Refractory dyslipoproteinemia         Pr dr M A. BADR        ALEX FAC OF MED              Pr Dr M A BADR
Six Aims for Improvement• Safe – avoiding injuries to patients from the care that is intended to  help them.• Effective – ...
Persistence of Use of Lipid-Lowering      Medications A Cross-National Study        Jerry Avorn, MD; Johanne Monette, MD, ...
Types and Fields of adherence:   (simple or combinations)I- In Medication    - total stop ( of one or more medicines)    -...
II- In Dieting   - unrestricted (exceed total intake)   - errors in caloric distribution , number of meals     snacks, ski...
III- In Exercise:      basal – working – sports .IV- In Other Behaviours:       ( smoking--alcohol –drugs addictions--    ...
Grades of Non adherenceUncompliance :    - Minor and major    - Continuous or interrupted    - Single or multiple aspects
Diagnostic Approach to Uncompliance   A- Patient Factors :1- Psychological state after recent discovery      ( at stages o...
B- Inadequate Education at ManagementI- unclear objectives   Knowledge :,unsuitable,wrong priorities.   Skills : psychomot...
( b)    In teaching skills,         inadequate description--demonstration and exercise . (c) Neglect of attitudes changes ...
How to help patients manage             their dyslipidemia: A primary             care             physician–pharmacist te...
Training of all team members: An 8-hourworkshop was developed to familiarizepharmacistswith:1. The Canadian dyslipidemia t...
Major drugs ineffective for many…Hypertension Drugs 10-30%                  ACE InhibitorsHeart Failure Drugs 15-25%      ...
Quantitative medicine is the key to     reducing healthcare costs and improving              healthcare outcomes          ...
Pharmacogenomics  The study of genome-derived data to predict a  body’s response to a drug or susceptibility to a  disease...
Affymetrix Microarrays             1.28cm50um                 ~107 oligonucleotides,                 half Perfectly Match ...
Affymetrix Microarray Raw                 Image                                          Gene             Value           ...
SNPs• Occur when a single nucleotide (A,T,C,or G) in the  genome sequence is altered, e.g., AAGGCTAA to  ATGGCTAA• Compris...
The influence of SLCO1B1 (OATP1B1)genepolymorphisms on response to statintherapySPR Romaine1, KM Bailey1,AS Hall2 and AJ B...
SNPhepatocytes and recent interest has focused on genetic variation in hepaticinflux and efflux transporters for their pot...
An association study of 43SNPs in 16 candidategenes with atorvastatinresponse ABSTRACT Variation in individual response to...
Pharmacogenomics blames the  patient, NOT the drugs…• Treatment failure• Toxicity• Adverse events
Don’t blame my genes!!!• Make a good drug   New paradigm of research should focus    on molecular targets   Drug structu...
What are effective medication combinations for dyslipidemia?Joseph Saseen, PharmD, FCCP; Elizabeth Tweed   , BSN, MLIS Uni...
LDL - HYPERCHOLEST                               TARGET VALUES NOT                 STATIN                                 ...
HYPERTRIGLICEREDEMIA                LIFE STYLE MODIFICATION       SECONDARY CAUSES; ALCOHOL,DIABETES,OBESITY              ...
COMBINED HYPERLIPOPROT         LIFE STYLE MODIFICATION           STATIN                               POSIBLE COMBINATION ...
Lp(a) hyperlipoproteinemia    OPTIMIZE CARDIOVASCULAR RISK FACTORS                           ATHEROSCLEROSIS      NOATHERO...
DIABETIC   DYSLIPOPROTEINEMIA                GLUCOSE CONTROL     ISOLATED                  COMBINED HLPHYPERTRIGLYCERIDEMI...
Apheresis• What can transfusion medicine offer to  patients with hypercholesterolemia?  Recent advances in affinity column...
Non-HDL Cholesterol(Non-HDL Chol = TC - HDL)• Known predictor of CHD in  epidemiology• Equivalent to total apo B-100, and ...
HMG CoA Reductase    Inhibitors (Statins)Statin           Dose RangeLovastatin        20–80 mgPravastatin       20–40 mgSi...
APHERESIS
APHERESIS
AUTOLOGOUS DELIPIDATED HDL• HDL Therapy Via Plasmapheresis• A First-In-Man, Randomized, Placebo-  Controlled Study to• Eva...
WASHINTON HOSPITAL CENTER• Ron Waksman, MD; Kenneth Kent, MD, PhD;  Augusto Pichard,• MD; William Suddath, MD; Lowell Satl...
Delipidated" HDL• Delipidated" HDL: A new option for plaque  regression?  Other studies have established that increasing  ...
Table: Change in IVUS parameters, Post delipidation treatments minus baseline ACS presentation.
