Risk factor control for coronary artery disease secondary prevention in large randomized trials

J Am Coll Cardiol. 2013 Apr 16;61(15):1607-15. doi: 10.1016/j.jacc.2013.01.044.


Objectives: This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD).

Background: Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing.

Methods: We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment.

Results: The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up.

Conclusions: A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / methods
  • Cardiovascular Agents / therapeutic use
  • Cholesterol, LDL / blood
  • Comorbidity
  • Coronary Artery Bypass / methods
  • Coronary Artery Disease* / blood
  • Coronary Artery Disease* / epidemiology
  • Coronary Artery Disease* / prevention & control
  • Coronary Artery Disease* / psychology
  • Coronary Artery Disease* / therapy
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / therapy
  • Effect Modifier, Epidemiologic
  • Female
  • Glycated Hemoglobin / analysis*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Outcome and Process Assessment, Health Care
  • Practice Guidelines as Topic
  • Risk Factors
  • Risk Reduction Behavior
  • Secondary Prevention / methods*
  • Smoking Cessation


  • Cardiovascular Agents
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents

Associated data

  • ClinicalTrials.gov/NCT00006305
  • ClinicalTrials.gov/NCT00007657
  • ClinicalTrials.gov/NCT00086450