Antihypertensive treatment in patients with type-2 diabetes mellitus: what guidance from recent controlled randomized trials?

BACKGROUND: Patients with type-2 diabetes have a high prevalence of hypertension and show an elevated incidence of cardiovascular events and nephropathy.
OBJECTIVES: Recent randomized trials of antihypertensive therapy providing information about cardiovascular and renal risk in diabetes, blood pressure goals and best suitable drugs were reviewed.
FINDINGS: Evidence that association of type-2 diabetes with hypertension markedly increases cardiovascular and renal risk is incontrovertible: even blood pressure values in the high-normal range represent a more relevant risk than in non-diabetics. More versus less intensive blood pressure lowering or active versus placebo treatment can significantly prevent cardiovascular and renal events, with a particularly consistent reduction of proteinuria and microalbuminuria. Although several of the trials showing significant reduction of cardiovascular or renal risk achieved diastolic blood pressure (DBP) between 75 and 82 mmHg, systolic blood pressure (SBP) 140 mmHg was never achieved in trials showing cardiovascular benefits and SBP 130 mmHg was only achieved in two trials in normotensive subjects showing proteinuria reduction. The recommendation given by all major guidelines to lower SBP 130 mmHg appears to be difficult to comply with. Evidence of the superiority or inferiority of different drug classes (angiotensin-converting enzyme inhibitors, calcium antagonists, diuretics and beta-blockers) is rather vague, especially for cardiovascular protection. As to angiotensin-receptor antagonists, losartan has shown significant cardiovascular protection over a beta-blocker, and irbesartan, although not showing cardiovascular benefits over a calcium antagonist, was significantly better in retarding renal dysfunction and failure.
CONCLUSIONS: In most trials on hypertensive diabetics, the large majority of patients were on two, three and even four-drug therapy. Therefore, it appears reasonable that all effective and well tolerated antihypertensive agents can be used in association to achieve DBP 80 mmHg and, whenever possible, SBP 130 or 135 mmHg, with the regular inclusion of an angiotensin-receptor antagonist for its proven renoprotective action. Hopefully, better guidance will be provided by further trials.