Principle of LDL apheresis• . LDL apheresis works by leading  venous blood through a collumn coated  with antibodies to ap...
Autologous plasma delipidation    using a continuous flow• Autologous plasma delipidation using a continuous flow  system•...
Refractory dyslipedimia
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Refractory dyslipedimia

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Guidelines in refractory dyslipidemia treatment

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  • Qualitative medicine Diagnosis  Standard care Does not work for all
  • Refractory dyslipedimia

    1. 1. Refractory dyslipoproteinemia Pr dr M A. BADR ALEX FAC OF MED Pr Dr M A BADR
    2. 2. Six Aims for Improvement• Safe – avoiding injuries to patients from the care that is intended to help them.• Effective – providing services based on scientific knowledge to all who could benefit and refraining from providing services to those not likely to benefit (avoiding underuse and overuse)• Patient-centered – providing care that is respectful of and responsive to individual patient preferences, needs and values and ensuring that patients values guide all clinical decisions.• Timely – reducing waits and sometimes harmful delays for both those who receive and those who give care.• Efficient – avoiding waste, including waste of equipment, supplies, ideas and energy.• Equitable – providing care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographic location, and socio-economic status.
    3. 3. Persistence of Use of Lipid-Lowering Medications A Cross-National Study Jerry Avorn, MD; Johanne Monette, MD, MSc; Anne Lacour, PhD; Rhonda L. Bohn, MPH; Mark Monane, MD, MS; Helen Mogun, MS; Jacques LeLorier, MD, PhD JAMA. 1998;279:1458-1462. Context.— Although clinical trials have demonstrated the benefits of lipid-lowering therapy, little is known about how these drugs are prescribedConclusion.— In all populations studied, patients who wereprescribed lipid-lowering drug regimens remained withoutfilled prescriptions for over a third of the study year onaverage. Rates of persistence varied substantially with choiceof agent prescribed, comorbidity, and socioeconomic status,despite universal coverage of prescription drug costs. After 5years, about half of the surviving original cohort in theUnited States had stopped using lipid-lowering therapyaltogether.
    4. 4. Types and Fields of adherence: (simple or combinations)I- In Medication - total stop ( of one or more medicines) - diminish or exceed dose - change type - interrupted treatment.
    5. 5. II- In Dieting - unrestricted (exceed total intake) - errors in caloric distribution , number of meals snacks, skip meals, irregular timing ,etc. - Type: Over- intake of Fat , Sugar, etc (salt)
    6. 6. III- In Exercise: basal – working – sports .IV- In Other Behaviours: ( smoking--alcohol –drugs addictions-- contraindicated medications (eg. B Blockers).
    7. 7. Grades of Non adherenceUncompliance : - Minor and major - Continuous or interrupted - Single or multiple aspects
    8. 8. Diagnostic Approach to Uncompliance A- Patient Factors :1- Psychological state after recent discovery ( at stages of denial , revolt , despair ….)2- Having wrong concepts and belief ( health locus , cause of illness , distorted information.)3- Nonspecific totalitarian lovers of opposing stand.4- Slaves of their habits ( e.g. smoking , diet, exercise )5- Transient depression from failing to achieve goals .6- Transient stress : social , economic , inter-current illness.
    9. 9. B- Inadequate Education at ManagementI- unclear objectives Knowledge :,unsuitable,wrong priorities. Skills : psychomotor , communication and cognitive . Attitudes and Behaviors.II- Inadequate methods : (a) In providing knowledge : - Too much , or unsuitable content in a presentation. - Poor performance at the one-to-one education ( listen, motivate, encourage, etc. ). - In small group education: ( ignorance of group dynamics ) - In large group presentation: ( Inability to ensure active participation of audience.) - In mass media education: (inducing panic and confusion). - Inadequate use of AV- aids ,and education facilities .
    10. 10. ( b) In teaching skills, inadequate description--demonstration and exercise . (c) Neglect of attitudes changes through model inspiration (good & bad) , contacts , discussions. etc.III- Absence of follow-up evaluation: - pre and post testing - follow up records of control parameters and compliance - check lists of performance of skills - rating scales for attitude changes
    11. 11. How to help patients manage their dyslipidemia: A primary care physician–pharmacist team intervention Julie Villeneuve, MSc; Diane Lamarre, MSc; Marie-Claude Vanier, MSc; Marie- Thérèse Lussier, MD, MSc; Jacques Genest Jr., MD, FRCP(C); Eveline Hudon, MD, MClSc; Lucie Blais, PhD; Sylvie Perreault, PhD; Lyne Lalonde, PhDC P J / R P C • S E P T E M B E R / OCTO B E R 2 0 0 7 • VOL 1 4 0 , N O 5
    12. 12. Training of all team members: An 8-hourworkshop was developed to familiarizepharmacistswith:1. The Canadian dyslipidemia treatmentrecom -mendations and dyslipidemia pharmacotherapy26,272. The physician-pharmacist teaminterventionand the clinical tools3. The monitoring and interpretation oflaboratorytests4. Adherence intervention strategies Technical tools to facilitate adherence Devices , I phone , reminder…….
