Hypertension in diabetes

Editor, – I refer to the article 'Hypertension in diabetes' (Aust Prescr 2002;25:8-10).

The author suggests that while AT₁ receptor antagonists may have the same benefits as ACE inhibitors, this has yet to be shown in clinical trials. I would draw your attention to the recently published PRIME program,^1,2 which evaluated the effects of irbesartan on morbidity and/or mortality in patients with hypertension and type 2 diabetes across the continuum of early and advanced stages of diabetic renal disease.

The PRIME program consisted of two trials, IRMA 2 and IDNT.

In IRMA 2, the irbesartan 300 mg group demonstrated a 70% relative risk reduction in the primary end-point of progression to overt proteinuria, compared with a control group (placebo in addition to other non-excluded antihypertensive therapies), p = 0.0004.¹

In IDNT, the primary end-point was the time until the first occurrence of doubling of serum creatinine, or end-stage renal disease, or all-cause mortality. The irbesartan group demonstrated:

• a 20% relative risk reduction in the primary end-point compared with the control group (placebo in addition to other non-excluded and antihypertensive therapies), p = 0.02
• a 23% relative risk reduction versus the amlodipine group, p = 0.006.²

In a recently updated position statement by the American Diabetes Association on diabetic nephropathy,³ the recommendation is that in treatment of albuminuria/nephropathy both ACE inhibitors and the AT₁ receptor antagonists can be used. The recommendations are as follows:

• in hypertensive and non-hypertensive type 1 diabetic patients with microalbuminuria or clinical albuminuria, ACE inhibitors are the initial treatment of choice
• in hypertensive type 2 diabetic patients with microalbuminuria or clinical albuminuria, AT₁ receptor antagonists are the initial drugs of choice.

While the AT₁ receptor antagonists are a newer class of drug, and data in the past have been limited, there is certainly a growing body of evidence such as PRIME on their use in hypertensive diabetic patients.

Victoria Elegant
Medical Director
Sanofi-Synthelabo Australia

Dr Julia Lowe, author of the article, comments:

I am grateful for the opportunity to comment on three studies which have evaluated the effects of AT₁ receptor antagonists on morbidity and/or mortality in patients with hypertension and diabetes. These studies were published after I had completed my article for Australian Prescriber and are concerned with patients who already have either microalbuminuria¹ or overt nephropathy.^2,4 My article was concerned solely with cardiovascular outcomes in patients with hypertension and diabetes, rather than the more specific question of patients who have already developed complications such as microalbuminuria or nephropathy. I note that none of these studies used an ACE inhibitor in the placebo group. Comparison with amlodipine in one of these trials² was interesting given the uncertainty about the value of calcium channel antagonists in prevention of diabetic nephropathy. Only the RENAAL trial of losartan addressed death as part of its composite primary outcome⁴ There was no difference in deaths in the losartan group (158/751) compared to controls in the placebo group (155/762). In the other two studies there was no difference in the number of deaths between groups, but the studies were not designed with sufficient power to detect a difference in deaths as an outcome.^1,2

In summary, I see no need to change the statement in my article that 'While AT₁ receptor antagonists may have the same benefits as ACE inhibitors, this has yet to be shown in clinical trials'.