ORIGINAL REPORT Statin usage and all-cause and disease-specific mortality in a nationwide study Jari Haukka 1,3 *, Leo Niskanen 2 , Timo Partonen 3 , Jouko Lönnqvist 3 and Jari Tiihonen 4 1 Department of Public Health, University of Helsinki, Helsinki, Finland 2 Department of Medicine, University of Kuopio, Helsinki, Finland 3 Department of Mental Health and Alcohol Research, National Institute for Health and Welfare, Helsinki, Finland 4 Department of Forensic Psychiatry, University of Kuopio, Helsinki, Finland ABSTRACT Context The consumption of statins (HMG-CoA reductase inhibitors) in most Western countries has increased to the extent that it may affect all-cause and disease-specific mortality. Objective To analyze the association of statin use with all-cause and disease-specific mortality utilizing nationwide databases in a record linkage study in Finland. Methods The study population included all statin users in Finland who had purchased at least one prescription between 1997 and 2005. A control population matched for age, sex, and place of residence and without statin usage was selected. The study population consisted of 336 618 pairs of individuals, and the mean length of follow-up was 4.4 years. All-cause mortality and mortality caused by coronary heart disease (CHD), stroke, other circulatory causes, cancer, unnatural causes, and suicide were analyzed. Persistence to treatment was calculated by varying adherence criteria between 20 and 80%. Results We observed association between all-cause, non-CHD and CHD and treatment with statins in statin user group. For CHD mortal- ity, we observed a relationship between the persistence to statin treatment and a decreasing CHD mortality. For each 10% increase in adher- ence criteria, a 5% (2–8%) decrease in CHD mortality was observed within the range of 20% (RR 0.81, 95%CI 0.32–2.02) to 80% (RR 0.54, 95%CI 0.46–0.64). Conclusion In this nationwide study, long-term use of statins is associated with the reduction in CHD mortality. Copyright © 2011 John Wiley & Sons, Ltd. key words—statins; mortality; pharmacoepidemiology Received 25 August 2010; Revised 18 August 2011; Accepted 19 August 2011 INTRODUCTION Meta-analyses from an impressive number of random- ized clinical trials (RCTs) indicate that statins (HMG- CoA reductase inhibitors) potently reduce both total and low-density lipoprotein cholesterol levels and de- crease the incidence of both cardiovascular and cere- brovascular events by 25–40%, similarly in both non-diabetic and diabetic patients. 1,2 In Finland, sta- tins are one of the most utilized therapeutic class of prescription drugs (83 defined daily dose per 1000 in 2008) with about 500 000 users (10% of the population) at present. 3 A meta-analysis in 90 000 patients demonstrated in RCTs that statins decrease to- tal and cardiovascular mortalities by about 5–9% per year. 1,4–6 However, interpreting theses results for effec- tiveness or efficacy in the real-world setting remains a challenge. 7–10 In the clinical setting, patients with more comorbidities than those in RCTs are probably treated with statins. Furthermore, it has been observed that under-treatment of high-risk subjects remains relatively common 11 and largely unrecognized. It has been suggested that statin usage also may have an impact on other causes of death besides cardiovascular mortality. Meta-analyses have been carried out to study the association between statin utilization and the risk of cancer. 12–14 According to these meta-analyses, statins had a neutral effect on cancer: no type of cancer was *Correspondence to: Jari Haukka, Department of Public Health, University of Helsinki, PO Box 41, FIN-00014 University of Helsinki, Finland. E-mail: jari. haukka@helsinki.fi Copyright © 2011 John Wiley & Sons, Ltd. pharmacoepidemiology and drug safety 2012; 21: 61–69 Published online 29 September 2011 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pds.2255