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Pharmacoepidemiol Drug Saf. 2017 Mar;26(3):285-293. doi: 10.1002/pds.4171. Epub 2017 Jan 26.

Comparative effectiveness of recommended versus less intensive drug combinations in secondary prevention of acute coronary syndrome.

Bezin J1,2,3,4, Groenwold RH5,6, Ali MS5,6, Lassalle R4,7, Robinson P4,7, de Boer A5,6, Moore N1,2,3,4, Klungel OH5,6, Pariente A1,2,3.

Author information

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.
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.
ADERA, Pessac, France.



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.


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.


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.


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.


acute coronary syndrome; comparative effectiveness research; proportional hazards models; secondary prevention

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