What to do if a patient experiences chills after starting a statin (HMG-CoA reductase inhibitor)?

Management of Chills After Starting Statin Therapy

When a patient experiences chills after starting statin therapy, temporarily discontinue the statin until symptoms resolve, then rechallenge with a lower dose of the same statin or an alternative statin to establish causality. 1

Initial Assessment

1. Evaluate for statin-associated symptoms:

   • Assess timing of chills in relation to statin initiation (typically within weeks to months) 1
   • Document other associated symptoms:
     • Muscle soreness, tenderness, or pain (common statin side effects) 1
     • Flu-like symptoms (weakness, exhaustion, aching muscles/joints) 2
     • Possible fever or subfebrile temperature 2

2. Rule out alternative causes:

   • Check for signs of infection
   • Evaluate for other conditions that increase risk of muscle symptoms 1:
     • Hypothyroidism (measure TSH)
     • Reduced renal or hepatic function
     • Rheumatologic disorders
     • Vitamin D deficiency
     • Primary muscle diseases

3. Laboratory assessment:

   • Measure creatine kinase (CK) levels 1
   • Check liver function tests (ALT/AST)
   • Consider inflammatory markers (if flu-like symptoms present) 2

Management Algorithm

Step 1: Immediate Action

• Temporarily discontinue statin therapy if chills are bothersome or accompanied by muscle symptoms 1
• Document symptoms thoroughly for future reference 1

Step 2: Monitor for Resolution

• Follow the patient until chills and any other symptoms resolve 1
• This typically occurs within 2-4 weeks after discontinuation 1, 3

Step 3: Rechallenge Strategy

• Once symptoms completely resolve, establish causality through rechallenge 1:

  Option A - Same Statin at Lower Dose:

  • Restart the original statin at a lower dose 1
  • Monitor for recurrence of symptoms

  Option B - Alternative Statin:

  • Switch to a different statin with potentially lower risk of side effects 3
  • Consider fluvastatin or pravastatin which may have different tissue selectivity 4

  Option C - Alternative Dosing Regimen:

  • Try alternate-day dosing or twice-weekly dosing 3
  • This maintains some lipid-lowering effect while reducing side effects

Step 4: Long-term Management

• If rechallenge is successful without symptom recurrence:

  • Gradually increase the dose as tolerated 1
  • Monitor periodically for symptoms

• If symptoms recur with rechallenge:

  • Try another statin at low dose 1
  • Consider adding ezetimibe to a lower statin dose to maintain LDL-lowering efficacy 3
  • In high-risk patients who cannot tolerate statins, consider PCSK9 inhibitors 3

Special Considerations

• High-risk patients: For patients at high ASCVD risk, the goal should be to treat with the maximally tolerated statin dose due to mortality benefit 1

• Nocebo effect: Be aware that up to 90% of muscle symptoms may be attributable to expectation of side effects rather than the statin itself 3, 5

• Risk factors for increased side effects 1:

  • Advanced age (especially >80 years)
  • Female sex
  • Small body frame and frailty
  • Multiple medications
  • Perioperative periods

• Drug interactions: Check for medications that may increase statin toxicity 1, 3:

  • Fibrates (especially gemfibrozil)
  • Cyclosporine
  • Azole antifungals
  • Macrolide antibiotics
  • HIV protease inhibitors

When to Seek Specialist Consultation

• If symptoms persist despite multiple statin trials
• If CK is elevated >10 times ULN
• If symptoms are severe or include objective muscle weakness
• If there is suspicion of statin-associated autoimmune myopathy (requires neurologist evaluation) 1

Remember that most patients who experience mild to moderate statin-associated symptoms can eventually tolerate at least one statin regimen with appropriate management 1, 5.