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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.

Original publication




Journal article


Pharmacoepidemiology and drug safety

Publication Date





285 - 293


Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France.


Humans, Adrenergic beta-Antagonists, Platelet Aggregation Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Angiotensin-Converting Enzyme Inhibitors, Drug Therapy, Combination, Hospitalization, Proportional Hazards Models, Cohort Studies, Follow-Up Studies, Time Factors, Aged, Middle Aged, Female, Male, Acute Coronary Syndrome, Secondary Prevention, Angiotensin Receptor Antagonists