Statins

• Dr. O’Keefe is not a fan of Atorva 80 mg b/c side effects of statins are dose-dependent.

  • You can get rhabdo with high doses of statins. Dr. O’Keefe gave an example of post-transplant patient on Atorva 80 who got rhabdo and died a few months later.
  • Delta between 40 mg and 80 mg of atorva is 48% → 51% reduction (delta is only 3%)

• Atorva is the 🌟

  • less nephrotoxicity compared to rosuvastatin

• Rule of thumb: 6% reduction when doubling a statin dose. Better off adding ezetimibe: zetia on its own 16% reduction, zetia + statin (synergistic effect): 25% reduction.

• Newborn baby LDL is 25-30 mg/dL. Hunter/gatherers have also been studied and have like 40-50 mg/dL.

  • You don’t want a 0 LDL! Cholesterol is an important molecule, so you need some.

• Dr. O’Keefe gets nervous getting someones LDL < 30

• Side effects are not related to LDL level, rather related to statin dose.

• ⚠️ Statins are contraindicated in pregnancy 🤰and lactation

• Mnemonic for statin side effects “LIPITOR”:

  • Liver effects
  • Increased blood sugar
  • Pain (muscles)
  • Impaired memory
  • Tiredness/Fatigue
  • Other (headaches)
  • Rhabdomyolysis

• SAMSON trial (BMJ, 2021)

  • 200 statin intolerant patients; “n-of-1” experiments
  • Compared atorva 20 mg vs placebo
  • Intolerable muscle sx: 9% in statin group discontinued, 7% discontinued placebo

• FDA did put out a warning on “brain fog” with statins, but meta-analysis showing ↓ Alzheimer’s Risk 32%

• Dr. O’Keefe: “when I start someone on a statin, I also start them on CoQ10.”

  • If patient c/o myalgias, he’ll increase the dose of CoQ10

• Pitavastatin

  • a “cool” statin
  • Not as strong as atorva
  • 4 mg dose $\approx$ 20 mg of atorva
  • Unlike atorva, rosuva, simva, Pitavastatin less likely to induce DM in patients. If anything pitava can lower A1c by 0.1%

High-Intensity Statins

• Rosuvastatin 20-40 & Atorvastatin 40-80 mg
• Maximally tolerated statin still the foundation
• ↓ LDL-C ~50%
• Can get creative to identify “maximally tolerated” to manage intolerance
  • Symmetric myalgias in large proximal muscle groups may indicate true statin intolerance; RARE
    • SAMSON trial - 90% of muscle symptoms attributed to “nocebo effect”
  • Rule out/correct other causes of muscle symptoms: hypothyroidism, vitamin D deficiency, exercise
  • Hydrophilic statins potentially less muscle symptoms (rosuvastatin, pravastatin)
  • Up to 90% of initially intolerant do fine with re-challenge
    • Allow 2-4 week wash out

Variability in individual response to statins