LETTER
Angiotensin-Converting Enzyme Inhibitors in Nondiabetic Renal Disease
Romulo E. Colindres, MD, and
Abhijik V. Kshirsagar, MD
15 April 1998 | Volume 128 Issue 8 | Page 694
TO THE EDITOR:
Giatras and colleagues recently conducted a thorough meta-analysis of the influence of angiotensin-converting enzyme (ACE) inhibitors in slowing the progression of nondiabetic renal disease [1]. They found that in the aggregate, ACE inhibitors reduce the risk for end-stage renal disease. The pooled relative risk of ACE inhibitors for this disease compared with control medications is 0.70 (95% CI, 0.51 to 0.97). The influence of blood pressure (initial and change at follow-up) on the observed effects could not be precisely assessed.
The study has important methodologic strengths that increase the validity of the findings. First, the authors included unpublished studies; this may greatly reduce the most important bias of meta-analysis, publication bias. Second, the authors verified data with authors of each individual study used in their analysis. Furthermore, it is reassuring that there is general concordance between the findings of the meta-analysis and those of the largest clinical trial [2]. Concerns about important differences between large clinical trials and meta-analyses have recently been raised [3, 4].
We have one concern about the conclusion of the meta-analysis. The authors state that "Angiotensin-converting enzyme inhibitors are more effective than other antihypertensive agents in reducing the development of end-stage nondiabetic renal disease." Our conclusion is that ACE inhibitors are more effective than other antihypertensive agents or placebo. The studies used by Giatras and colleagues in their meta-analysis have important clinical heterogeneity. Five of the 10 studies used other anti-hypertensive medicines, and 4 used placebo; for the other study, the control is unspecified. Thus, 436 of the 788 patients in the control group were assigned to placebo, and the rest were assigned to various antihypertensive agents. The test of heterogeneity assesses statistical differences in outcomes, and the random-effects model statistically allows for interstudy variability. Neither method may sufficiently control for clinical heterogeneity [5].
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Author and Article Information
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University of North Carolina at Chapel Hill; Chapel Hill, NC 27599
1. Giatras I, Lau J, Levey AS. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Ann Intern Med. 1997; 127:337-45.
2. Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med. 1996; 334:939-45.
3. LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med. 1997; 337:536-42.
4. Capparelleri JC, Ioannidis JP, Schmid CH, de Ferranti SD, Aubert M, Chalmers TC, et al. Large trials vs meta-analysis of smaller trials: how do their results compare? JAMA. 1996; 276:332-8.
5. Thompson SG. Why sources of heterogeneity in meta-analysis should be investigated. BMJ. 1994; 309:1351-5.
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