title: Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors.
abstract: BACKGROUND
  Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. OBJECTIVE :To identify a proxy for ACEI-induced ADRs in prescription databases.
  
  
  METHODS
  The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older.
  
  
  METHODS
  All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated.
  
  
  RESULTS
  Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %.
  
  
  CONCLUSIONS
  Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, David de Wied Building, 3508 TB, Utrecht, The Netherlands.
authors.forename: Seyed Hamidreza
authors.initials: SH
authors.lastname: Mahmoudpour
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.|Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.|Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: de Keyser
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, David de Wied Building, 3508 TB, Utrecht, The Netherlands.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Souverein
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, David de Wied Building, 3508 TB, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, David de Wied Building, 3508 TB, Utrecht, The Netherlands. a.h.maitland@uu.nl.
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D060735:Pharmacovigilance; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D055656:Prescriptions / Q000706:statistics & numerical data*; D011320:Primary Health Care / Q000706:statistics & numerical data; D011446:Prospective Studies; D015203:Reproducibility of Results
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents
keywords: ACEI; ADR; Adverse drug reaction; Angiotensin converting enzyme inhibitors; Electronic healthcare database; PPV; Pharmacoepidemiology; Pharmacovigilance; Positive predictive value