title: Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome.
abstract: OBJECTIVE
  The secondary prevention treatment for acute coronary syndrome (ACS) is based on the combined use of drugs from four therapeutic classes (beta-blockers, antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). The objective of this study was to compare the long-term effectiveness of the recommended therapeutic combination with those of incomplete combinations in secondary prevention of ACS.
  
  
  METHODS
  This cohort study used data from a representative sample of the French national healthcare insurance system database. Patients hospitalised for an incident ACS between 2006 and 2011 and aged ≥20 years at the time of ACS were included in the study. Effectiveness in preventing the composite outcome ACS, transient ischemic attack, ischemic stroke or all-cause-death was estimated using time-fixed and time-dependent Cox proportional hazards models with different definitions of exposure (at inclusion or determined daily during follow-up) and adjustment for patient characteristics, co-morbidities and co-medications.
  
  
  RESULTS
  Of the 2874 patients included in the study, 33.9% were women; median age was 67 years (interquartile range: 56-77). The median duration of follow-up was 3.6 years (interquartile range: 2.2-5.3). Compared with the use of recommended combination, use of combination with three classes increased the risk of the composite outcome from 1.25 (95% confidence interval (95%CI), [1.07-1.47]) in the time-fixed model and from 1.40 (95%CI, [1.15-1.70]) or 1.42 (95%CI, [1.13-1.79]) in the time-dependent models.
  
  
  CONCLUSIONS
  After ACS, the use of incomplete drugs combinations compared with the recommended four drugs combination was associated with a higher risk of cardiovascular morbidity and all-cause mortality. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: University of Bordeaux, U1219, Bordeaux, France.|Department of Clinical Pharmacology, University Hospital of Bordeaux, Bordeaux, France.|INSERM, U1219, Bordeaux Population Health Research Center, Pharmacoepidemiology Research Team, Bordeaux, France.|Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France.
authors.forename: Julien
authors.identifier: http://orcid.org/0000-0002-2568-1928
authors.initials: J
authors.lastname: Bezin
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M Sanni
authors.initials: MS
authors.lastname: Ali
authors.affiliation: Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France.|ADERA, Pessac, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lassalle
authors.affiliation: Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France.|ADERA, Pessac, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Robinson
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: University of Bordeaux, U1219, Bordeaux, France.|Department of Clinical Pharmacology, University Hospital of Bordeaux, Bordeaux, France.|INSERM, U1219, Bordeaux Population Health Research Center, Pharmacoepidemiology Research Team, Bordeaux, France.|Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France.
authors.forename: Nicholas
authors.identifier: http://orcid.org/0000-0003-1212-2817
authors.initials: N
authors.lastname: Moore
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.affiliation: University of Bordeaux, U1219, Bordeaux, France.|Department of Clinical Pharmacology, University Hospital of Bordeaux, Bordeaux, France.|INSERM, U1219, Bordeaux Population Health Research Center, Pharmacoepidemiology Research Team, Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Pariente
mesh_terms: D054058:Acute Coronary Syndrome / Q000517:prevention & control*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D016016:Proportional Hazards Models; D055502:Secondary Prevention / Q000379:methods*; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors
keywords: acute coronary syndrome; comparative effectiveness research; proportional hazards models; secondary prevention