title: Self-controlled case-series study to verify the effect of adherence to Beta-blockers in secondary prevention of myocardial infarction.
abstract: BACKGROUND
  Beta-blockers (BB) are recommended in secondary prevention of acute myocardial infarction (AMI), but adherence to prescription medication is a recognized problem. Most literature on the consequences of poor adherence to prescribed BB is limited by the possibility of "healthy adherer bias" and better-designed studies have been advocated.
  
  
  RESULTS
  We investigated the association between adherence to BB prescription and risk of subsequent AMIs using the self-controlled case series design, which allows improved control of interpersonal confounding, being based on intrapersonal comparisons. From all the 30 089 patients hospitalized for AMI in the years 2009-2011 in an Italian region we selected those that suffered subsequent AMIs at days 31 to 365 from discharge (1328), and then the 1207 that had at least one BB prescription collected at any of the regional pharmacies. Using information on prescriptions, each individual's observation time was then divided into periods exposed or unexposed to BB and the relative AMI incidence rate ratios (IRR) of BB exposure were estimated by conditional Poisson regression. The IRR (rate of recurrent AMI in exposed versus unexposed periods) was 0.79 (95% CI 0.69 to 0.90, P=0.001). Various sensitivity analyses confirmed the robustness to possible failure of assumptions, ie, considering only first recurrences (IRR 0.76, 95% CI 0.66 to 0.88, P<0.001), excluding cardiovascular fatalities (IRR 0.76, 95% CI 0.65 to 0.89, P<0.001), and excluding individuals with long hospital admissions (IRR 0.60, 95% CI 0.43 to 0.83, P=0.002).
  
  
  CONCLUSIONS
  Adherence to recommended BB therapy was associated with a 20% reduction of recurrent AMIs, consistently with previous research, but with decreased concerns about healthy-adherer bias.
authors.affiliation: Regional Agency for Health and Social Care of Emilia-Romagna/Azienda Ospedaliero-Universitaria di Udine, Bologna/Udine, Italy (S.D.B., M.M., P.G., R.D.P.).
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Bartolomeo
authors.affiliation: Regional Agency for Health and Social Care of Emilia-Romagna/Azienda Ospedaliero-Universitaria di Udine, Bologna/Udine, Italy (S.D.B., M.M., P.G., R.D.P.).
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Marino
authors.affiliation: Regional Agency for Health and Social Care of Emilia-Romagna/Azienda Ospedaliero-Universitaria di Udine, Bologna/Udine, Italy (S.D.B., M.M., P.G., R.D.P.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Guastaroba
authors.affiliation: Servizio di Epidemiologia, Direzione Centrale Salute, Integrazione Sociosanitaria e Politiche Sociali, Regione Autonoma Friuli Venezia Giulia, Udine, Italy (F.V.).
authors.forename: Francesca
authors.initials: F
authors.lastname: Valent
authors.affiliation: Regional Agency for Health and Social Care of Emilia-Romagna/Azienda Ospedaliero-Universitaria di Udine, Bologna/Udine, Italy (S.D.B., M.M., P.G., R.D.P.).
authors.forename: Rossana
authors.initials: R
authors.lastname: De Palma
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D016022:Case-Control Studies; D003266:Continuity of Patient Care; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control*; D010349:Patient Compliance / Q000706:statistics & numerical data; D010351:Patient Discharge / Q000706:statistics & numerical data; D012008:Recurrence; D012042:Registries; D012189:Retrospective Studies; D055502:Secondary Prevention / Q000379:methods*; D016903:Drug Monitoring
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: adrenergic β‐antagonists; bias (epidemiology); medication adherence; myocardial infarction; secondary prevention