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Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.38237.585000.7C (Published 07 October 2004) Cite this as: BMJ 2004;329:828

ACEI vs. ARB in Diabetic Nephropathy: The Evidence

Sirs

The meta-analysis reported by Strippoli et al. provides a valuable
summary of published studies that have examined the potential benefits of
angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor
blockers (ARB) in patients with diabetic nephropathy (1). Unfortunately
we feel that the report is misleading in some respects and that two of its
conclusions are not fully supported by the data. We believe that these
matters should be clarified as the results of large meta-analyses are
frequently taken at face value and used to inform clinical guidelines.

It is stated that ACEI and ARB have equivalent effects on renal
outcomes. While it is true that published evidence indicates that ACEI
and ARB have equivalent anti-proteinuric effects (Figs 4,5,7,8), questions
remain over the relative efficacy of ACEI vs. ARB treatment in preserving
renal function in patients with established diabetic nephropathy. The
authors’ own analysis clearly shows that there is evidence for a
statistically significant benefit of ARB treatment on outcomes of doubling
of serum creatinine and incidence of end-stage renal disease (Fig 6). On
the other hand, a trend for benefit with ACEI treatment was not
statistically significant (Fig 3). Furthermore, it should be noted that
the only large randomised study to show a renal protective benefit (with
respect to doubling of serum creatinine) associated with ACEI treatment
was conducted in patients with type 1 diabetes mellitus (2). Only one
small study in patients with type 2 diabetes showed such benefit with ACEI
treatment and this study recruited only patients with microalbuminuria and
not established diabetic nephropathy (3). In our view a more accurate
summary of available data with respect to renal protection is:

1. There is substantial evidence of the antiproteinuric effects of
ACEI and ARB therapy in patients with type 1 and 2 diabetes mellitus and
microalbuminuria.

2. There is clear evidence that ACEI treatment slows the rate of
decline in renal function in patients with type 1 diabetes and established
diabetic nephropathy (2).

3. There is clear evidence that ARB treatment slows the rate of
decline in renal function in patients with type 2 diabetes and established
diabetic nephropathy (4,5).

The benefit on mortality ascribed to ACEI treatment is derived
entirely from the data of the MICRO-HOPE Study (6). It should be noted
that patients with established diabetic nephropathy were excluded form
this study and only patients of 55 years or older were included. The
MICRO-HOPE Study therefore shows a mortality benefit with ACEI treatment
in type 2 diabetic patients at increased risk for cardiovascular disease
but without established diabetic nephropathy. These findings cannot
necessarily be generalised to apply to all patients with diabetic
nephropathy as suggested in the article. Indeed, the study that showed
renal protective benefit with ACEI treatment in patients with type 1
diabetes failed to show any mortality benefit (2).

In choosing between ACEI and ARB therapy for patients with type 2
diabetes diabetic nephropathy, clinicians have to consider evidence of
proven renal protective benefit for ARB treatment versus evidence of a
mortality benefit for ACEI treatment (shown in patients without
established diabetic nephropathy). We agree entirely with the authors of
this and other reports that randomised controlled trials that compare
directly ACEI and ARB treatment in a homogeneous population of patients
are required to clarify the relative importance of these issues. Until
such data become available it seems reasonable to recommend the use of
either ACEI or ARB treatment for patients with type 2 diabetes mellitus
and diabetic nephropathy and ACEI treatment as first-line therapy in
patients with type 1 diabetes and diabetic nephropathy.

1. Strippoli GFM, Craig M, Deeks JJ, Schena FP, Craig JC. Effects of
angiotensin converting enzyme inhibitors and angiotensin II receptor
antagonists on mortality and renal outcomes in diabetic nephropathy:
systemic review. BMJ 2004;329:828-831.

2. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of
angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J
Med 1993;329:1456-1462.

3. Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M. Long-term
stabilizing effect of angiotensin-converting enzyme inhibition on plasma
creatinine and on proteinuria in normotensive type II diabetic patients.
Ann Intern Med 1993;118(8):577-81.

4. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH,
et al. Effects of losartan on renal and cardiovascular outcomes in
patients with type 2 diabetes and nephropathy. New Engl J Med
2001;345(12):861-9.

5. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et
al. Renoprotective effect of the angiotensin-receptor antagonist
irbesartan in patients with nephropathy due to type 2 diabetes. New Engl J
Med 2001;345(12):851-60.

6. The HOPE Study Investigators. Effects of ramipril on
cardiovascular and microvascular outcomes in people with diabetes
mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet
2000;355(9200):253-9.

Competing interests:
MWT has received research funding from Bristol-Myers Squibb

Competing interests: No competing interests

15 October 2004
Maarten W. Taal
Consultant Renal Physician
Christopher W. McIntyre, Richard J. Fluck
Derby City General Hospital, Uttoxeter Road, Derby, DE22 3NE