The Risk of Muscular Events Among New Users of Hydrophilic and Lipophilic Statins: an Observational Cohort Study.
BACKGROUND: Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells.
OBJECTIVE: To compare the risk of muscular events between statins at comparable lipid-lowering doses and to evaluate if hydrophilic statins are associated with a lower muscular risk than lipophilic statins. DESIGN/SETTING: Propensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD.
PATIENTS: New statin users. Cohort 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic), cohort 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic), and cohort 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg.
MAIN MEASURES: The outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year.
KEY RESULTS: The propensity score-matched cohorts consisted of 1) 9,703, 2) 7,032, and 3) 37,743 pairs of statin users. Comparing the risk of muscular events between low-intensity pravastatin vs low-intensity simvastatin yielded a HR of 0.86 (95% CI 0.64-1.16). In the comparison of moderate- to high-intensity rosuvastatin vs equivalent doses of atorvastatin, we observed a HR of 1.17 (95% CI 0.88-1.56). Moderate- to high-intensity simvastatin was associated with a HR of 1.33 (95% CI 1.16-1.53), when compared with atorvastatin at equivalent doses.
LIMITATIONS: We could not conduct other pairwise comparisons of statins due to small sample size. In the absence of a uniform definition on the comparability of statin doses, the applied dose ratios may not fully match with all literature sources.
CONCLUSIONS: Our results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.
|ジャーナル名||Journal of general internal medicine|
|投稿者||Mueller, Alexandra M; Liakoni, Evangelia; Schneider, Cornelia; Burkard, Theresa; Jick, Susan S; Krahenbuhl, Stephan; Meier, Christoph R; Spoendlin, Julia|
|組織名||Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology,;Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.;Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.;Clinical Pharmacology and Toxicology, Department of General Internal Medicine,;Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.;Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.;Boston University School of Public Health, Boston, MA, USA.;Division of Clinical Pharmacology and Toxicology, University Hospital Basel,;Basel, Switzerland.;Department of Biomedicine, University of Basel, Basel, Switzerland.;email@example.com.|