• Alexandra M Mueller, Evangelia Liakoni, Cornelia Schneider, Theresa Burkard, Susan S Jick, Stephan Krähenbühl, Christoph R Meier, and Julia Spoendlin.
• Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
• J Gen Intern Med. 2021 Sep 1; 36 (9): 2639-2647.

BackgroundStatins 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.ObjectiveTo 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/SettingPropensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD.PatientsNew 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 MeasuresThe outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year.Key ResultsThe 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.LimitationsWe 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.ConclusionsOur results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.© 2021. The Author(s).

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