DISCUSSION: Long-term Cardiovascular Effects of 4.9 Years of Intensive Blood Pressure Control in Type 2 Diabetes Mellitus: The Action to Control Cardiovascular Risk in Diabetes Follow-On Blood Pressure Study (ACCORDION)

GEORGE L. BAKRIS MD, FAHA, FASNPROFESSOR OF MEDICINEDIRECTOR ASH COMPREHENSIVE HYPERTENSION CENTERTHE UNIVERSITY OF CHICAGO MEDICINECHICAGO, IL USA

Main Questions1. How do the long term ACCORD results resonate

with other long term BP/ Glucose trials in diabetes2. How does these long term outcomes match with

the nondiabetic cohort of SPRINT

Trials That Randomized BP and Glycemic Control

Trials UKPDS ACCORD- glycemic

interaction VADT

Median HbA1c achievedIntensive –7.4%

Intensive -8.1% 6.3% (8 months)

Intensive –7.1%

UK Prospective Diabetes Study (UKPDS) Group (UKPDS 34). Lancet 1998;352:854 – 865, Holman RR, et.al. N Engl J Med 2008;359:1577-89.

CV Outcomes Sudden Death (higher in intensive glycemic

control groups of ACCORD, VADT and ADVANCE) No long term mortality benefit in intensive glycemic

control group of VADT CV events-in long term follow-up-BOTHADVANCE (median F/U-5.4 years) HR 0.88 (95% CI, 0.77 to 0.99; P = 0.04) major cardiovascular events per 1000 person-years)VADT (median F/U-9.8 years) absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years)

UKPDS (median F/U-7.8 years) overall intensive groups had 20% absolute risk reduction of death.

Is there a Legacy Effect on Outcomes from these trials?

Trials UKPDS ACCORD- glycemic

interaction VADT

Glucose BPYES No

?? No

?? ??Conclusion: Early reasonable glycemic control in natural history has extended benefits on CV outcomes where BP reduction does not unless sustained (UKPDS and ACCORD).

UK Prospective Diabetes Study (UKPDS) Group (UKPDS 34). Lancet 1998;352:854 – 865, Holman RR, et.al. N Engl J Med 2008;359:1577-89.

Standardized Associations Between 10–mm Hg Lower Systolic BP and All-Cause Mortality, Macrovascular Outcomes, and Microvascular

Outcomes in Patients with Diabetes

Emdin CA et.al. Blood Pressure Lowering in Type 2 Diabetes: A Systematic Review and Meta-analysis JAMA. 2015;313(6):603-615.

40 trials judged to be of low risk of bias (100 354 participants)

Perkovic V, Rodgers A. N Engl J Med 2015. DOI: 10.1056/NEJMe1513301

Outcomes from SPRINT and ACCORD Trials and Combined Data from Both Trials.

Summary ACCORDION supports the data that intensive

blood pressure control reduces the risk of stroke and in the absence of intensive glycemic control is associated lower CV risk.

The effects on individual outcomes in SPRINT and the ACCORD trial are generally consistent.

The main differences were ACCORD had less statistical power than SPRINT, and its primary outcome included a higher proportion of events that are less sensitive to blood-pressure reduction.

Compared to other BP/Glucose trials, the data from ACCORDION are consistent if you ignore the dramatic relative acute drop in glucose in ACCORD.