Statins

	High Intensity	Moderate Intensity	Low Intensity
LDL-C Lowering	≥50%	30%–49%	<30%
Statins	Atorvastatin (40 mg) 80 mg Rosuvastatin 20 mg (40 mg)	Atorvastatin 10 mg (20 mg) Rosuvastatin (5 mg) 10 mg Simvastatin 20–40 mg	Simvastatin 10 mg
		Pravastatin 40 mg (80 mg) Lovastatin 40 mg (80 mg) Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 1–4 mg	Pravastatin 10–20 mg Lovastatin 20 mg Fluvastatin 20–40 mg
Table source: Table 3 of 1

• 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

• 📝 At equivalent statin doses, Asians achieve greater LDL lowering than Westerners

  • ∴ Consider starting with lower dose (1/4 dose) in Asians

• 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

Drug-Drug Interactions

Simvastatin

• Risk of myopathy, including rhabdomyolysis, is ↑ by concomitant administration of:
  • CCBs Verapamil or Diltiazem
    • 📝 Simvastatin dose should not exceed 10 mg/day!
  • Amiodarone, Amlodipine or Ranolazine
    • 📝 Simvastatin dose should not exceed 20 mg/day!

Footnotes

1. Grundy, S, Stone, N, Bailey, A. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. JACC. 2019 Jun, 73 (24) 3168–3209. https://doi.org/10.1016/j.jacc.2018.11.002 ↩