Drug products: Crestor, Crestor®, Rosuvastatin Accord, Rosuvastatin Glenmark, Rosuvastatin Krka d.d., Rosuvastatin Medical Valley, Rosuvastatin Mylan, Rosuvastatin Orion, Rosuvastatin Sandoz, Rosuvastatin STADA, Rosuvastatin Teva, Rosuvastatin Xiromed, Visacor
ATC code: C10AA07
Substances: rosuvastatin, rosuvastatin calcium
Studies have shown similar effect of rosuvastatin in men and women.
A large register-based study has shown men and women to have similar risk of moderate to serious muscular adverse effects.
Several studies have found no sex differences in rosuvastatin pharmacokinetics [8-10]. However, a small Chinese study (6 men, 6 women), found a 5% lower AUC and 6.5% lower mean Cmax in men compared to women . Since no sex differences have been found for rosuvastatin pharmacokinetics [2-4], no dose adjustments based on patient’s sex are needed.
In general, randomized controlled trials of statins have only conducted subgroup analyses to detect potential sex differences in efficacy.
Meta-analyses conclude that statin treatment is similarly effective for secondary prevention of cardiovascular events in both men and women, although there was no benefit in mortality among women [1-3]. However, meta-analyses on the effects of statin treatment as primary prevention in women report conflicting conclusions [1, 2, 4]. Underrepresentation of women in clinical trials and lower incidence rates in women may have contributed to these conflicting results.
A meta-analysis including both primary and secondary prevention trials (in total 54 160 men, 17 818 women) concluded that statins (atorvastatin, pravastatin, simvastatin, lovastatin) reduced the risk of cardiovascular events in both men and women. Men, but not women, had a significant decrease in mortality, myocardial infarction, and stroke. It was suggested that women may have derived their benefits from a decrease in the prevalence of unstable angina in need for revascularization . However, this study did not perform separated analyses for primary and secondary prevention.
Two other meta-analyses (141 235 patients and 174 149 patients respectively, on average 73% men in both) found similar beneficial effects of statin treatment (atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin) in both primary and secondary prevention in men and women [1, 2]. Another smaller meta-analysis (in total 30 194 men, 19 052 women) conclude that primary prevention with statins (atorvastatin, lovastatin, pravastatin, simvastatin) reduce the risk of coronary heart disease events only in men. The risk of total mortality was not reduced in men or women . A meta-analysis including only secondary prevention trials (in total 34 294 men, 8897 women) concluded that statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) were similarly effective as prevention of cardiovascular events in both men and women, however there was no benefit on stroke or all-cause mortality in women .
Results from the VOYAGER meta-analysis (17 897 men, 13 662 women) showed that statins (atorvastatin, simvastatin, rosuvastatin) reduced concentrations of LDL and non-HDL and increased concentrations of HDL dose-dependently in both men and women of all ages, with largest reductions in women aged ≥70 years .
Specific for rosuvastatin
Primary prevention: In the JUPITER trial (11001 men, 6801 women), rosuvastatin treatment (20 mg/day) of healthy individuals with elevated high sensitivity CRP and normal LDL cholesterol resulted in similar risk reductions in cardiovascular disease events in both men and women. However, women had greater reduction in revascularization/unstable angina and men had greater reduction in stroke. Subgroup analysis suggested that women with a family history of premature coronary disease may benefit more from rosuvastatin therapy than those without [12, 13].The efficacy of rosuvastatin 40 mg on changes in carotid intima-media thickness (CIMT) wereas measured in the randomized, placebo-controlled METEOR trial. Results show that rosuvastatin slowed progression of maximum CIMT over 2 years and results were consistent in men and women .
Secondary prevention: The CORONA trial included patients with systolic heart failure (EF<40%), due to ischemic heart disease (3831 men, 1180 women). In this trial, rosuvastatin did not reduce death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, in patients with systolic heart failure. Rosuvastatin did reduce the number of cardiovascular hospitalizations. The treatment effect was similar in men and women .
In the JUPITER trial, rates of muscle disorders or myopathy were similar in men and women regardless of treatment assignment [12, 13].
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 moderate to serious myopathy. Adjusted hazard ratio for rosuvastatin-induced myopathy was 4.2 in men vs. 5.4 in women .
Most large pivotal studies, even recent ones, have not performed relevant sex-analyses of side effects .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
A significant association between statin therapy and decreased risk of overall fractures has been found for men but not for women .
A meta-analysis of controlled clinical trials (413 men, 480 women) report that among hyperlipidemic patients who receive long-term rosuvastatin treatment (10 mg/day for ≥96 weeks), GFR was unchanged regardless of patient’s sex. This suggests that rosuvastatin may arrest the progression of renal disease . A meta-analysis of adherence to statin treatment report that women (OR 1.10) and non-white patients (OR 1.53) were more likely to be non-adherent to their statin treatment. Non-adherence measured by self-report data demonstrated higher rates for women (OR 1.20) compared with data based on pharmacy-claims (OR 1.10) .
Date of litterature search: 2019-08-20
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson