Diminishing Returns in Cardiovascular Disease Research: Systematic Review and Meta-analysis

  • Author / Creator
    Barrington, Catherine
  • If “usual care” improves with time, it becomes increasingly difficult for new therapies to demonstrate additional benefit. Our objective then was to determine, by systematic review of randomized trials, whether the absolute cardiovascular risk reduction attributed to community-implemented preventive therapies has changed over time. Data sources included MEDLINE and Cochrane Central Register of Controlled Trials from inception until 31 December 2015. We examined randomized controlled trials focusing on primary or secondary prevention of atherosclerotic cardiovascular disease (myocardial infarction or stroke) published in 6 leading medical journals. Eligible studies examined a community-implemented intervention, had  1000 patient-years of observation, and a primary outcome that included at least one of: mortality (all-cause or cardiovascular), stroke, or myocardial infarction. Paired reviewers independently screened articles and extracted data. The period of eligible studies was broken into 9-year quintiles for analysis of time trends. The primary outcome was absolute risk reduction in all-cause mortality. We also examined absolute difference in cardiovascular mortality, stroke/TIA (transient ischemic attack), and myocardial infarction/acute coronary syndrome (MI/ACS).

    A total of 170 studies met the inclusion criteria. Absolute risk reduction for all-cause mortality fell steadily from 3.42 deaths per 100 patient-years in 1971-1979 to 0.16 deaths per 100 patient-years in 2007-2015. Similar falls were observed for absolute risk reduction in MI/ACS (5.42 to 0.37 deaths per 100 patient-years). Cardiovascular mortality (1.34 to 0.11 deaths per 100 patient-years), and stroke/TIA (1.51 to 0.05 deaths per 100 patient-years) showed similar falls from 1980-1988 to 2007-2015. This shows that the absolute additive benefit from new therapies targeting the prevention of atherosclerotic cardiovascular disease continues to diminish with time. As usual care improves, effective new therapeutics will face ever greater hurdles to demonstrating statistical and clinical significance.

  • Subjects / Keywords
  • Graduation date
    Fall 2019
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
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