Many guidelines recommend angiotensin-converting enzyme (ACE) inhibitors for patients with diabetes mellitus and increased urinary protein excretion, independent of presence or absence of hypertension (1). However, it has not so far been confirmed that ACE inhibitors have a specific protective effect independent of blood pressure on the cardiovascular and renal complications of these patients. The HOPE* trial and the associated MICRO-HOPE* subtrial of diabetes patients do not provide reliable answers. In this trial comparing 10 mg ramipril daily (DELIX etc.) with placebo the majority of patients was hypertensive, sometimes with heart failure and there are considerable blood pressure differences between the groups, which are sufficient to explain the clinical advantages that were found (a-t 2000; 31: 21-2 and a-t 2002; 33: 40-1).

A large study has now appeared, sponsored by Aventis and the French Health Ministry - DIABHYCAR* - of low-dose ramipril (1.25 mg/day) in patients with type 2 diabetes and pathological proteinuria (2). 4.912 normotensive (44%) and hypertensive (56%) patients with micro- (74%) or macroalbuminuria (26%) aged 65 years on average were included and followed up for a median of four years. The duration of diabetes was ten years on average, the HbA1c averaged 7.8% and the blood pressure averaged 145/82 mmHg. Ramipril reduced the blood pressure after two years by 2.4/1.1 mmHg compared to placebo. The ACE inhibitor tended to reduce the albuminuria, but had no effect on the primary endpoint, a combination of cardiovascular death, myocardial infarction, stroke, heart failure or renal failure. A primary event occurred in 14.8% of the patients in the ramipril group and in 15.3% in the placebo group. In the subgroup of patients who were normotensive at the start of the study, which might also include a few hypertensive patients because of the threshold for hypertension defined in the study (BP > 140/90; cf. WHO: BP >/= 140/90), 12.9% suffered a primary event on ramipril compared to 12.3% on placebo; in the hypertensive group, the results were 16.3% vs. 17.7%. Overall, 24.9% of patients on ramipril and 22.4% on placebo reported adverse effects that necessitated stopping the medication.

	ACE inhibition in patients with type 2 diabetes does not have a beneficial effect on cardiovascular and renal complications, despite a reduction in pathologically raised proteinuria.
	Treatment with ACE-inhibitors is unnecessary in patients with diabetes and normal blood pressure independent of the level of proteinuria and increases the rate of adverse effects.

(R = randomised study)

1

Deutsche Liga zur Bekämpfung des hohen Blutdrucks e.V.: Leitlinien für die Prävention, Erkennung, Diagnostik und Therapie der arteriellen Hypertonie [German League for Combatting High Blood Pressure: Guidelines for the prevention, identification, diagnosis and treatment of arterial hypertension]. Nov. 2003; http://www.uni-duesseldorf.de/WWW/AWMF/ll/ihypto01.htm#5.4 (accessed 4th March 2004)

2

MARRE, M. et al.: BMJ 2004; 328: 495-9

HOPE = Heart Outcomes Prevention Evaluation; MICRO-HOPE = microalbuminuria, cardiovascular and renal outcomes-HOPE