Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data

TH Jafar, CH Schmid, M Landa, I Giatras… - Annals of internal …, 2001 - acpjournals.org
TH Jafar, CH Schmid, M Landa, I Giatras, R Toto, G Remuzzi, G Maschio, BM Brenner…
Annals of internal medicine, 2001acpjournals.org
Purpose: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal
disease. Data Sources: 11 randomized, controlled trials comparing the efficacy of
antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE
inhibitors in predominantly nondiabetic renal disease. Study Selection: Studies were
identified by searching the MEDLINE database for English-language studies evaluating the
effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE …
Purpose
To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease.
Data Sources
11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease.
Study Selection
Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997.
Data Extraction
Data on 1860 nondiabetic patients were analyzed.
Data Synthesis
Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d.
Conclusion
Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.
*For other members of the ACE Inhibition in Progressive Renal Disease Study Group, see Appendix 1.
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