New Metaanalysis On Bp Lowering

Recently, some major meta-analyses on the effect of blood-pressure lowering on major cardiovascular events and renal outcomes have been published (58-60). The principal messages from these important studies that are based upon randomized trials indicate that the main effect of blood-pressure lowering is in fact the blood-pressure lowering in itself, and not very much the specific method or type of blood pressure lowering. This is clearly the case for major cardiovascular events (58). The studies indicate that the benefits from ACE-inhibition or ARBs on renal outcomes in placebo-controlled trials probably result from an effective blood pressure lowering effect of these agents. The renal meta-analysis concludes (59) that in patients with diabetes, additional renal protection action of these substances beyond blood pressure remains unproven. It is, however, important to point out that lowering of urinary albumin concentration is seen with RAS-inhibition. This is considered as a positive effect seen in patients with diabetes as well as in patients without diabetes. A comparison between ACE-i and ARBs provides similar results in early nephropathy (60).

Regarding risk reduction of ESRD in clinical trials, the positive effect of blocking the RAS is clearly related to blood pressure. If the blood pressure is reduced by in mean 6.8 mmHg, there is a major benefit in using agents that block the RAS. With only a minor reduction of the blood pressure, the effect is almost neutral, suggesting that it is the blood pressure lowering per se associated with RAS inhibition that is important (58-61).

This clearly points to the old observation that increase of blood pressure is a major risk factor for progression of diabetic renal disease and that treatment of blood pressure reduces the later decline in GFR as well as development of ESRD (25). The use of ACE inhibitors and ARBs is thus beneficial by lowering BP. Argument against this concept has recently been discussed, but Casas et al. still argue that their study shows that there is an absence of evidence to support renoprotective effects of renin-angiotensin inhibitors independently of BP lowering; further studies may be needed, but difficult to conduct (59).

Blocking the RAS seems to have a beneficial effect by reducing the risk of type 2 diabetes (62,63). Outside nephropathy, the use of ACE inhibitors is clearly beneficial in diabetic patients with heart disease, commonly seen with nephropathy. However, the Diabetes REduction Approaches with ramipril and rosiglitazone Medications (DREAM) study did not confirm the effect of Ramipril on development of diabetes (64,65).

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