1. Statin Induce Myotoxicity
นสภ.อัจจิมา บัวหลวงงาม

2. Risk of myotoxicity Lipophilicity>>>hydrophillic
all statins can cause myopathy with a risk of progressing to rhabdomyolysis.
The risk appears to increase with higher doses.
Lipophilicity>>>hydrophillic
lipophilic
Atorvastatin, Fluvastatin, Lovastatin, Simvastatin
hydrophilic
Pravastatin, Rosuvastatin

3. Mechanism HMG-CoA Statins Atrogin-1 mevalonate
HMG-CoA reductase
Statins
mevalonate
antioxidant and membrane stabilizer that is utilized by mitochondria for electron transport
Atrogin-1
ubiquinone (coenzyme Q10)
mitochondrial adenosine triphosphate (ATP)

4. Classification of Muscular Adverse Events
Br J Cardiol,2005

5. Classification of Muscular Adverse Events
Br J Cardiol,2005

6. The American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute (ACC/AHA/NHLBI)
1. Statin myopathy: muscle complaints related to statin drug use
2. Myalgia: muscle complaints without serum CK elevations
3. Myositis: muscle symptoms with serum CK elevations
4. Rhabdomyolysis: markedly elevated CK levels, usually > 10 times ULN, with an elevated creatinine level consistent with pigmentinduced nephropathy
J Am Coll Cardiol. 2002; 40:

7. สารราชวิทยาลัยอายุรแพทย์ฯ
myopathy
มีอาการกล้ามเนื้ออักเสบร่วมกับระดับของ creatine kinase (CK) >10 เท่า ของ ULN
สารราชวิทยาลัยอายุรแพทย์ฯ ปีที่23 ฉบับที่ 3 กรกฎาคม–ธันวาคม 2549

8. The National Lipid Association
rhabdomyolysis
muscle cell destruction or enzyme leakage, regardless of the CK level when measured,
considered to be causally related to a change in renal function
(Thompson et al 2006).

9. The National Lipid Association
Classify absolute CK elevation
Mild: CK increases < 10 times ULN
Moderate: CK increases ≥ 10 times ULN, and
Severe: CK increases ≥ 50 times the ULN
(Thompson et al 2006).

10. Time to onset
Mean duration of thereapy
6.3 months ( months)

11. Incidence Myalgia without changes in CK levels (Bays 2006).
21 statin-based clinical trials with over 180,000 person years for evidence of muscle toxicity.
The incidence of myopathy was 11 per 100,000 person-years.
The incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6–6.5) per 100,000 person-years
10-fold higher when gemfibrozil was used in combination with statins.
For statins metabolized by CYP3A4 such as lovastatin, atorvastatin, and simvastatin), the incidence was 4.2 per 100,000 person-years. In this group, interaction with drugs known to inhibit CYP3A4 (ie, erythromycin and azole antifungals) occurred in 60%

12. The American Journal of Cardiology. Vol 97 (8A) April 17, 2006

13. The American Journal of Cardiology. Vol 97 (8A) April 17, 2006

14. Management

15. Monitor transaminase level
When start Statin or fibrates
After medication 6-12 weeks
Follow up every 1-2 time per year
High dose or more than 2 medication
3-6 months
Guidelines for Management of Dyslipidemia,สารราชวิทยาลัยอายุรแพทย์ฯ 2545

16. National Lipid Association Statin Safety Recommendations
Muscle effects
Pretreatment measurement of CK levels is generally not necessary unless an individual is at high risk
Routine measurements of CK levels are unnecessary in asymptomatic patients.
Counsel patients on the possiblity of muscle discomfort while on statin therapy and the importance of reporting symptoms.
In symptomatic patients, CK levels should be measured.
a. If CK levels 10 times the ULN then statin therapy may be continued or doses reduced with close monitoring of symptoms.
b. If CK levels 10,000 IU/L or above 10 times the ULN, then admit for IV hydration therapy, monitoring of renal
function, and treatment of rhabdomyolysis.
c. Irrespective of CK levels, if muscle symptoms are intolerable, statin therapy should be discontinued with possible
reinstitution of a different agent or lower dose once asymptomatic.
d. If symptoms recur, alternative therapies should be considered.
Vascular Health and Risk Management 2008:4(2)