Comprehensive Cardiovascular Risk Factor Control Improves Survival: The BARI 2D Trial

Abstract

Background: It is unclear whether achieving multiple risk factor (RF) goals through protocol-guided intensive medical therapy is feasible or improves outcomes in type 2 diabetes mellitus.

Objectives: This study sought to quantify the relationship between achieved RF goals in the BARI 2D (Bypass Angioplasty Investigation Revascularization 2 Diabetes) trial and cardiovascular events/survival.

Methods: We performed a nonrandomized analysis of survival/cardiovascular events and control of 6 RFs (no smoking, non-high-density lipoprotein cholesterol <130 mg/dl, triglycerides <150 mg/dl, blood pressure [systolic <130 mm Hg; diastolic <80 mm Hg], glycosylated hemoglobin <7%) in BARI 2D. Cox models with time-varying number of RFs in control were adjusted for baseline number of RFs in control, clinical characteristics, and trial randomization assignments.

Results: In 2,265 patients (mean age 62 years, 29% women) followed up for 5 years, the mean ± SD number of RFs in control improved from 3.5 ± 1.4 at baseline to 4.2 ± 1.3 at 5 years (p < 0.0001). The number of RFs in control during the trial was strongly related to death (global p = 0.0010) and the composite of death, myocardial infarction, and stroke (global p = 0.0035) in fully adjusted models. Participants with 0 to 2 RFs in control during follow-up had a 2-fold higher risk of death (hazard ratio: 2.0; 95% confidence interval: 1.3 to 3.3; p = 0.0031) and a 1.7-fold higher risk of the composite endpoint (hazard ratio: 1.7; 95% confidence interval: 1.2 to 2.5; p = 0.0043), compared with those with 6 RFs in control.

Conclusions: Simultaneous control of multiple RFs through protocol-guided intensive medical therapy is feasible and relates to cardiovascular morbidity and mortality in patients with coronary disease and type 2 diabetes mellitus. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Keywords: blood pressure; cholesterol; coronary heart disease; diabetes mellitus; glycosylated hemoglobin A; smoking.

Figure 1. Distribution of the Number of RFs In Control: Baseline to Year 5

The numbers of RFs in control are shown at baseline and for each year of the trial. Over time, the proportion of participants with 4 or more RFs in control increased while the proportion with fewer RFs in control declined. RF = risk factor.

Figure 2. Hazard Associated With Individual RFs Out of Control/Out of Target Range

Multivariable-adjusted hazard ratios (95% CI) are shown for individual RFs out of target range. RFs in control/in target range for this exploratory analysis were defined as: non-HDL-C <130 mg/dl, TG <150 mg/dl, 110 mm Hg< SBP <140 mm Hg, DBP <80 mm Hg, 65%< HbA_1c <7.5%, nonsmoker. Cox models were adjusted for number of total lesions, abnormal LVEF, myocardial jeopardy index, history of prior revascularization, age, sex, race/ethnicity, country, and trial strata. DBP = diastolic blood pressure; HbA_1c = glycosylated hemoglobin; LVEF = left ventricular ejection fraction; MI = myocardial infarction; non-HDL-C = high-density lipoprotein cholesterol; RF = risk factor; SBP = systolic blood pressure; TG = triglycerides.

Central Illustration. Cardiac RF Control Improves Survival: Number of RFs in Control and Outcomes

The number of RFs in control is plotted against mortality (A and B) and against CVD events (C and D). In panels A and C, RFs in control are defined on the basis of the BARI 2D protocol (main analysis). A J-shape is evident: individuals with 6 RFs in control have a numerically higher risk of events than those with 5 RFs in control. In panels B and D, “optimal ranges” are defined for systolic and diastolic BP and HbA_1c. A J-shape is no longer evident and the risk gradient comparing 6 versus 0 to 2 RFs in control is steeper. BP = blood pressure; CVD = cardiovascular disease; HbA_1c = glycosylated hemoglobin; HR = hazard ratio; MI = myocardial infarction; RF = risk factor.