What are the common side effects of statins (HMG-CoA reductase inhibitors)?

Common Side Effects of Statins

The most common side effects of statins are muscle-related symptoms (occurring in 5-10% of patients in observational studies), followed by modest increases in the risk of new-onset diabetes mellitus in susceptible individuals, and infrequent liver enzyme elevations. 1

Muscle-Related Side Effects

Statin-associated muscle symptoms (SAMS) represent the most frequently reported adverse effects:

• Myalgia (muscle pain/aches):

  • Occurs in 1-5% of patients in randomized controlled trials and 5-10% in observational studies 1
  • More likely to be statin-related if bilateral, involves proximal muscles, begins within weeks to months of starting therapy, and resolves after discontinuation 1
  • Usually not associated with significant creatine kinase (CK) elevations 1

• Predisposing factors for SAMS:

  • Age, female sex, low body mass index
  • High-risk medications (CYP3A4 inhibitors, OATP1B1 inhibitors)
  • Comorbidities (HIV, renal/liver/thyroid disease, pre-existing myopathy)
  • Asian ancestry, excess alcohol, high levels of physical activity, trauma 1

• Severe muscle effects (rare):

  • Myositis/myopathy: Muscle symptoms with CK elevation above upper limit of normal
  • Rhabdomyolysis: CK >10x upper limit of normal with renal injury (exceedingly rare)
  • Statin-associated autoimmune myopathy: Characterized by muscle weakness, marked CK elevation, presence of HMGCR antibodies, and incomplete resolution after statin discontinuation 1

Metabolic Effects

• New-onset diabetes mellitus:
  • Modest increase in risk, particularly in individuals with pre-existing risk factors 1
  • More frequent with higher-intensity statin therapy 1
  • Risk factors include: BMI ≥30, fasting blood glucose ≥100 mg/dL, metabolic syndrome, A1c ≥6% 1
  • Despite this risk, benefits of statin therapy outweigh the risk of diabetes, and statins should not be discontinued solely for this reason 1

Liver Effects

• Transaminase elevations:
  • Occur in 0.5-2.0% of patients and are dose-dependent 1
  • Asymptomatic elevations >3x upper limit of normal are infrequent 1
  • Often resolve with dose reduction or alternative statin 1
  • Severe hepatotoxicity is extremely rare 1, 2

Other Reported Side Effects

• Central nervous system effects:

  • Memory/cognitive issues: Rare, generally reversible upon discontinuation 3, 4
  • Dizziness, depression, peripheral neuropathy (rare) 3, 4

• Dermatologic reactions:

  • Rash, eczema, pruritus (uncommon) 3, 4

• Gastrointestinal symptoms:

  • Abdominal pain, constipation (reported in 2-6% of patients) 3, 4

Management of Statin Side Effects

1. For muscle symptoms:

   • Measure CK in patients with severe symptoms or objective weakness 1
   • Consider temporary discontinuation until symptoms improve 1
   • Rechallenge with lower dose, alternative statin, or alternative dosing regimen 1

2. For diabetes risk:

   • Continue statin therapy despite increased risk 1
   • Emphasize lifestyle modifications (regular physical activity, healthy diet, modest weight loss) 1

3. For liver enzyme elevations:

   • Routine monitoring of transaminases is not recommended 1
   • Measure liver enzymes if symptoms of hepatotoxicity develop 1
   • For persistent significant elevations, evaluate for non-statin causes 1

Important Caveats

• Many reported muscle symptoms may be non-specific and not directly related to statin therapy, as similar rates occur in placebo groups 1
• Coenzyme Q10 supplementation is not recommended for routine use in patients on statins or for treatment of SAMS 1
• The "reassess, rediscuss, and rechallenge" approach allows most patients with initial statin-associated side effects to successfully continue some form of statin therapy 1
• Several reported side effects (renal function changes, cataracts, tendon rupture, hemorrhagic stroke, interstitial lung disease, low testosterone) have unfounded associations with statin use 1

The decision to continue statin therapy should always weigh the cardiovascular benefits against the potential side effects, with the understanding that for most patients at increased cardiovascular risk, the benefits substantially outweigh the risks.