Hydrophilic statins as toxic to muscle as lipophils

The iatrogenic muscle risk (myalgia, myositis, rhabdomyolysis) associated with statins has been known for a long time. In various clinical trials, 1.5% to 5% of patients experienced this type of side effect during treatment with statins. In real life, they are up to 10-15%. This myotoxicity appears to be dose-dependent and vary depending on the molecules. Hydrophilic statins (rosuvastatin and pravastatin) may be less myotoxic than lipophils (such as simvastatin or atorvastatin) due to less passive diffusion into muscle cells.

This hypothesis was refuted by an observational study carried out using a British national registry (United Kingdom-based Clinical Practice Research Datalink GOLD), which contains anonymized data from more than 15 million patients. Published in March 2021, its results show that the relative risk of iatrogenic muscle effect in the year following the start of treatment with different statins, at equivalent dosage, is not systematically lower with hydrophilic molecules since it reaches :

  • 0.86 for patients on pravastatin (hydrophilic) compared to those on simvastatin (lipophilic),
  • 1.17 under rosuvastatin (hydrophilic) versus atorvastatin 10-80 mg (lipophilic),
  • 1.33 on simvastatin (lipophilic) vs atorvastatin (lipophilic).

The muscular effects declared are myalgia in 98% of cases.

The risk of muscular events among new users of hydrophilic and lipophilic statins: an observational cohort study. Mueller AM, Liakoni E, Schneider C et al. J Gen Intern Med. 2021 Mar 9.