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Effect of Angiotensin-Converting Enzyme Inhibitors on the Progression of Nondiabetic Renal Disease: A Meta-Analysis of Randomized Trials

Ioannis Giatras, MD; Joseph Lau, MD; and Andrew S. Levey, MD
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For the Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group* From New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts. *For members of the Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group, see Appendix. Note added in proof: Since submission of the manuscript, the unpublished report by van Essen and colleagues has been published in abstract form (J Am Soc Nephrol. 1996; 7:1400), and a full-length article is in press (Kidney Int Suppl). In addition, a study by the GISEN group [16] has been published (Lancet. 1997; 349:1857-63); this study showed a beneficial effect of ramipril in nondiabetic renal disease. Including the GISEN group results in our meta-analysis does not substantially change the results. The pooled relative risks in the 11 studies are 0.69 (CI, 0.53 to 0.91) for end-stage renal disease and 1.32 (CI, 0.61 to 2.88) for death. Acknowledgments: The following companies provided support for the individual studies cited in these analyses: Merck Sharp & Dohme (Denmark, France, the Netherlands, and the United States), Merck & Co., Inc. (Australia). Roche AB (Sweden). Ciba-Geigy (Italy), and Bayer Australia. The authors thank Dr. John Ioannides, who assisted in statistical analysis. Grant Support: In part by awards R01 HS07782 and R01 HS08532 from the Agency for Health Care Policy and Research of the U.S. Public Health Service. Requests for Reprints: Andrew S. Levey. MD, Division of Nephrology, Department of Medicine, New England Medical Center, 750 Washington Street, NEMC# 391, Boston, MA 02111. Current Author Addresses: Drs. Levey and Giatras: Division of Nephrology, Department of Medicine, New England Medical Center, 750 Washington Street, NEMC# 391, Boston, MA 02111.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(5):337-345. doi:10.7326/0003-4819-127-5-199709010-00001
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Background: The effect of angiotensin-converting enzyme (ACE) inhibitors in slowing the decline in renal function in nondiabetic renal disease varies among studies.

Purpose: To use meta-analysis to assess the effect of ACE inhibitors on the development of end-stage renal disease caused by factors other than diabetes.

Data Sources: The English-language medical literature, identified by a MEDLINE search, and unpublished studies.

Study Selection: All randomized studies that compared ACE inhibitors with other antihypertensive agents and had at least 1 year of planned follow-up were selected. Studies of diabetic renal disease and renal transplants were excluded. A total of 1594 patients in 10 studies was included.

Data Extraction: Data on end-stage renal disease, death, drop out, and blood pressure were extracted. Study investigators confirmed results and provided additional data.

Data Synthesis: Among 806 patients receiving ACE inhibitors, 52 (6.4%) developed end-stage renal disease and 17 (2.1%) died; in the 788 controls, the respective values were 72 (9.1%) and 12 (1.5%). The pooled relative risks were 0.70 (95% CI, 0.51 to 0.97) for end-stage renal disease and 1.24 (CI, 0.55 to 2.83) for death; the studies were not significantly heterogeneous. The decreases in weighted mean systolic and diastolic blood pressures during follow-up were 4.9 and 1.2 mm Hg greater, respectively, in the patients who received ACE inhibitors.

Conclusions: Angiotensin-converting enzyme inhibitors are more effective than other antihypertensive agents in reducing the development of end-stage nondiabetic renal disease, and they do not increase mortality. It could not be determined whether this beneficial effect is due to the greater decline in blood pressure or to other effects of ACE inhibition.


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Figure 1.
Effect of anglotensin-converting enzyme (ACE) inhibition on risk for end-stage renal disease (ESRD) and death in patients with nondiabetic renal disease.PP

Data are the relative risk with 95% CIs on a logarithmic scale. The pooled relative risk for end-stage renal disease was 0.70 (95% CI, 0.51 to 0.97), indicating a significantly lower risk in the ACE inhibitor group. The result of the test for heterogeneity among studies was not significant ( < 0.75 and >0.2), indicating that the relative risk did not significant differ among studies. The pooled relative risk for death was not significant (1.24 [CI, 0.55 to 2.83]), and the result of the test for heterogeneity among studies was not significant ( > 0.2). The year of publication or approximate year of completion of the unpublished studies is given. Interrupted lines indicate that the CIs extend to infinity because no events occurred in these studies. * = Unpublished data provided by study investigators. AUS = Australia; DEN = Denmark; EUR = Europe; FR = France; HOL = the Netherlands; IT = Italy; SW, Sweden; USA = United States.

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