AHA2015年会ACCORDION研究

• Urine protein <1.0 gm/24 hours or equivalent • Serum Creatinine <1.5 mg/dl
Cushman WC et al. Am J Cardiol. (2007)
ACCORD Double 2 x 2 Factorial Desig
• Two pre-specified secondary outcomes, non-fatal stroke (HR=0.63, p=0.03, 95% CI 0.41-0.96) and total stroke (HR=0.59, p=0.01, 95% CI 0.39-0.89), showed significant reductions that were consistent with other BP treatment trials. • Post-hoc analysis suggested that intensive BP or intensive glycemia treatment alone improved major CVD outcomes by 26% compared with combined standard treatment. There was, however, no additional benefit from combining the two intensive therapies.
William C. Cushman, MD, FACP, FAHA Veterans Affairs Medical Center, Memphis, TN Gregory W. Evans, MA Wake Forest School of Medicine, Winston-Salem, NC Jeffrey A. Cutler, MD, MPH, National Heart, Lung and Blood Institute, Bethesda, MD
P-value <0.001 0.40 <m Hg)
Diastolic BP (mm Hg HbA1c (%)
139 + 16
76 + 10 8.3 + 1.1
140 + 17
75 + 11 8.5 + 1.2
139 + 16
76 + 10 8.3 + 1.1
For The ACCORD/ACCORDION Study Group
Disclosure
William C. Cushman, MD, reports receiving institutional grant support from NHLBI/NIH, Eli Lilly, and Merck, and participating in uncompensated consulting for Takeda. Gregory W. Evans, MA, and Jeffrey A. Cutler, MD, MPH, report no conflicts to disclose.
Primary Outcome by Pre-defined Subgroups
Also examined DBP tertiles (p=0.16), HbA1c (p=21) and number of screening meds (p=0.31)
ACCORDION BP Conclusions
Cushman WC et al. Am J Cardiol. (2007)
ACCORD BP Trial Eligibility
• Stable Type 2 Diabetes >3 months • HbA1c 7.5% to 11% (or <9% if on more meds) • High CVD risk = clinical or subclinical disease or >2 risk factors • Age (limited to <80 years after Vanguard)
ACCORD BP Trial Results
• With an average follow-up of 4.7 years, the ACCORD BP Trial found a non-significant reduction in major CVD events (HR=0.88, p=0.20, 95% CI 0.73-1.06).
ACCORD BP Baseline Characteristics vs. Participation in Post-trial Follow-up
ACCORD (N=4733) Age (yrs) Female (%) Non-Hispanic White (%) Secondary Prevention (%) 62 + 7 48 59 34 Not Contributing Post-trial (N=776) 64 + 8 49 53 45 Contributing Post-trial (N=3957) 62 + 7 47 60 31
369 (2.0) 419 (1.9) 121 (0.6) 185 (1.0) 107 (0.6) 109 (0.6)
Standard Events (%/yr)
410 (2.2) 412 (1.9) 129 (0.6) 215 (1.1) 124 (0.6) 130 (0.7)
HR (95% CI)
0.03
0.03 <0.001
Values are % or Mean + SD
CVD Outcomes
median follow-up of 8.8 years
Intensive Events (%/yr)
Primary Total Mortality Cardiovascular Deaths Nonfatal MI Nonfatal Stroke Total Stroke
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)
Cushman et al, NEJM (2010) Margolis et al, Diabetes Care (2014)
ACCORDION BP
• 3957 (87%) surviving ACCORD BP Participants consented to post-trial follow-up of up to 60 months
0.91 (0.79,1.05) 1.04 (0.91,1.19) 0.96 (0.75,1.23) 0.87 (0.72,1.06) 0.88 (0.68,1.14) 0.85 (0.66,1.10)
P
0.19 0.59 0.74 0.16 0.32 0.22
Also examined Fatal/Nonfatal HF (HR=0.97, p=0.79), a composite of fatal coronary events, nonfatal MI and unstable angina (HR=0.93, p=0.30) and a composite of the primary outcome, revascularization and unstable angina (HR=0.98, p=0.64)
• In patients with T2DM at increased CV risk, 4.9 years of intensive BP lowering did not reduce the rate of a composite of fatal and non-fatal major CV events or mortality over a median follow-up of 8.8 years. • However, with long term follow-up, a significant interaction between BP and glycemia interventions was observed, with evidence of benefit for intensive BP lowering in participants randomized to standard glycemia therapy (HR=0.79, 95% CI 0.65 – 0.96). • The stroke benefit observed during the active intervention did not persist after BP differences waned. This finding adds evidence that the BP-stroke relationship observed during ACCORD was real.
• Primary outcome was a composite of CVD death, non-fatal MI and non-fatal stroke adjudicated by a blinded M&M committee • BP Trial randomized 4733 participants at 77 sites in US & Canada
• Time until first event after randomization • Participants who declined or died of non-CVD causes were censored as of the last date data were available.