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Action to Control Cardiovascular Risk in Diabetes (ACCORD trial)

Study characteristics: - 10,251 adults with type 2 diabetes at high risk for cardiovascular disease - ACCORD lipid study: a) 5000 diabetics with hemoglobin A1c >= 7.5% b) mean age 62 years - ACCORD blood pressure study: a) 4733 diabetics, mean age 62 years, 48% women b) hemoglobin A1c >= 7.5% c) systolic blood pressure 130-180 mm Hg d) on <= 3 antihypertensive agents e) no proteinuria Treatment groups: - glycemic control two strategies: a) treatment to intensively lower blood glucose below 6.0% b) standard treatment - lipid study: - fenofibrate 160 mg QD vs placebo - all participants received simvastatin - ACCORD blood pressure study a) systolic blood pressure target < 120 mm Hg, vs b) systolic blood pressure target < 140 mm Hg (standard therapy for non diabeitcs) c) mean follow-up 4.7 years d) lower BP in the intensive-care group was achieved by prescribing more drugs in every antihypertensive class Results: - glycemic control: - intensive treatment arm ended early because of more deaths in that group 257 vs 203 of an excess of 3/1000/year - reasons for this are unclear - no particular pharmaceutical agent was implicated - no benefit for intensive glucose control in patients with long-standing diabetes mellitus type 2 [6] - fewer non-fatal acute coronary events despite higher cardiovascular & all-cause mortality [7] - lipid study - mean LDL cholesterol dropped 20 mg/dL (both groups) - mean HDL cholesterol increased 3.2 mg/dL (fenofibrate) vs 1.5 mg/dL (placebo) - median serum triglycerides decreased 41 mg/dL (fenofibrate) vs 17 mg/dL (placebo) - adverse cardiovascular events similar in 2 lipid groups 2.2% vs 2.4% - more adverse effects in women assigned to fenofibrate group - fenofibrate group was significantly more likely to leave study because of a decrease in glomerular filtration rate (GFR) 2.4% vs 1.1% [2] - ACCORD blood pressure study - mean number of antihypertensive agents at 1 year was 3.1 in the intensive care group vs 2.1 in the standard care group - no difference in cardiovascular mortality - annual rates of all-cause mortality was hight in the intensive care group 1.28% vs 1.19% in the standard care group [3] - adverse cardiovascular events was 1.9% in the intensive care group vs 2.1% in the standard care group, a non-significant difference - stroke was significantly lower in the intensive care group 0.32% vs 0.53% - serious adverse effects were significantly higher in the intensive care group - 3.3% vs 1.3% attributed to antihypertensive agents - more decrements in renal function - more episodes of syncope, bradycardia, hyperkalemia, hypotension - intensive blood pressure control does not slow progression of retinopathy in diabetics [4,5] - microvascular outcomes [4] - intensive glycemic control did NOT slow - end-stage renal disease - rise of serum creatinine to >3.3 mg/dL, or - need for photocoagulation or vitrectomy to treat retinopathy - ACCORD retinopathy study [4,5] - combination of intense glycemic control plus lipid control appeared to reduce progression of retinopathy, but editorialist notes findings not straightfoward [4] Notes: - increased mortality associated with intensive glycemic control trumps any benefit in reduction of microvascular complications

Related

ADVANCE trial diabetes mellitus type 2 (insulin-resistant)

General

clinical trial

References

  1. Canadian Diabetes Assocatiation http://www.diabetes.ca/section_main/newsreleases.asp?ID=210
  2. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74 PMID: 20228404 http://dx.doi.org/10.1056/NEJMoa1001282
  3. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. Epub 2010 Mar 14. PMID: 20228401 http://dx.doi.org/10.1056/NEJMoa1001286
  4. Ismail-Beigi F et al Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial The Lancet, Early Online Publication, 29 June 2010 PMID: 20594588 doi:10.1016/S0140-6736(10)60576-4 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960576-4/abstract
  5. The ACCORD Study Group and ACCORD Eye Study Group Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes N Eng J Med June 29, 2010 PMID: 20587587 http://content.nejm.org/cgi/content/full/NEJMoa1001288 - Klein BEK Reduction in Risk of Progression of Diabetic Retinopathy N Eng J Med June 29, 2010 PMID: 20587586 http://content.nejm.org/cgi/content/full/NEJMe1005667
  6. The ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011 Mar 3; 364:818 PMID: 21366473 http://www.nejm.org/doi/full/10.1056/NEJMoa1006524
  7. Gerstein HC et al. Effects of intensive glycaemic control on ischaemic heart disease: Analysis of data from the randomised, controlled ACCORD trial. Lancet 2014 Aug 1 PMID: 25088437