Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and/or Peripheral Arterial Disease

  • Ariel BergerEmail author
  • Alex Simpson
  • Nicholas Leeper
  • Brian Murphy
  • Beth Nordstrom
  • Windsor Ting
  • Qi Zhao
  • Jeffrey Berger
Original Research



Collectively, coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent and are associated with increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Improved ability to identify those at highest risk of these events may help optimize secondary prevention efforts in this population.


Using the Optum Integrated Database, a healthcare claims database linked to electronic medical records (EMR), we identified patients with CAD and/or PAD between January 1, 2009, and September 30, 2016. Index date was the earliest date on which chronic and stable disease was established. Follow-up ran from index date until earliest of patient death, plan disenrollment, or end of study. We developed multivariate Cox proportional hazards models to identify predictors of MACE and/or MALE, limited to measures presumed available to clinicians during patient encounters (e.g., age, presence of selected comorbidities).


A total of 20,932 patients met all selection criteria; 86.9% had CAD and 26.1% had PAD; 13% (n = 2753) experienced MACE and/or MALE during a mean follow-up of 2.3 years, for a rate of 7.1 events per 100 person-years (PYs). We identified 11 predictors of MACE and/or MALE. Most (95.1%) patients had ≥ 1 predictors; 34.0% and 6.9% had ≥ 4 and ≥ 6, respectively. Incidence of MACE and/or MALE was strongly correlated with number of predictors (r2 = 0.98), ranging from 2.3 per 100 PYs among those without predictors (4.9% of patients) to 18.7 per 100 PYs among those with ≥ 6 (6.9%). Patients with ≥ 1 predictor experienced 7.4 MACE and/or MALE per 100 PYs.


Readily identifiable predictors can be used to identify subgroups with chronic CAD and/or PAD at elevated risk of MACE and/or MALE. Further research is required to understand the degree to which these subgroups may benefit from early identification and treatment with secondary prevention therapies.


Janssen Pharmaceuticals.


Coronary artery disease Incidence Major adverse cardiovascular events (MACE) Major adverse limb events (MALE) Peripheral arterial disease Predictors 




This work was sponsored by Janssen Pharmaceuticals who were responsible for financing the study and the decision to publish the findings. The journal’s Rapid Service Fee was funded by Janssen Pharmaceuticals.

Editorial Assistance

We thank Sean Smith of Evidera for his editorial assistance in the development of this manuscript. This assistance was funded by Janssen Pharmaceuticals.


All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.


Ariel Berger is employed by Evidera, a research and consulting company to the biopharma industry. In this salaried position, he works with a variety of companies and organizations and is precluded from receiving payment or honoraria directly from these organizations for services rendered. Brian Murphy is employed by Evidera, a research and consulting company to the biopharma industry. In this salaried position, he works with a variety of companies and organizations and is precluded from receiving payment or honoraria directly from these organizations for services rendered. Beth Nordstrom is employed by Evidera, a research and consulting company to the biopharma industry. In this salaried position, she works with a variety of companies and organizations and is precluded from receiving payment or honoraria directly from these organizations for services rendered. Nicholas Leeper reports other modest research support from Bayer and Janssen. Windsor Ting reports a modest research grant from Janssen. Jeffrey Berger reports other modest research support from Janssen and AstraZeneca. Qi Zhao is currently employed at Eisai, Woodcliff Lake, NJ, USA. Alex Simpson was an employee of Evidera at the time research was conducted.

Compliance with Ethics Guidelines

This was a retrospective database study that used only completely de-identified data. Accordingly, institutional review board approval and informed consent were neither required nor sought.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available because of being “work for hire,” but are available from the corresponding author on reasonable request.


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Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Ariel Berger
    • 1
    Email author
  • Alex Simpson
    • 2
  • Nicholas Leeper
    • 3
  • Brian Murphy
    • 1
  • Beth Nordstrom
    • 1
  • Windsor Ting
    • 4
  • Qi Zhao
    • 5
  • Jeffrey Berger
    • 6
  1. 1.EvideraWalthamUSA
  2. 2.EvideraLondonUK
  3. 3.Stanford University Medical SchoolStanfordUSA
  4. 4.Mount Sinai Health SystemNew YorkUSA
  5. 5.Janssen PharmaceuticalsRaritanUSA
  6. 6.Center for the Prevention of Cardiovascular DiseaseNew York University School of MedicineNew YorkUSA

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