LIPID
Statin Placebo
HPS CARE LIPID
160 (4.1)
PROVE-IT (Atv) PROVE-IT (Pra)
ASCOT
AFCAPS
ASCOT
AFCAPS WOSCOPS WOSCOPS
Secondary Prevention Primary Prevention
IDEAL (Atv) IDEAL (Sim) TNT (Atv 80 mg) TNT (Atv 10 mg)
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AIM-HIGH (N Eng J Med nov. 2011)
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Ezetimibe: LDL-C Lowering Efficacy Regardless of Statin
*Lovastatin, pravastatin, cerivastatin, and fluvastatin Adapted from Gagné C et al Am J Cardiol 2002;90:1084–1091.
–30 –25 –20 –15 –10 –5
Mean % change in calculated LDL-C from on-statin baseline at 8 weeks Simvastatin Atorvastatin Other statins* Statin + placebo Statin + ezetimibe
–26.8 –23.5 –3.1 –3.8 –4 –25
(n=117) (n=123) (n=162) (n=146) (n=111) (n=110)
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1.8 vs. 1.4
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- Bempodoic acid
- CETP inhibitors
- PCSK9 inhibitors
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Three CETP inhibitors failed - # 4 succesfull ???
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NEJM march 17, 2017
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Small interferingRNA – a new PCSK9 approach
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NEJM 2017,376;41-51
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CONCLUSION
- Statins and ezetimibe will reduce cardiovascular events
- The first PCSK9 inhibitor have been shown to reduce
cardiovascular events - more to come ?
- After three failures with CETP inhibitors one succesful
will be presented next week (??)
- What will the future bring ?
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