Managing Lipids To Target:

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• Managing Lipids To Target
• The Practicalities
• Dr Susan Connolly
• Consultant Cardiologist
• Imperial College Healthcare NHS Trust
• 22nd April 2009

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4 KEY AREAS

• 1. Understand effects of lifestyle modification
  on lipids
• Be able to anticipate effect of medication that
  you prescribe
• 3. Have a command of switching/uptitration/combina
  tion strategies
• 4. NB know how to handle SFX

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Lifestyle Modification
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Lifestyle Modification

• Coffee
• Dietary cholesterol (e.g. eggs)
• Red yeast
• Nuts
• Stanol/sterol esters

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Stanol
Stanol/sterol esters reduce serum total and LDL
cholesterol concentrations 10-15 Same
reduction seen even with concomitant statin
use No significant change in HDL/triglycerides
Sterol
Sterol
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Lifestyle plateau effect
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Secondary Dyslipidaemia (usually mixed
dyslipidemia)

• Common
• Diabetes NB (normal LDL, low HDL, high TG)
• Alcohol ? TG, HDL
• Drugs (thiazides, bblockers, steroids, phenytoin)
• Obesity
• Hypothyroidism ? TC, LDL

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Primary Dyslipidemia

• Many different
• Two commonest in clinical practice
• 1. Familial combined hyperlipidemia (? TC/?TG or
  both FHx premature CVD)
• 2. FHx think if if TC gt7.5 mmol/L or LDL-C gt4.9
  mmol/L, presence of tendon xanthomata, family
  history of premature CVD
• NB Refer lipid clinic

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Achieving Lipid Control

• Used to be easier when 5 and 3 but 4 and 2
  harder to achieve
• Statin switching
• Uptitration - 6 rule
• Combination therapy e.g. ezetimibe,
  sterols/stannols, colveselam, niacin

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LDL lowering potencies of statins Stellar
Jones at al, Am J Card 200392152-160. Curves
Jones et al, Am J card 199881582-587
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If not achieving target

• Consider compliance
• Dietary indiscretion not as relevant as in BP
• Uptitration 6 rule for every doubling statin
  dose there is a further 6 LDL-C reduction
• If significantly above target by gt0.5 mmol/L, may
  be better to switch to more potent statin
• Or use combination therapy

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Ezetimibe TA 132
Background LDL hypothesis is proven Efficacy Adds
23 LDL-C reduction to all statins or in
monotherapy Utility Use as add-on to statin Use
in monotherapy when statin intolerant Intolerance
includes myalgia as well as myositis More cost
effective than switch/titrate
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Enhance
Mean LDL over 24 month period
Mean CIMT over 24 month period
Simvastatin 80 mg P versus simva 80 mg
ezetimibe 10 mg in patients with FH 325 patients,
mean age 45
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Does ezetimibe have any effect?

• Is CIMT an effective surrogate for CV events?
• 80 pretreated with statins LDL leeched from
  plaque?

ACC use more potent statins to get to target
ezetimibe 3rd line
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SEAS NEJM 2008

• 1873 patients
• Mild to moderate asx AS
• 40 mg simva ezetimibe or placebo
• Median FU 52.2 months
• No sig difference in 1o outcome (Major CV events)

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SEAS NEJM 2008

• 1873 patients
• Mild to moderate asx AS
• 40 mg simva ezetimibe or placebo
• Median FU 52.2 months
• No sig difference in 1o outcome (Major CV events)

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SEAS principal results
Lipids
Events
Change ()
5.74
1.42
1.50
3.60
p0.01
P0.73
P0.97
p0.02
Rossebo AB et al NEJM 2008 359 1343
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N Engl J Med 20083591357-66.
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Colesevelam

• Nonsystemic lipid-lowering agent
• Increases both faecal elimination of bile acids
  and the conversion of cholesterol to bile acids
• Decreases LDL cholesterol levels by 15-18
• Well tolerated unlike BAS of old (but 6 tablets
  per day)
• Combined with ezetimibe, 30 LDL-lowering
  (think of for truly statin intolerant)

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EZETIMIBE SIMVA VERSUS MONOTHERAPY VYVA Study.
Ballantyne. AHJ 2005149464-473
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Liver safety (1)

