Results of a retrospective database analysis of adherence to statin therapy and risk of nonfatal ischemic heart disease in daily clinical practice in Italy

Background: Previous studies have reported that statin use was associated with reductions in cardiovascular morbidity and mortality among patients with dyslipidemia, even without established cardiovascular disease. However, inadequate adherence may reduce statins' protective effects. Objective: The aim of this work was to investigate whether an association exists between statin adherence when used as primary prevention and risk of subsequent ischemic heart disease (IHD). Methods: People aged ≥18 years who were residents of Italy's Lombardy region and were newly treated with statins in 2002 to 2003 were assessed as part of a retrospective analysis of data from a healthservices database. Patients who were hospitalized for IHD during this period were identified with hospitaldischarge information from a health-services database; IHD-related hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes for acute myocardial infarction (410), acute and subacute forms of IHD (411), and/or codes concerning coronary revascularization (36.0-36.9). Four groups of patients were excluded: those with ≥1 lipid-lowering drug within 2 years before the index prescription (to limit the sample to treatment initiators); those who had been hospitalized for cardiovascular disease or had used medications for IHD or heart failure within 2 years before the index date (to limit the study to primary prevention); those who did not have ≥1 year of follow-up; and those who received only 1 dispensation of a statin during the first year after the index prescription. Follow-up continued until hospitalization for IHD or any other cardiovascular cause, death from any cause, emigration, or the end of the study period (June 30, 2007). The proportion of days covered (PDC) by therapy with statins was the exposure variable; it served as a proxy for adherence. PDC (and therefore adherence) was categorized as very low (≤25%), low (26%-50%), intermediate (51%-75%), or high (≥75%) coverage. A proportional hazards model was fitted to estimate hazard ratio (HR) and 95% CIs for the association between time-dependent categories of PDC and time of IHD hospitalization, after correcting for covariates. Results: A group of 90,832 patients was included; during follow-up, 1480 patients experienced a hospitalization for IHD. After the Cox proportional hazards model was adjusted for age, sex, type of statin dispensed at index prescription, current use of other selected drugs (ie, antidiabetics, antihypertensives, digitalis or organic nitrates, or other cardiac medications), Charlson comorbidity index, and whether or not a given patient switched statins, those with low, intermediate, or high statin coverage had HR (95% CI) values of 0.85 (0.72-0.98), 0.82 (0.71-0.95), and 0.81 (0.71-0.94), respectively, compared with patients with very low coverage. Conclusions: In these Italian subjects without a history of cardiovascular disease, low, intermediate, and high levels of adherence to statin pharmaco-therapy were associated with lower risk of nonfatal IHD compared with those who had very low (≤25%) adherence. However, these findings have several limitations, such as the use of database information (rather than medical records), the assumption that PDC accurately represented actual adherence, and confounding (ie, unmeasured factors related to PDC or to adherence may have influenced clinical outcomes). © 2010.