    13. 13. Major drugs ineffective for many…Hypertension Drugs 10-30% ACE InhibitorsHeart Failure Drugs 15-25% Beta Blockers Anti Depressants 20-50% SSRIs Cholesterol Drugs 30-70% Statins Asthma Drugs 40-70% Beta-2-agonists Source: Amy Miller, Personalized Medicine Coalition
    14. 14. Quantitative medicine is the key to reducing healthcare costs and improving healthcare outcomes Non-responders, toxic respondersPatients with same diagnosis Non-toxic responders Misdiagnosed
    15. 15. Pharmacogenomics The study of genome-derived data to predict a body’s response to a drug or susceptibility to a disease:• Human genetic variation in DNA – Single nucleotide polymorphisms (SNPs) – Copy number differences – Insertions – Deletions – Duplications – Rearrangements• RNA and protein expression differences
    16. 16. Affymetrix Microarrays 1.28cm50um ~107 oligonucleotides, half Perfectly Match mRNA (PM), half have one Mismatch (MM) Gene expression computed from PM and MM
    17. 17. Affymetrix Microarray Raw Image Gene Value D26528_at 193 D26561_cds1_at -70 D26561_cds2_at 144 D26561_cds3_at 33 D26579_at 318 D26598_at 1764 D26599_at 1537 D26600_at 1204 D28114_at 707 Scanner raw dataenlarged section of raw image
    18. 18. SNPs• Occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered, e.g., AAGGCTAA to ATGGCTAA• Comprise 90% of all human genetic variation• Exist every 100 to 300 bases along the 3-billion-base human genome• Found in both coding (i.e., gene) and noncoding regions of the genome.• Usually have no effect on cell function, but some could predispose people to disease or influence their response to a drug
    19. 19. The influence of SLCO1B1 (OATP1B1)genepolymorphisms on response to statintherapySPR Romaine1, KM Bailey1,AS Hall2 and AJ Balmforth11Division of Cardiovascular and DiabetesResearch, Leeds Institute of Genetics, Health andTherapeutics, University of Leeds, Leeds, UK and2Multidisciplinary Cardiovascular ResearchCentre (MCRC), Leeds Institute of Genetics,Health and Therapeutics, University of Leeds,Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) arewell established in the treatment of hypercholesterolaemia and theprevention of coronary artery disease.
    20. 20. SNPhepatocytes and recent interest has focused on genetic variation in hepaticinflux and efflux transporters for their potential to explain these differences.In this review we explore current literature regarding the pharmacokineticand pharmacodynamic influence of the common c.388A4G and c.521T4Csingle-nucleotide polymorphisms (SNPs) within the solute carrier organicanion transporter 1B1 (SLCO1B1) gene, encoding the organic aniontransporter polypeptide 1B1 (OATP1B1) influx transporter. We discuss theirpotential to predict the efficacy of statin therapy and the likelihood thatpatients will experience adverse effects.The Pharmacogenomics Journal (2010)
    21. 21. An association study of 43SNPs in 16 candidategenes with atorvastatinresponse ABSTRACT Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. The Pharmacogenomics Journal (2005) 5, 352–358 & 2005 Nature Publishing Group All rights reserved 1470-269X/05 $30.00 www.nature.com/tpj
    22. 22. Pharmacogenomics blames the patient, NOT the drugs…• Treatment failure• Toxicity• Adverse events
    23. 23. Don’t blame my genes!!!• Make a good drug New paradigm of research should focus on molecular targets Drug structure• Focus on lifestyle changes• Therapeutic drug monitoring• Patient counseling, error reporting• Increase healthcare availability first
    24. 24. What are effective medication combinations for dyslipidemia?Joseph Saseen, PharmD, FCCP; Elizabeth Tweed , BSN, MLIS University of Colorado at Denver and Health Sciences
    25. 25. LDL - HYPERCHOLEST TARGET VALUES NOT STATIN ACHIEVED NOT COMBINATION WITH TOLERATED EZETIMIBE TARGETACHIEVED AND TOLERATED EZETEMIBE ADDITITIONAL BILE ACID BINDING BILE ACID BINDING RESIN LDL-APHERESIS FIBRATE/ CAD NIACIN
    26. 26. HYPERTRIGLICEREDEMIA LIFE STYLE MODIFICATION SECONDARY CAUSES; ALCOHOL,DIABETES,OBESITY FIBRATE TARGET VALUES NOT ACHIEVED TARGET VALUES NOT ACHIEVED TOLERATED AND WELLTOLERATED CONSIDER STATIN COMBINATION WITH NIACIN NIACIN
