1. Approaches to the management
of statin intolerant patients
By
Ashraf Reda, MD,FESC
Prof and head of Card. Dep., Menofiya University
President of WGLVR
Chairman of EGYBAC

2. The problem
• 5% -10% side effects with statin
• More patients become statin eligible
• The use of high dosage
• Combination therapy
• Special situations: Pregnancy-Elderly-Children
• Run in phases may underestimate the
problem

3. Higher doses= More adverse effects
“TNT”
Non CV mortality with the high doses need further evaluation
Elevated liver enzymes:1.2% vs 0.2% p<0.001
Rhabdomyolysis 2 cases(80mg) vs 3 cases(10mg)
5461 pts. were excluded in the run in phase

4. IDEAL Trial: Serious Adverse Events
2.2% p<0.001
2%
p<0.001
ALT >3x upper
limit of normal
1.1%
0.97%
%
1%
0.11%
0%
Liver Enzyme Elevation Myalgia
Atorvastatin Simvastatin
Liver enzyme elevation and myalgia (%) Presented at AHA 2005

5. Elevated Liver Enzymes: What to do?
• Less than 1%
• Usually asymptomatic
• Rarely cause Liver failure
• Reversible
• Usually improve with continuing statin or
reducing the dose
• Change to another statin is an option

6. Muscle Symptoms
• Myalgia is the most common (1.5-3.5%)
• Myopathy: Less common (0.05%)
• Rhabdomyolysis: Serious ( 1/10000)

7. Co-Q 10
• May reduce statin induced muscle symptoms
• No large well controlled studies
• Minimal side effects

8. -

9. Populations at risk
• Elderly > 75-80
• Small body mass index
• Hepatic or renal dysfunction
• Concomitant medications
• Large amount of Grapefruit
• Combination lipid lowering therapy

10. Steps to Minimize the Risk of Muscle Toxicity with Fibrate–Statin
Combination Therapy
 Use statin alone for non-HDL-C goals
 Use fish oils or niacin rather than fibrates
 Keep the doses of the statin and fibrate low
 Dose the fibrate in the AM and the statin in the PM
 Avoid in renal impairment
 Discontinue therapy if muscle symptoms are present and
CK is >10 times the upper limit of normal

11. Drug–Drug Interactions with Statins
CYP2C9 CYP3A4
Amlodipine Quinidine
Alprenolol
Diltiazem
Fluvastatin Sildefanil
Hexobarbital Clopidogril Warfarin
N- desmethyldiazepan Protease inhibitors Clarithromycin
Tolbutamide Terbinafine Cyclosporine A
Warfarin Verapamil Erythromycin
Erythtromycine
Ketoconazole
Midazolam
Itraconazole
Nefazodone
Nifedipine Mibefradil
Atorvastatin Simvastatin
Cerivastatin Lovastatin
Adapted form Corsini A et al. Atherosclerosis, 2002; 35–40.

12. If not tolerated what to do?
• DC Statin temporarily to be sure that the Side
effects are statin related
• Re-challenge with a lower dose or change to
other statin
• If multiple statins are not tolerated we can use
less effective
drugs(Resin, Ezetimibe, Niacin, Fibrate)
• More intense Life style change program

13. SOMETIMES STATIN COULDN’T BE
AN APTION

14. Referred because of abnormal lipid profile
• 32 yrs female
• 30 weeks twin pregnancy
• IUF
• +ve FH (CABG for the Father @ 45yrs)
• Father T Cholesterol known to be more than
300 mg/dl
• Border line Bl. G.
• No Ho DM or hypertension

15. Lipid profile
• 1st set : T.Ch: 320mg/dl, TGs: 580onmg/dl
• The day of exam: T ch: 310mg/dl ,TGs: 640
mg/dl

16. Plan
• No statin during pregnancy and lactation
• Fibrates are tumerogenic for the fetous
WHAT TO DO?
• Omega III : safe but no LDL lowering effect
• Glucose-Insulin infusion
• Immunoadsorpton session??

18. New Statin Intolerance Clinic:
Work up
• Validated questionnaire including FH of statin
intolerance
• Level of CK and Vit. D
• Renal and thyroid function tests
• Genetic testing for statin efficacy and
potential toxicity
• Proximal muscle strength evaluation
• Percutaneous muscle biopsy

20. Cardiology@Menofiya
Facebook group
www.cardiolipid.com

21. Conclusions
• Statin intolerance is not common however the
numbers are increasing as Millions are
receiving statin
• Side effects with a statin do not mean that
other statin couldn’t be used
• Elderly, Low BMI, hepatic or renal
dysfunction, high dosage and combinations
are important predictors

22. Immunoadsorption- LDL aphaeresis (to take away
[Greek])
Indications:
*failure medical (>LDL>200 mg/dl with CAD)
and > 300 mg/dl without CAD
*Coast s 3000 / tt every 2 weeks for life

23. Statin in childhood for familial dyslipidemia
• The earlier to start the better (CIMT)
• As early as 8 years is effective and probably
safe

24. Apo A-1 Milano
• Five weekly infusions of an ApoA-I Milano/ phospholipid
complex produced significant regression of coronary
atheroma burden by IVUS.
• Adverse events were similar to placebo.
• Coronary disease is more dynamic than previously
realized and can be rapidly affected by agents that
augment reverse cholesterol transport.
24

25. Another non statin way to do it
APO-A1

26. Characteristics of human
ApoA-IMilano Carriers
Discovered in 1979 Limone sul Garda
•Rare R173C mutation in apoA-I
•Circulates as dimers and monomers
•HDL/apoA-I deficiency
•Mild hypertriglyceridemia
•Paradoxical resistance to heart
“Gain of Function” disease
Mutation 26

28. With LDL 300, TG 520mg/dl start with
1. Fenofibrate
2. statin
3. Statin + Fibrate
4. Statin+ Ezetemib

29. When liver enzymes increase to 1.5
times base line
1. Continue with the same dose
2. Change to another statin
3. Reduce the dose
4. Replace with fibrate

30. All are contraindications to statin
therapy except
1. Pregnancy
2. Lactation
3. Liver cirhosis
4. Active hepatitis

31. All are RF for statin muscle toxicity
except
• Age below 40 yrs
• Renal impairment
• Liver dysfunction
• Combination therapy

32. All can improve statin intolerance
except
• Adding Co Q10
• Giving fibrate @AM and Statin @PM
• Using 2c9 metabolized statin
• Using Cyp3A4 metabolized statin

33. CardioEgypt 2011
1. 16-20 October
2. 17- 21 October
3. 18-22 October
4. 19-23 October