ACE inhibitors in type 2 diabetes with hypertension

Last reviewed 09/2021

The role of ACE inhibitors in patients with diabetics has been investigated in the studies such as the:

• HOPE study in diabetics
  • the HOPE study (n=9,297, 38% with diabetes) provided evidence that ramipril significantly reduced the risk of MI, stroke or cardiovascular death compared with placebo over five years (14.0% vs. 17.8%; NNT 27) - benefits were especially evident in the subgroup of patients with diabetes
  • it has been suggested that these effects of ramipril are beyond those that could be expected from its BP lowering properties - however, this has been disputed by meta-analyses that suggest, for most cardiovascular outcomes, BP lowering effects account for the majority of the benefits seen with different antihypertensives (1)

ACE inhibitors slow the progression of renal disease in type I diabetes independent of the effects of blood pressure. There is mounting evidence that the same is true in type II diabetes. The benefits of treatment with ACE inhibitors may result from reducing proteinuria and reducing blood pressure (these effects are not specific to ACE inhibitors) and via direct effects of angiotensin II on glomerular haemodynamics, inflammation, slcerosis and fibrosis (3).

Note it has been suggested that thiazide diuretics should be the first-line treatment for diabetic patients with hypertension based on study evidence such as ALLHAT (2) (see linked item):

• "..Thiazide diuretics are a suitable first choice in people with type 2 diabetes. ACE inhibitors are a reasonable alternative to a thiazide if these are unsuitable, or addition to a thiazide if further BP lowering is required. ACE inhibitors should be used first-line in people with type 2 diabetes if they have renal disease..."

A meta-analysis of the use of angiotensin receptor blockers as antihypertensive treatment for patients with diabetes mellitus concluded that (4):

• "...angiotensin receptor blockers failed to show significant reduction in total mortality and cardiovascular morbidity and mortality in diabetic patients. The only statistical benefit was the reduction of end-stage renal disease compared with placebo. Therefore, at this time angiotensin receptor blockers have not proved to be superior to standard anti-hypertensive treatment in diabetic patients.."

Reference:

1. Staessen JA, Wang J-G, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001;358:1305–15.
2. MeReC Briefing 2004;26:1-8.
3. Evidence-Based Medicine (January/February 2002), 7 (1), 13.
4. Siebenhofer A et al. Angiotensin receptor blockers as anti-hypertensive treatment for patients with diabetes mellitus: meta-analysis of controlled double-blind randomized trials. Diabet Med 2004;21:18-25.