Statin intolerant patients

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  • 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 evaluationElevated liver enzymes:1.2% vs 0.2% p<0.001Rhabdomyolysis 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 LovastatinAdapted 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 BEAN 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??
  • 17. 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
  • 18. Cardiology@Menofiya Facebook groupwww.cardiolipid.com
  • 19. 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
  • 20. 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
  • 21. Statin in childhood for familial dyslipidemia• The earlier to start the better (CIMT)• As early as 8 years is effective and probably safe
  • 22. 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
  • 23. Another non statin way to do itAPO-A1
  • 24. Characteristics of humanApoA-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
  • 25. With LDL 300, TG 520mg/dl start with1. Fenofibrate2. statin3. Statin + Fibrate4. Statin+ Ezetemib
  • 26. When liver enzymes increase to 1.5 times base line1. Continue with the same dose2. Change to another statin3. Reduce the dose4. Replace with fibrate
  • 27. All are contraindications to statin therapy except1. Pregnancy2. Lactation3. Liver cirhosis4. Active hepatitis
  • 28. All are RF for statin muscle toxicity except• Age below 40 yrs• Renal impairment• Liver dysfunction• Combination therapy
  • 29. All can improve statin intolerance except• Adding Co Q10• Giving fibrate @AM and Statin @PM• Using 2c9 metabolized statin• Using Cyp3A4 metabolized statin
  • 30. CardioEgypt 20111. 16-20 October2. 17- 21 October3. 18-22 October4. 19-23 October