• Small percentage ?transaminases (lt1)
• Higher in intensive statin group
• Generally in first 6/12 and asx
• Reverse with stopping
• Risk of liver failure probably not above
  background risk
• Caution in labelling someone as statin intolerant
  i.e. benefitgtrisk

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Liver safety (2)

• SPI does recommend baseline measurement LFTs and
  CI in active liver disease
• SPI recommends LFT monitoring in higher dose
  despite lack of evidence on adverse outcome
• If LFTs abnormal but stable and no active liver
  disease, may be reasonable to start statin and
  monitor
• May improve LFTs e.g. NASH

Recommended reading Safety of Statins in
Clinical Practice. Armitage. Lancet
20073701781-90
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Muscle SFX Statins

• Myalgia Muscle ache with normal CK and no
  weakness. Typically affects the larger muscle
  bulks in arms and legs. NB rule out other causes
  of pain, e.g. osteoarthritic joints or
  degenerative back disease
• Myopathy muscle symptoms/weakness CKgt10XULN.
• Rare lt0.01
• Rhabdolysis (muscle symptoms CKgt40XULN). Even
  rarer. NB Usually reported when interacting drugs
  used

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Muscle SFX Statins

• Those more vulnerable to muscle side effects
  include
• the elderly,
• patients with renal failure or hypothyroidism,
• Concomitant use cytochrome P450 inhibitors
  (atorva, simva metabolised via CYP P450 3A4) e.g.
  erythro/clarithromycin, antifungals, protease
  inhibitor, antidepressants, grapefruit juice,
  dilt/verap/amio weak
• Fluva CYP 2C9
• Prava, rosuva - not

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What to do if muscle ache

• 1. Take good history
• 2. Measure CK
• 3. If CK normal stop for 1/52. Do symptoms go
  away? If YES, try weaker dose of same statin
  (i.e. rechallenge)
• 4. If CK high, stop statin immediately. Monitor
  CK. Refer for specialist advice. Usually
  reintroduce statin lower dose as well and
  carefully monitor

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Statin Muscle SFX

• Remember usually dose related
• Try
• Simvastatin 10 mg (still 30 LDL lowering)
• If still symtpoms, try weaker statin e.g. fluva
  20 or prava 10 or rosuva 5 mg alt days
• Some evidence for concomitant use CoQ10

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Key facts medication adherence

• 1. Adherence is dynamic (e.g. improves around
  time of clinic visit)
• 2. Self-report may be inaccurate (difficulties
  with recall, attempts to please healthcare
  provider etc)
• 3. Physician adherence
• Overestimate adherence
• Good at detecting good adherence but not at
  partial or non-adherence)
• Estimated 9-37 patients inadequate adherence
• After one year, up to 50 may have d/c their meds.

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Reasons for poor medication-taking behaviour

• Cost
• Unclear instructions
• Lack of education
• Lack of involvement of patient in plan
• Side effects
• Complexity

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LDL lowering potencies of statins Stellar
Jones at al, Am J Card 200392152-160. Curves
Jones et al, Am J card 199881582-587
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Case 1

• 64 yo man, PPCI to LAD
• Smoking, BP 123/74 mm Hg
• D/C on simvastatin 40 mg
• TC5.5, HDL 0.7, LDL 4.3, TG 1.1
• What to do?

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Case 2

• 71 yo woman, recent ex smoker, BP 162/93, no
  diabetes, TC 7.4, HDL, 2.2, TG 1.1, LDL 4.9

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Case 3

• 36 yo man
• Asymptomatic
• Smoker
• TC 14.5, LDL of 11.49, TG 3.3, HDL of 1.5
• Fasting glucose 4.6 mmol/L
• BMI 27 kg/m2, WC 95 cm
• Mother CABG at 55

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Case 4

• 64 yo man
• AAA repair 4/52 ago
• On simvastatin 40 mg od
• TC 1.8, HDL 0.5, LDL 08., TG 1.1

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Case 5

• 58 yo woman, PCI for angina
• ex cigs, BP 138/84 mm Hg
• TC 4.5, HDL 0.6, LDL 1.9 , TG 4.4