Statin Use and Risk of Atrial Fibrillation or Flutter: A Population-based Case–Control Study Giacomo Veronese, BSc, Jonathan Montomoli, MD,* Morten Schmidt, MD, Erzs ebet Horváth-Puhó, MSc, PhD, and Henrik Toft Sørensen, MD, PhD, DMSc The pleiotropic effects of statins have been suggested to prevent atrial fibrillation onset. We con- ducted a population-based case–control study using medical databases from Northern Denmark (population: 1.8 million) to examine the association between statin use and atrial fibrillation or flutter. We identified 51,374 patients with atrial fibrillation or flutter between 1999 and 2010 and 513,670 matched population controls. We collected data on statin prescriptions redeemed within 90 days (current users) or longer (former users) before the diagnosis date of atrial fibrillation or flutter. We stratified statin users by duration of exposure, determined by the number of days between first and last redeemed prescription before the diagnosis date (,365, 365–1094, and $1095 days). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs), controlling for potential confounders. We defined people without previous statin use as never users (reference). A total of 7360 (14.3%) cases and 55,699 (10.8%) controls were current statin users. Among current users (adjusted OR: 0.96, 95% CI, 0.93–0.99), the preventive effect of statins on atrial fibrillation or flutter was related to duration of use: adjusted ORs decreased from 1.35 (95% CI, 1.28– 1.42) for users who were prescribed statins for ,365 days to 0.85 (95% CI, 0.81–0.89) for users who were prescribed statins for $1095 days compared with never users. For former users (adjusted OR: 0.94, 95% CI. 0.90–0.98), the ORs did not change with varying lengths of exposure. In conclusion, long-term statin use may reduce the risk of atrial fibrillation or flutter compared with never use. Keywords: statin, atrial fibrillation, prevention, epidemiology INTRODUCTION Hydroxymethylglutaryl-coenzyme A reductase inhib- itors, commonly known as statins, represent the cor- nerstone of blood cholesterol-lowering therapy, and thus they are unequivocally associated with a sub- stantial reduction in cardiovascular morbidity and mortality. 1,2 Atrial fibrillation is the most common arrhythmia encountered in clinical practice, 3 with a general popula- tion prevalence increasing from 0.5% at age 50–59 years to above 10% at age 80–89 years. 4 Atrial fibrillation is associated with increased mortality and morbidity, 5–7 mainly due to hemodynamic impairments and thrombo- embolic events. 8 Projections based on population-based studies in the United States indicate that the number of patients with atrial fibrillation may triple by 2050. 9 Thus, there is a significant need for primary prevention. Department of Clinical Epidemiology, Aarhus University Hospi- tal, Aarhus, Denmark. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus Uni- versity. None of these studies has any relation to the present study. The study was supported by the Clinical Epidemiology Research Foundation, Denmark. These funding sources had no role in the design, conduct, analysis, or reporting of this study. The authors have no conflicts of interest to declare. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions this article on the journal’s Web site (www.americantherapeutics.com). *Address for correspondence: Department of Clinical Epidemiol- ogy, Aarhus University Hospital, Olof Palmes All  e 43-45, Aarhus N DK-8200, Denmark. E-mail: jm@dce.au.dk American Journal of Therapeutics 0, 000–000 (2013) 1075–2765 Ó 2013 Lippincott Williams & Wilkins www.americantherapeutics.com Copyright ª Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.