Metaanalyses Comparing The Effects Of Acei Or Arb For Preventing The Development And Progression Of Diabetic Kidney Disease

Recently, several meta-analyses (66-69) comparing the effects of ACEi and ARB for preventing the development and progression of DN were published. Surprisingly, these reports reached totally different conclusions indicating the well known discrepancies between meta-analyses and subsequent large randomized, controlled trials (70). In 2004, Strippoli GF, et al. (66) analyzed 43 trials with a total of 7545 patients; 36 of 43 identified trials compared ACEi with placebo (4008 patients), 4 compared ARB with placebo (3331 patients), and 3 compared ACEi with ARB (206 patients). Both agents had similar effects on renal outcomes. ACEi significantly reduced all-cause mortality [risk reduction (RR) 0.79] compared with placebo but ARB did not (RR 0.99). In 2006 the Australian group reported two further detailed analyses (67,68). Based on one of these (67) they concluded that ACEi are the only agents with proven renal benefit in patients who have diabetes with no nephropathy and the only agents with proven survival benefit in patients who have diabetes with nephropathy. This statement was criticized (57) since they failed to take into account the possibility that their results could be explained by the fact that the majority of trials using ACEi were performed in relatively young patients (mean age 35 years) with type 1 diabetic nephropathy, whereas the treatment trials using ARB were performed mainly in patients with type 2 diabetic nephropathy (mean age 60 years). Thus, it could well be that the difference in CV events and mortality was driven by the population studied and not the therapeutic agent used (57). In their last Cochrane analysis (68, see Table 4) fifty studies (13,215 patients) were identified; 38 compared ACEi with placebo, 5 compared ARB with placebo and 7 compared ACEi and ARB directly. The effects of ACEi and ARB on renal outcomes (ESRD, doubling of creatinine, prevention of progression of micro- to macroalbuminuria, remission of micro- to normoalbuminuria) were similarly beneficial (Table 4). There was no significant difference in the risk of all-cause mortality for ACEi versus placebo (RR 0.91) and ARB versus placebo (RR 0.99). A subgroup analysis of studies using full-dose ACEi versus studies using half or less than half the maximum tolerable dose of ACEi showed a significant reduction in the risk of all-cause mortality with the use of full-dose ACEi (RR 0.78).

Another misleading meta-analysis was reported by Casas, et al. (69), which concluded that ACEi and ARB were no more effective than other antihypertensive drugs with respect to renoprotection. Serious questions have been raised regarding the validity (70,71) of the Casas report, which was primarily an analysis of the ALLHAT patient population (85% of all patients) rather than a meta-analysis. The ALLHAT study excluded patients with severe renal disease and neglected to measure proteinuria. In fact, there was no similarity between the patient populations in the ALLHAT trial when compared with the existing valid DN trials in the literature. The ALLHAT trial itself has been the subject of considerable controversy from many points of view. A secondary analysis by Rahman M, et al. (72) concluded that hypertensive patients with a reduced GFR who were entered into the ALLHAT trial were not protected from the development of ESRD by the use of lisinopril

TABLE 4 The Effects of ACEi and ARB on Renal Outcomes and All-Cause Mortality in Diabetic Patients

ACEi vs. placebo ARB vs. ACEi ARB vs. placebo

TABLE 4 The Effects of ACEi and ARB on Renal Outcomes and All-Cause Mortality in Diabetic Patients

ACEi vs. placebo ARB vs. ACEi ARB vs. placebo

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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