ADVANCE - Type 2 diabetes - vascular risk with intervention

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  • 21% relative risk reduction in risk of new or worsening nephropathy
  • ADVANCE - Type 2 diabetes - vascular risk with intervention

    1. 1. Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes N Eng J Med 358;24 2560 - 2572 ADVANCE Collaborative Group Taz Babiker
    2. 2. Population  Patients with type 2 diabetes aged ≥ 30 years at diagnosis  Aged ≥ 55  History of major macrovascular disease, OR  At least one other risk factor for vascular disease  Excluded if:  Definite indication for any of the study treatments  Contraindication to any of the study treatments  Definite indication for long-term insulin  Median duration of follow up 5.0 years
    3. 3. Intervention  6 week run in period  Fixed combination of perindopril and indapamide  Random assignment to either perindopril or indapamide or placebo  Random assignment to intensive (HbA1c < 6.5%) vs standard glucose control  Gliclazide MR ± metformin, thiazolidinediones, acarbose or insulin  Regular follow up
    4. 4. Comparison If standard glucose control, discontinued gliclazide and switched to different SU if required
    5. 5. Outcome  Primary outcomes – composite of macrovascular and microvascular events  Death from cardiovascular causes  Nonfatal MI  Nonfatal stroke  New or worsening nephropathy  Doubling of serum creatinine  Renal replacement therapy  Death due to renal disease  Retinopathy
    6. 6. Outcome HbA1c 6.5% vs 7.3% ?significant Systolic BP 135.5 vs 137.9 mmHg (p<0.001) Weight 0.7 kg greater in intensive group (p<0.001) Major macro/microvascular event: 18.1 vs 20.0% (hazard ratio 0.90, p=0.01) In a 5 yr period, an event would be averted in 1 in 52 participants Sig reduction in major microvascular but not major macrovascular events No evidence of interaction between BP and glucose intervention
    7. 7. Outcome Death: 8.9% vs 9.6% (p=0.28) Reduction in renal events  new/worsening nephropathy (HR 0.79, p=0.006)  New-onset microalbuminuria (HR 0.91, p=0.02)  Macroalbuminuria 2.9% vs 4.1% (HR 0.70, p<0.001)  Reduced RRT or death from renal causes – 0.4% vs 0.6%, HR 0.64, p=0.09)  Increased severe hypoglycaemia (BM < 2.8) and minor hypos in intensive group
    8. 8. Discussion  ACCORD – excess mortality in intensive arm led to premature termination  ADVANCE – no sig difference in mortality from any cause/CV causes  Not enough statistical power to achieve expected improvement in CV risk with intensive group  Lower BP explains some but no more than 25-33% of the relative risk reduction

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