Endocrinology‎ > ‎

Statin Intolerant patients

The "statin" class of medications are excellent drugs to reduce the risk of heart attack. These medication can have some side effects, most commonly muscular aches. Addressing these symptoms are important.


Muscle side effects 

The most common side effect that patients will notice with taking statin medications for cholesterol include
  • Myalgia
    • muscle ache or weakness without creatine kinase (CK) elevation
  • Myopathy
    • myalgia plus elevation in serum CK more than 10 times the upper limit of normal
  • Rhabdomyolysis
    • CK >10 times the upper limit of normal plus an elevation in serum creatinine or medical intervention with IV hydration, or
    • CK >10,000 IU/L


Incidence of muscle adverse events in clinical trials show there are low rates of events. This study reviewed 180,000 very healthy patients patients in 21 major trials for an average of three years. Most muscle side effects are not major life threatening effects. Generally it is muscle aches that resolve with time. 
 Muscle adverse event     Incidence
 Myalgias 1.5 - 3.0%
 Myopathy 5/100,000
 Rhabdomyolysis 1.6/100,000

The PRIMO study showed that the incidence of muscle symptoms was higher overall (10.5%) because the study included all types of patients (using other drugs that use the liver P450 system, drinking alcohol) and not just healthy volunteers. 
 Statin
 % patients with muscle complaints
(n=832)
 Pravastatin 40mg     10.9
 Atorvastatin 40-80mg 14.9
 Simvastatin 40-80mg 18.1
 Fluvastatin XL 80mg 5.1        
 TOTAL % of patients reporting symptoms 10.5%


Risk factors for statin myopathy

There are a number of risk factors for statin myopathy.  Myopathy is most related to the dose of that statin given; the higher the dose the more likely these may be a side effect.  The hydrophilicity of the statin medication and the metabolism of the statin can contribute to the incidence of muscle pains. Statins are are metabolized through the liver's cytochrome P450 system so if other drugs that require the use of this same system can lead to increased effective dose of statin in the blood. Itis not the amount of LDL drop that determines if a patient will have a statin side effect. Hydrophilicity is a physical property of the medication which reflect the ability of the statin to cross water. The most water soluble statins are fluvastatin and pravastatin but they are less efficacious at reducing the LDL. This is a theoretical concern. 

Exercise or increased physical activity- running , jogging, etc can lead to generalized aches unrelated to the statin
Trauma
Alcohol comsumption and drug abuse (cocaine and amphetamines)
Hypothyroidism
Renal disease- 
Baseline muscle disease (inherited metabolic muscle disease)
Increase in age




Monitoring  and Surveillance of statins

  1. Routine CK levels in asymptomatic patient is not recommended
  2. Baseline CK only in patients at increased risk of myopathy
  3. CK levels should be monitored in symptomatic patients
  4. If symptomatic, rule out other etioligies of muscle symptoms or asymptomatic CK elevations (increased physical activity, hypothyroidism, trauma, falls, seizures, etc)
  5. In patients with tolerable muscle symptoms and CK < 5x the upper limit of normal, statin can be continued
  6. Statins should be stopped if the symptoms are intolerable


Management of statin myalgia

Low dose of long acting statins 5mg/day or alternate-day dosing 
Hydrophilic statins (theoretical concerns)- water soluble statins might have less muscle effects- rousevastatin, pravastatin, fluvastatin
Fluvastatin XL (withour without ezetimbe)
Non statin therapy with bile acid sequestrants or niacin
Soluble fiber
Vitamin D supplmental (anecdotal)
Coenzyme Q -unproven but anecdotally helpful
Red yeast rice- contains very low dose lovastatin


References:
Law M et al. Am J of Cardiology. 2006; 97 P 52C
Bruckert et al. Cardiovascular Drugs and Therapy. 2005. 19:403-414
Jacobson TA. Am J Cardiol. 2006. 97; 544-551
Comments