Drug products: Pravachol, Pravachol®, Pravastatin Nycomed, Pravastatin Omnia, Pravastatin Ranbaxy, Pravastatin Rivopharm, Pravastatin Sandoz, Pravastatin Teva
ATC code: C10AA03
Substances: pravastatin, pravastatin sodium
Studies have shown that pravastatin as primary and secondary prevention reduces mortality and morbidity equally in men and women.
A large registry-based study has shown men and women to have similar risk of moderate to severe muscular adverse effects.
Only small differences in the pharmacokinetic profile of pravastatin in young and elderly men and women have been demonstrated [8, 9]. Based on the findings in pravastatin pharmacokinetics [8, 9], dosage modification in elderly men or women are not recommended by the pharmaceutical company.
Pravastatin is a substrate of the hepatic uptake transporter OATP1B1. The effect of gene polymorphism on the pharmacokinetics of pravastatin was studied in a Finnish study (18 men, 14 women). Cmax and AUC of pravastatin were markedly higher in women with the c.521TT genotype than in men with the same genotype .
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 pravastatin
Trials of pravastatin as primary and secondary prevention show similar results in men and women.
Primary prevention: The large ALLHAT-LLT trial (5304 men, 5051 women) compared pravastatin 40 mg/day with “usual care” in hypercholesterolemic, hypertensive patients with at least one additional CHD risk factor. All-cause mortality did not differ between the pravastatin and usual care treatment groups, and the results were similar in men and women .Results from the Japanese MEGA study (2476 men, 5356 women; mean age 59.7 years in women, 55.2 years in men) show that treatment with pravastatin 10-20 mg/day in patients with elevated cholesterol but without previous cardiovascular disease similarly decreased incidence of cardiovascular events and total mortality in men and women. The incidence of cardiovascular events was lower in women than in men, probably due to lower percentage of smokers among women .
Secondary prevention: The LIPID trial (7498 men, 1516 women) was a double-blind, randomized trial, comparing pravastatin 40 mg/day with placebo in patients with coronary heart disease and a broad range of cholesterol levels. The mortality risk reduction with pravastatin was similar in men and women .In the double-blind placebo-controlled CARE trial (3577 men, 582 women), patients with myocardial infarction and average cholesterol levels were treated with pravastatin 40 mg/day for 5 years. The beneficial effect of pravastatin on major coronary events was greater among women than in men .The effect of pravastatin on hsCRP levels was evaluated in the PRINCE trial (1764 men, 1120 women), including a primary prevention cohort and a secondary prevention cohort. Pravastatin 40 mg/day reduced hsCRP levels at 24 weeks in both cohorts. Compared to placebo, the effect of pravastatin on hsCRP levels was significant in both men and women. The median change in hsCRP was similar in men and women .
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 HR for pravastatin-induced myopathy was 4.8 in men vs. 2.6 in women .
Most large pivotal studies, even recent ones, have not performed relevant sex-analyses of adverse effects . However, this was done in the LIPID study  where no sex differences in adverse effects were reported.
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 three large-scale clinical trials (in total 7082 men, 6642 women) studied the influence of pravastatin therapy on cancer morbidity and mortality in Japanese patients. No increased risk for cancer incidence and cancer death following administration of pravastatin was detected in either men or women . 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