Rosuvastatin (Crestor)

Rosuvastatin is the most potent approved statin. It inhibits the same HMG-CoA reductase as atorvastatin but binds more strongly and for longer. In practice that means: at the same milligram figure it lowers LDL more.

The second difference is pharmacokinetic and at least as important day to day: rosuvastatin is barely metabolised through CYP3A4 and is mostly excreted unchanged. Anyone taking other substances that run through that enzyme has considerably fewer conflicts here.

This information is for research and educational purposes only. No medical advice.

Rosuvastatin is hydrophilic, meaning water-soluble, and enters the liver cell through a dedicated transporter rather than simply diffusing through any cell membrane. That is part of why the muscle burden is comparatively favourable relative to its potency.

With a half-life of around 19 hours the time of day does not matter, unlike with the short-acting statins. A fixed time still helps, simply so the dose does not get forgotten.

A point that often gets lost: in people of East Asian ancestry plasma levels average roughly twice those in Europeans, which is why lower starting doses are used there. That is not a footnote, it is stated in the prescribing information.

JUPITER (NEJM 2008) is the best known and most debated trial. Almost 18,000 people without elevated LDL but with elevated CRP as an inflammation marker received 20mg rosuvastatin or placebo. The trial was stopped after barely two years: the primary combined endpoint fell by 44 percent. The main criticism was that the absolute event rate was low, which makes the relative figure look more impressive than the absolute benefit.

HOPE-3 (NEJM 2016) tested the same idea at intermediate risk without prior disease and found 24 percent fewer events. ASTEROID (JAMA 2006) showed on intravascular ultrasound that existing plaque actually regresses under 40mg, rather than merely growing more slowly.

SATURN (NEJM 2011) compared rosuvastatin 40mg directly with atorvastatin 80mg. Both regressed plaque, and on the primary ultrasound measure there was no significant difference between them. Rosuvastatin achieved a lower LDL in the process, which raises the question of how tightly the LDL number and plaque regression are really coupled.

• Muscle pain: possible as with all statins. Anyone training hard has elevated CK anyway. New, unfamiliar muscle pain on a statin needs checking.
• Protein in urine: described at 40mg, usually transient and without disease significance, but the reason for caution with the maximum dose.
• Liver values: small rises common, clear rises need checking.
• Blood sugar: slightly raised risk of new-onset diabetes, as with the whole class.

Store dry, at room temperature and protected from light. Keep out of reach of children.