Intensive treatment of hypertension and hyperglycaemia in patients with type 2 diabetes

The findings of several recent epidemiological and clinical trials have suggested that higher levels of blood pressure and hyperglycaemia (or high glycated haemoglobin level) are associated with higher risk of macrovascular and microvascular complications in patients with type 2 diabetes. However, large clinical trials have shown that antihypertensive and hypoglycaemic treatment diminish the risk of myocardial infarction, stroke and end-stage renal disease. This is an important problem from a therapeutic point of view and the question is unanswered regarding the lowest blood pressure level and blood glucose level which we can safety reach without risk of arterial hypotension and hypoglycaemia. Two studies – ACCORD and ADVANCE – have sought answers to these questions. The ADVANCE trial had two parts: one part of the study evaluated the lowering of blood pressure using perindopril and indapamide, which added to previous therapy, and the second part of the study, in which all patients were required to receive sulfonylurea gliclazide treatments to reach glycated haemoglobin targets below 6.5%. In the ACCORD trial rosiglitazone was used in nearly all of the intensive therapy group to reach a mean glycated haemoglobin level below 6%. The ADVANCE study showed that antihypertensive treatment to achieve blood pressure reduction to a level of 134/75 mm Hg was associated with a 14% (p < 0.025) reduction in the relative risk of death from any cause in patients with diabetes and an 18% (p < 0.027) reduction in the relative risk of death from cardiovascular diseases. The ADVANCE trial reconfirmed the predicted reduction in cardiovascular events of about 14% (p < 0.02) and in new-onset microalbuminuria and nephropathy of about 21% (p < 0.001). The effect of intensive glucose-lowering treatment was reported to produce a relative reduction of 10% in the primary composite outcome of major macrovascular and a 21% reduction in nephropathy in comparison with the standard therapy group. In the ADVANCE trial, the intensive therapy group had a decreased, but not significantly, rate of death from cardiovascular disease and of death from any cause. In contrast in the ACCORD trial, the intensive therapy group had an increase in rate of death from any cause of about 22% and rate of death from cardiovascular causes of about 35%. In this paper we try to explain the differences in clinical outcomes in these two trials. Thus, neither study provides a definitive answer to the problem of glycaemic control. However, all patients with type 2 diabetes need antihypertensive and lipid-lowering therapy.