The diabetes epidemic continues to grow unabated, with a staggering toll in micro- and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of
cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant
hypertension doubles total mortality and
stroke risk, triples the risk of
coronary heart disease and significantly hastens the progression of microvascular complications, including
diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful
antihypertensive treatment will often require a combination
therapy, either with separate drugs or with fixed-dose combinations.
Angiotensin converting enzyme (
ACE) inhibitor plus
diuretic combination
therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to
diuretic therapy and reduces the risk of
electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects.
ACE inhibitor plus
calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce
proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an
ACE inhibitor/
calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different
ACE inhibitor combinations in the treatment of patients with
type 2 diabetes mellitus and
hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH.