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

Bittner V, Bertolet M, Barraza Felix R et al.,
J Am Coll Cardiol. 2015;66(7):765-773. doi:10.1016/j.jacc.2015.06.019
 

Background

The effect of simultaneous control of multiple risk factors (RFs) on cardiovascular (CV) outcomes in type 2 diabetes mellitus (T2DM) populations has not been thoroughly investigated.
Data of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial were used to test the hypothesis that achievement of multiple RF goals through protocol-guided intensive medical therapy is feasible and associated with improved survival and lower CV event rates among patients with coronary heart disease (CHD) and T2DM [1-3].
CV RF management followed a protocol [3] addressing monitoring and regular feedback on smoking cessation, dietary and exercise advice, protocol-guided pharmacological management for dyslipidaemia, hyperglycaemia and hypertension. RF information was available for all 6 RFs in 47044 patients enrolled in BARI 2D. Patients were followed up until their 6-year visit (mean follow-up: 5.0+1.4 years).
 

Main results

• Only 7% of patients met all RF goals.
• The largest changes in medication use were seen within the first year.
• At baseline, on average 3.5 + 1.4 RFs were in control, which increased to 4.2+1.3 after 5 years (P<0.0001). At 5 years, >74% of patients had >4 RFs in control, and 15% achieved control of all 6 RFs.
• While there was no significant relationship between the number of RFs in control at baseline and subsequent death or CVD events, patients with 0-2 RFs in control at 1 year had twice and 1.7 times higher respective risks as compared with participants with all RFs in control.
• Over the course of the trial, the model suggested a J-shape, with patients with 6 RFs in control having a nonsignificantly higher risk of death and the composite endpoint than patients with 5 RFs in control.  
• In an exploratory analysis to examine potential harms of intensive BP and glucose control, HRs were calculated as a function of number of RFs in control, with systolic BP and HbA1c ranges modified to reflect less stringent control. The higher risk with 6 RFs as compared with 5 RFs was nog longer evident.
• Smoking, high non-HDL-c, systolic BP (too low) and HbA1c (too high) were significant RFs for death when assessing the adjusted effect of individual time-varying RF control status. High non-HDL-c and systolic BP outside the target range were significant predictors for CVD events.
   

Conclusion

While treatment targets are often not attained, BARI 2D data show that RF treatment goals are achievable by using evidence-based, protocol-guided therapy with dedicated personnel. These observational data suggest that patients with T2DM and CHD require multiple RF interventions, to positively affect survival and future clinical events.
Exploratory analyses suggested that aggressive control of systolic BP or HbA1c may be associated with increased risk, thus both undertreatment and overtreatment should be avoided.
 

Editorial comment [4]

Bittner et al. used “a creative method to evaluate the relationship between risk factor control, survival, and the composite endpoint of death, MI, or stroke, despite the absence of a no-OMT control group”, by assessing the relationship between the degree of risk factor goal attainment success and clinical outcomes.
“The present analysis showed that when multiple risk factor goals were achieved in diabetic
patients with stable ischaemic heart disease, survival was improved and cardiovascular events were reduced, but control of all 6 treatment targets was achieved in only a minority of patients.” (…) “The
remarkable observation in the present report is the significantly better survival (a 50% lower mortality rate) among patients who achieved good risk factor control in a trial that found no survival benefit from revascularization. Although the study was not a randomized comparison of OMT versus no OMT, the conclusions are convincing and consistent with evidence from decades of careful epidemiological research.” (…) “OMT needs to be more widely embraced and utilized by clinicians as both a best medical practice and a universal standard of care in all patients with coronary artery disease.”
 
Find this article online at JACC
 

References

1. Brooks MM, Frye RL, Genuth S, et al., for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial Investigators. Hypotheses, design, and methods for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). Trial. Am J Cardiol 2006;97:9G-19.
2. BARI 2D Study Group, Frye RL, August P, et al. A randomized trial of therapies for type 2 diabetes
and coronary artery disease. N Engl J Med 2009; 360:2503-15.
3.Albu J, Gottlieb SH, August P, et al., for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial Investigators. Modifications of coronary risk factors. Am J Cardiol 2006;97:41G–52
4. Maron DJ, Boden WE. Why Optimal Medical Therapy Should Be a Universal Standard of Care. J Am Coll Cardiol. 2015 Aug 18;66(7):774-6. doi: 10.1016/j.jacc.2015.06.018.