Simvastatin - forsigtig brug hos patienter over 70?
Bemærk at indholdet på denne side er mere end ét år gammel. Indholdet afspejler derfor ikke nødvendigvis IRFs nuværende holdning.
Rhabdomyolyse er en sjælden, men alvorlig bivirkning ved statiner. Med baggrund i polyfarmaci, ændret lægemiddelmetabolisme og lav muskelmasse, har ældre i statinbehandling en øget risiko for myotoksicitet. Derfor anbefales forholdsregler ved behandling af denne aldersgruppe.
Den kliniske effekt af statiner i ældre synes sammenlignelig med effekten hos midaldrende, men blandt statiner er det bedst dokumenteret for simvastatin og pravastatin. Fluvastatin og pravastin har tilsyneladende en lavere risiko for myotoxicitet end simvastatin, da disse stoffer har færre interaktioner med andre præparater. Disse forhold kan være et argument for at foretrække pravastatin blandt statiner ved behandling af ældre, der har risiko for polyfarmaci. Ved valg af behandling bør man også være opmærksom på at der er evidens for en bedre effekt på risikoen for slagtilfælde (stroke) efter langtidsbehandling med simvastatin end med pravastatin, og at prisen på pravastatin behandling pt. er mange gange dyrere end simvastatin behandling.
Should simvastatin be used with precaution in patients over the age of 70 years?
Which statin should be preferred in elderly?
A 73-year-old woman with hypertension, diabetes and hypercholesterolaemia is treated with simvastatin. In the package insert leaflet she has read that the drug not should be used in patients over the age of 70 years.
Only one package insert leaflet of a simvastatin prepration has been located, which mentions a precaution to patients over 70 years. It states that the physician should be informed about the age (1). In several summaries of product characteristics (SPC), it is stated under precautions, that a baseline creatine kinase (CK) should be measured in patients with predisposing factors for rhabdomyolysis, such as age over 70 years, renal insufficency or alchohol abuse (2,3). When rhabdomyolysis occurs in association with statin therapy, it is commonly a result of drug-drug interactions rather than a specific adverse response to statin monotherapy. (4,5). Polypharmacy and altered drug metabolism, multiple systemic diseases and low muscle mass put the elderly patient at increased risk of myotoxicity when drugs in the statin class are adminstered (5,6). Pravastatin and fluvastatin have a lower potential for drug-drug interaction than other statins, and, apparently, carries a lower risk of rhabdomyolysis (4).
The clinical efficacy and safety of statin therapy has mainly been established from large-scale trials including patients, primarily, under the age of 70 years (6,7). Until recently only subgroup analysis of these trials were available as documentation for the use in elderly, and as a consequence the use of statins in elderly patients has been a controversy (6,7). However, now there are much more conclusive evidence from the Heart Proctection Study (HPS)(8) as well as the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) (9) to confirm that statins are beneficial to the at-risk elderly in the same way as middle-aged. The HPS study was the first prospective randomized study to include a substantial number of high-risk elderly patient (n=5806>70 years), and these patient showed similar risk reductions with simvastatin treatment as their younger counterparts (8). The PROSPER study was the first dedicated randomized controlled study of statins in elderly. 5804 elderly with high risk of cardiovascular disease, aged 70-82, was assigned to receive pravastatin 40 mg daily or placebo (9). Pravastatin given for three years reduced the risk of coronary disease but the signal was weaker than for simvastatin in the HPS study (8,9). In the PROSPER study pravastatin did not reduce the risk of stroke, which was surprising in light of subgroup analyses from previous trials including the HPS study, but may be due to the relatively short follow-up in the PROSPER study (9). A recent meta-analysis (10) found that pravastatin 40 mg had less effect on stroke than other statins, while there is evidence for a better effect on stroke after long-term treatment with simvastatin. In the PROSPER study new cancer diagnoses were more frequent on pravastatin than placebo. Incorporation of this finding in a meta-analysis of pravastatin showed no overall increase in risk (9). The use of pravastatin in The PROPSPER study was not associated with any increase in hepatic or muscular side effects, despite the high concomitation medication rates in this population (8).
Another factor that have contributed to the debate on the use of statins in the elderly are life expectancy and the cost-effectiveness of statin therapy in elderly (7).
Rhabdomyolysis is a rare, but severe adverse reaction to statins. Due to possible polypharmacy and altered drug metabolism and low muscle mass, elderly in statin treatment have an increased risk of myotoxicity and that is why precaution is recommended in this age group.
Statins in elderly seem to be as efficient as in middle-aged patients, but the best evidence is available for simvastatin and pravastatin. Pravastatin and fluvastatin apparently have a lower risk of rhabdomyolysis than simvastatin, because of a less pronounced interaction profile These facts might be an argument to prefer pravastatin among the statins in elderly at risk of polypharmacy. In decision of treatment, it should also be noted, that there is evidence for a better effect on stroke after long-term treatment with simvastatin than pravastatin therapy, and that currently, pravastatin is many time more expensive than simvastatin therapy.
- Indlægsseddel. UND Simvastatin. Laegemiddelkataloget (The Danish Drug Catalogue) (Cited 05-01-11) http://www.lk-online.dk/.
- Simvastatin "UNP". Summary of Product Characteristics.The Danish Medicines Agency (Cited 05-01-11) http://www.dkma.dk.
- Zocor. Summary of Product Characteristics.The Danish Medicines Agency (Cited 05-01-11) http://www.dkma.dk.
- The Drug Information Center, Odense, Denmark. Case no 1010 (year 2002).
- Sica DA, Gehr TW. Rhabdomyolysis and statin therapy: relevance to the elderly. Am J Geriatr Cardiol. 2002 Jan-Feb;11(1):48-55.
- Holme I, Tonstad S. Treatment with statins of the elderly. Tidsskr Nor Laegeforen. 2004 Jan 22;124(2):167-9.
- Mungall MM, Gaw A. Statin therapy in the elderly. Curr Opin Lipidol. 2004 Aug;15(4):453-7.
- Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM et al. PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002 Nov 23;360(9346):1623-30.
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22.
- Cheung BMY, Lauder IJ, Lau CP, Kumana CR (2004). Meta-analysis of large randomized controlled trials to evaluate the impact of statisn on cardiovascular outcomes. Brit j Clin Pharmacol;57:640-51.
Institut for Rationel Farmakoterapi, 28. juli 2005.