Risk Factor Control for Coronary Artery Disease Secondary Prevention in Large Randomized Trials

doi:10.1016/j.jacc.2013.01.044

Journal of the American College of Cardiology

Volume 61, Issue 15, 16 April 2013, Pages 1607-1615

https://doi.org/10.1016/j.jacc.2013.01.044 Get rights and content

Under an Elsevier user license

open archive

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)

Key Words

clinical trials

risk factor

secondary prevention

Abbreviations and Acronyms

CAD

coronary artery disease

diabetes mellitus

HbA1c

hemoglobin A1c

LDL-C

low-density lipoprotein cholesterol

OMT

optimal medical therapy

PCI

percutaneous coronary intervention

SBP

systolic blood pressure

Cited by (0)

: The COURAGE trial is supported by the Cooperative Studies Program of the United States Department of Veterans Affairs Office of Research and Development, in collaboration with the Canadian Institutes of Health Research, and by unrestricted research grants from Merck, Pfizer, Bristol-Myers Squibb, Fujisawa, Kos Pharmaceuticals, Datascope, AstraZeneca, Key Pharmaceutical, Sanofi-Aventis, First Horizon, and GE Healthcare, including in-kind support with Food and Drug Administration–approved drugs used by study participants. All industrial funding in support of the trial was directed through the United States Department of Veterans Affairs. The BARI 2D trial is supported by grants U01-HL061744, U01-HL061746, U01-HL061748, and U01-HL063804 from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases; and by GlaxoSmithKline, Lantheus Medical Imaging, Inc., Astellas Pharma US, Inc., Merck & Co., Inc., Abbott Laboratories, Inc., Pfizer, Inc., Abbott Laboratories Ltd., MediSense Products, Bayer Diagnostics, Becton Dickinson and Company, J.R. Carlson Labs, Centocor, Inc., Eli Lilly and Company, LipoScience, Inc., Novartis Pharmaceuticals Corporation, and Novo Nordisk, Inc. The FREEDOM trial is supported by U01 grants 01HL071988 and 01HL092989-01 from the National Heart, Lung, and Blood Institute. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the United States, the Department of Veterans Affairs, or the Canadian Institutes of Health Research. Dr. Farkouh received grant support from Eli Lilly and Sanofi-Aventis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.