Intensified, multiplerisk factor intervention in patients with type 2 diabetes at high risk cuts cardiovascular events by half
Type 2 diabetes is a vascular disease characterised by a 2-6 fold increase in risk of cardiovascular disease and death and a life expectancy which in highrisk patients may be shortened by 5-10 years. Once diabetic patients have developed severe vascular complications the 5-years survivalrate is comparable with that of many malignant disorders. The epidemic growth worldwide in the incidence of type 2 diabetes and the severe vascular complications makes it an enormous burden to the individual and to the society.
During the last 10 years numerous prospective studies have, however, identified a series of potentially modifiable risk factors for ischaemic vascular complications. These factors include hyperglycaemia, hypertension, dyslipidaemia, microalbuminuria, a pro-thrombotic state, and smoking. Also, crucial information has been gained from singlerisk factor intervention trials in both diabetic and non-diabetic people. The degree of relative risk reduction with each individual risk factor target ranges from small (e.g., non-significant for hyperglycaemia lowering using insulin or sulfonylurea in the UKPDS), to moderate (e.g., about 10 % with aspirin therapy), to substantial (e.g., 25-30 % with blood pressure reduction or statin-induced lipid lowering).
Based on these trials many national diabetes associations recommend a multiplerisk factor intervention approach from the very clinical diagnosis of type 2 diabetes. The approach appears reasonable; yet, it involves considerable effort and expense on the part of the patient as well as the healthcare providers, and the efficacy of this ‘gold standard’ of a multifactorial therapy had until recently not been validated in an intervention trial.
We have published the results of the Steno-2 Study (initiated in 1992) which evaluated the pay-off of an integrated intensive behaviour modification and an intensive targeted and tailored polypharmacy in high-risk patients with type 2 diabetes and microalbuminuria. The results provide the abundant evidence that the combined, intensified treatment strategy is clearly superior to the conventional, multifactorial one.
After 7.8 years of intervention the primary endpoint was a composition of mortality from cardiovascular causes, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, non-fatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The results were remarkable: 44 % of patients in the conventional group had a cardiovascular event compared with 24 % in the intensive group; in other words, an absolute risk reduction of 20 % and a relative risk reduction of more than 50 %. Also, the curves representing time to first cardiovascular event for the two groups continued to diverge throughout the follow-up period suggesting an even greater effect on longterm treatment. Similarly, the relative risk of developing nephropathy, retinopathy, and autonomic neuropathy were all reduced by about 50 % in the intensively treated group.
Oluf Pedersen is the Principal Investigator of the Steno-2 study.
Papers based on the Steno-2 study:
1. Gæde P, Vedel P, Parving H-H, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria: the Steno type 2 randomised study. Lancet 353: 617-622, 1999.
2. Gæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348: 383-393, 2003.
3. Pedersen O, Gæde PH: Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2-study. Metabolism 52: 19-23, 2003.
4. Gæde P, Tarnov L, Vedel P, Parving H-H, Pedersen O. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 19: 2784-2788, 2004.
5. Gæde P, Pedersen O: Intensive integrated therapy of type 2 diabetes: implications for long-term prognosis. Diabetes 53 (suppl 3): S39-S47, 2004.
6. Gæde P, Pedersen O: Target intervention against multiple risk markers to reduce cardiovascular disease in patients with type 2 diabetes. Ann Med 36: 355-366, 2004.
7. Gæde P, Hildebrandt P, Hess G, Parving H-H, Pedersen O: Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. Diabetologia 48: 156-163, 2005.
8. Gæde P, Pedersen O: Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk: what are we waiting for? Horm Metab Res 37 (suppl 1): 76-82, 2005.