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Atorvastatin

Klassificering: A

Preparat: 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 Ranbaxy, Atorvastatin Sandoz, Atorvastatin Teva, Atorvastatin Xiromed, Lipistad, Lipitor, Lipitor®, Sortis, Tahor, Tavara, Torvast, Zarator

ATC kod: C10AA05

Substanser: atorvastatin, atorvastatinkalcium, atorvastatinkalcium, amorf, atorvastatinkalciumisopropanolat, atorvastatinkalciumpropylenglykolsolvat, atorvastatinkalciumtrihydrat

Sammanfattning

Studier har visat att atorvastatin vid sekundärprevention reducerar risken för kardiovaskulära händelser på ett likvärdigt sätt hos kvinnor och män.
En stor studie har visat att män har större risk att drabbas av måttliga till svåra muskelbiverkningar av atorvastatin. Mindre studier har dock inte visat någon könsskillnad i förekomst av muskelbiverkningar.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Pharmacokinetics and dosing

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].

Effects

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 [4].

Secondary prevention

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 [5].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 [6].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 [7].

Adverse effects

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 [8]. 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 [9]. A post-hoc analysis of the SPARCL study showed no sex differences in adverse events [5].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

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 [1].

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande atorvastatin (ATC-kod C10AA05) på recept i Sverige år 2015, totalt 188 480 män och 136 968 kvinnor. Det motsvarar 39 respektive 28 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-84 år hos båda könen. I genomsnitt var tabletter innehållande atorvastatin 1,7 gånger vanligare hos män [10].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2014-05-07

Referenser

  1. Foody JM, Joyce AT, Rudolph AE, Liu LZ, Benner JS. Persistence of atorvastatin and simvastatin among patients with and without prior cardiovascular diseases: a US managed care study. Curr Med Res Opin. 2008;24:1987-2000. PubMed
  2. Gibson DM, Bron NJ, Richens A, Hounslow NJ, Sedman AJ, Whitfield LR. Effect of age and gender on pharmacokinetics of atorvastatin in humans. J Clin Pharmacol. 1996;36:242-6. PubMed
  3. García MJ, Reinoso RF, Sánchez Navarro A, Prous JR. Clinical pharmacokinetics of statins. Methods Find Exp Clin Pharmacol. 2003;25:457-81. PubMed
  4. Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149-58. PubMed
  5. Goldstein LB, Amarenco P, Lamonte M, Gilbert S, Messig M, Callahan A et al. Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study. Stroke. 2008;39:2444-8. PubMed
  6. Athyros VG, Kakafika AI, Papageorgiou AA, Paraskevas KI, Tziomalos K, Anagnostis P et al. Effects of statin treatment in men and women with stable coronary heart disease: a subgroup analysis of the GREACE Study. Curr Med Res Opin. 2008;24:1593-9. PubMed
  7. Truong QA, Murphy SA, McCabe CH, Armani A, Cannon CP, TIMI Study Group. Benefit of intensive statin therapy in women: results from PROVE IT-TIMI 22. Circ Cardiovasc Qual Outcomes. 2011;4:328-36. PubMed
  8. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J et al. Effect of statins on skeletal muscle function. Circulation. 2013;127:96-103. PubMed
  9. Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340:c2197. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler, Expertrådet för hjärt-kärlsjukdomar

Godkänt av: Karin Schenck-Gustafsson