Drug products: Atorab, Atorbir, Atorstad, Atorvastad, Atorvastatin 1A Farma, Atorvastatin Accord, Atorvastatin Actavis, Atorvastatin Bluefish, Atorvastatin Ebb, Atorvastatin Krka, Atorvastatin Mylan, Atorvastatin Orifarm, Atorvastatin Orion, Atorvastatin Paranova, Atorvastatin Pfizer, Atorvastatin Sandoz, Atorvastatin SUN, Atorvastatin Teva, Atorvastatin Xiromed, Lipistad, Lipitor, Lipitor®, Sortis, Tahor, Tavara, Torvast, Zarator
ATC code: C10AA05
Substances: atorvastatin, atorvastatin calcium, atorvastatin calcium amorphous, atorvastatin calcium isopropanolate, atorvastatin calcium propylene glycol solvate, atorvastatin calcium trihydrate
Studies have shown that during secondary prevention, atorvastin reduces the risk of cardiovascular events equally among men and women.
A large study has shown that men have a greater risk of moderate to severe muscular adverse effects of atorvastatin. However, smaller studies have not shown any sex difference regarding the presence of muscular adverse effects.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
The effect of sex on the pharmacokinetics of atorvastatin was evaluated after administration of single 20 mg tablets to young and elderly men and women (16 men, 16 women). Maximum plasma concentration (Cmax) was 18% higher in women than in men, while AUC was 11% lower in women. The confidence intervals were wide and no significance analysis was performed. The authors considered the pharmacokinetic sex differences too small to warrant dosage modification [2, 3].
ASCOT-LLA was a double-blind randomized study of atorvastatin in hypertensive patients with at least three other risk factors for cardiovascular disease. In a subgroup analysis (10305 men, 1942 women), a beneficial effect of atorvastatin 10 mg/day was shown in men, but could not be confirmed in women, possibly due to the low number of events in women .
A post hoc analysis of the SPARCL trial (2823 men, 1908 women) found that stroke and other cardiovascular events were similarly reduced with atorvastatin 80 mg/day in men and women with a recent stroke or TIA .A post hoc analysis was also performed in the GREACE study (1256 men, 344 women), which investigated the extent in vascular event reduction by atorvastatin treatment according to sex. Treatment with atorvastatin 80 mg/day for 3 years reduced cardiovascular heart disease, morbidity and mortality by about 50% in both men and women compared with “usual care” (e.g. low fat diet, weight loss, exercise, lipid-lowering drugs). Men and women may have gained additional benefit through different mechanisms; men had a substantially larger increase in HDL cholesterol and women a significantly greater reduction in triglycerides .A subgroup analysis of the PROVE IT-TIMI 22 trial (509 men, 170 women), showed that atorvastatin 80 mg/day after acute coronary syndrome led to a reduction in cardiovascular events in both women and men .
In a large register-based cohort study (121 148 men, 104 744 women), the risk of moderate to serious myopathy was higher in men than in women for lipophilic statins such as simvastatin and atorvastatin. However, for the hydrophilic statins such as rosuvastatin and pravastatin there were no sex differences in the risk of myopathy. Adjusted HR for atorvastatin-induced myopathy was 6.7 in men vs. 2.9 in women . However, in the prospective placebo-controlled STOMP study (The effects of Statins on Skeletal Muscle Function and Performance) (214 healthy men, 216 healthy women, of different ages), no difference in myalgia was reported between men and women . A post-hoc analysis of the SPARCL study showed no sex differences in adverse events .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Studies of adherence to statin therapy show conflicting results depending on study population. In a study from the U.S. (93006 men, 90594 women), female patients were more likely to be non-adherent to their prescribed statin .
Date of litterature search: 2014-05-07
Reviewed by: Mia von Euler, Expertrådet för hjärt-kärlsjukdomar
Approved by: Karin Schenck-Gustafsson