Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial (2023)

Results 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups.

If you are using rosuvastatin, would you switch to atorvastatin? What do you think of this study?

Whereas lipophilic statins such as atorvastatin can cross cellular membranes through passive diffusion and are therefore widely distributed in different tissues, hydrophilic statins such as rosuvastatin are more liver selective owing to the active carrier mediated uptake mechanism, and thus they are more limited in their ability to have additional effects beyond cholesterol lowering (pleiotropic effects) in extrahepatic tissues

That rosuvastatin is hydrophilic and more hepatoselective could be useful to not decrease brain desmosterol levels for apoE4 carriers.

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Odd dosage in the study, if I read it correctly. “(12.8) mg in the atorvastatin group”

Normal:
“Generic name: atorvastatin [ a-TOR-va-sta-tin ]
Brand names: Atorvaliq, Lipitor
Dosage forms: oral suspension (20 mg/5 mL), oral tablet (10 mg; 20 mg; 40 mg; 80 mg)”

I have been taking 40 mg daily for decades with no ill effects that I am aware of.

Two arguments for atorvastatin.
I. I tried some other statins and atorvastatin was the one that produced the least amount of side effects. (I have not tried rosuvastatin.)
2. Atorvastatin is one of the most studied drugs in history, with literally many 10’s of thousands of people studied.

Atorvastatin may not be the best statin, but it is the most studied and I know what I am getting.

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The mean daily dosage was 36 mg for atorvastatin and 17.1 mg for rosuvastatin, meaning most were at 40 mg or 20 mg, respectively. It is promising that it showed fewer side effects in this study compared to rosuvastatin.

What does @Virilius think?

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At first glance it does appear that atorvastatin is the somewhat safer drug. If one is at risk of diabetes and can tolerate either statin, perhaps using atorvastatin might be the better alternative.

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