    27. 27. COMBINED HYPERLIPOPROT LIFE STYLE MODIFICATION STATIN POSIBLE COMBINATION STATIN WITH NICOTINIC TARGET NOT ACHIEVED FIBRATE WITHG NICOTINIC FIBRATE FIBRATE WITH EZETIMIBE AND STATIN WITH FIBRATE
    28. 28. Lp(a) hyperlipoproteinemia OPTIMIZE CARDIOVASCULAR RISK FACTORS ATHEROSCLEROSIS NOATHEROSCLEROSIS STATIN COMBINATION STATIN WITH NIACIN CAD WORSEN CONSIDER APHERESIS
    29. 29. DIABETIC DYSLIPOPROTEINEMIA GLUCOSE CONTROL ISOLATED COMBINED HLPHYPERTRIGLYCERIDEMIA LDL-HYPERCHOLEST STATIN FIBRATE TARGET NOT ACHIEVED INCREASE STATIN + STATIN + STATIN+ STATIN EZETEMIBE NIACIN fibrate
    30. 30. Apheresis• What can transfusion medicine offer to patients with hypercholesterolemia? Recent advances in affinity column technology now enable the efficient removal of LDL-cholesterol directly from the bloodstream by apheresis. This new therapeutic tool may reduce the risk of progressive atherosclerotic disease in hypercholesterolemic patients who are resistant to diet and drugs
    31. 31. Non-HDL Cholesterol(Non-HDL Chol = TC - HDL)• Known predictor of CHD in epidemiology• Equivalent to total apo B-100, and TC/HDL• Represents the sum of LDL, Lp(a), IDL, and VLDL: All atherogenic apo B containing lipoproteins• Accounts for 50% of the CHD risk reduction provided by HDL
    32. 32. HMG CoA Reductase Inhibitors (Statins)Statin Dose RangeLovastatin 20–80 mgPravastatin 20–40 mgSimvastatin 20–80 mgFluvastatin 20–80 mgAtorvastatin 10–80 mgCerivastatin 0.4–0.8 mg
    33. 33. APHERESIS
    34. 34. APHERESIS
    35. 35. AUTOLOGOUS DELIPIDATED HDL• HDL Therapy Via Plasmapheresis• A First-In-Man, Randomized, Placebo- Controlled Study to• Evaluate the Safety• and Feasibility of Autologous Delipidated HDL Plasma Infusions• in Patients with Acute Coronary Syndrome
    36. 36. WASHINTON HOSPITAL CENTER• Ron Waksman, MD; Kenneth Kent, MD, PhD; Augusto Pichard,• MD; William Suddath, MD; Lowell Satler, MD; Dianne Martin,• RN; Timothy Perlman; Dale Richardson, MBA; Jo-Ann Maltais,• PhD; Patricia Landry, MBA; Rebecca Torguson, MPH; Neil J.• Weissman, MD; Peter Fitzgerald, MD; H. Bryan Brewer, MD
    37. 37. Delipidated" HDL• Delipidated" HDL: A new option for plaque regression? Other studies have established that increasing pre-beta HDL increases cholesterol efflux and that pre-beta HDL is the most effective form of HDL for lipid removal from arterial plaque via reverse cholesterol transport. Plasma delipidation, through apheresis, converts alpha HDL to pre-beta HDL and in theory may lead to regression of atherosclerosis
    38. 38. Table: Change in IVUS parameters, Post delipidation treatments minus baseline ACS presentation.
    39. 39. Principle of LDL apheresis• . LDL apheresis works by leading venous blood through a collumn coated with antibodies to apolipoprotein B (the main protein of LDL particles), dextran sulphate or polyacrylate , or by precipitating LDL with heparin at low pH
    40. 40. Autologous plasma delipidation using a continuous flow• Autologous plasma delipidation using a continuous flow system• United States Patent 4895558• A method and apparatus for autologous plasma delipidation of animals (including humans). The method comprises drawing blood from the animal, separating the plasma from the red blood cells, delipidating the plasma with a lipid solvent, remixing the delipidated with the red blood cells and re-introducing the delipidated blood into the animal. A preferred apparatus which utilizes the above method comprises a needle for drawing blood from the animal and the blood is then fed into a centrifugal separator where the blood is separated into the plasma and red blood cells. The plasma is then mixed with a biphase solvent and passed through a separator where the delipidated plasma (in an aqueous phase) is drawn off from the lipid components (in an organic phase). After removal of solvent, the delipidated plasma is remixed with the red blood cells and re- introduced to the animal by a re-infusion needle.
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