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

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


Purpose: 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.

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

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

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


  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors