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Long-term progression of chronic renal insufficiency in the AIPRI Extension Study. The Angiotensin-Converting-Enzyme
F Locatelli1, I R Carbarns, G Maschio
1Divisione di Nefrologia, Ospedale di Lecco, Italy.
Insights
Benazepril, an ACE inhibitor, demonstrated long-term protection against chronic renal insufficiency (CRI) progression. Despite initial mortality imbalances, the extension study confirmed benazepril
Area of Science:
- Nephrology
- Pharmacology
- Clinical Trials
Background:
- The Angiotensin-converting-enzyme Inhibition on Progressive Renal Insufficiency (AIPRI) Study investigated benazepril's effect on chronic renal insufficiency (CRI).
- An unexpected mortality imbalance in the core study necessitated a follow-up extension.
Purpose of the Study:
- To evaluate the long-term effects of benazepril on CRI progression and mortality.
- To analyze patient outcomes from the AIPRI core study through an extension phase.
Main Methods:
- A post hoc data collection approach was used for the extension study.
- Patients were treated per investigators' usual practices, with a new primary endpoint: time to dialysis, renal transplantation, or renal death.
- Serum creatinine levels and all-cause mortality were also monitored.
Main Results:
- In an intention-to-treat analysis of core and extension data, fewer benazepril patients (79/300) experienced the composite endpoint compared to placebo patients (102/283) (P < 0.013).
- The initial mortality imbalance was not observed in the longer follow-up period (25 deaths with benazepril vs. 23 with placebo).
- A significant majority of patients in both groups received ACE inhibitors during the extension period.
Conclusions:
- Benazepril demonstrates a long-term beneficial effect in patients with chronic renal insufficiency.
- The non-randomized nature of the extension period requires careful interpretation of the intention-to-treat analysis results.
- Long-term ACE inhibitor use may be crucial for managing progressive renal insufficiency.
Abstract:
The Angiotensin-converting-enzyme Inhibition on Progressive Renal Insufficiency (AIPRI) Study showed that the ACE inhibitor benazepril provides protection against loss of renal function in patients with chronic renal insufficiency (CRI) caused by various renal diseases. As a result of unexpectedly low mortality in the placebo group, there was a substantial imbalance in mortality during the course of this study (8 patients on benazepril vs. 1 on placebo). The aim of the extension study was to follow-up the patients from the AIPRI core study until autumn 1996, focusing on CRI progression and mortality. Data collection was post hoc. Patients were treated according to investigators' usual practices, without knowledge of the core study trial medication or (initially) the core trial results. A new primary efficacy parameter was defined as the time from the start of core study treatment to the occurrence of the first event in the combined composite end-point of dialysis, renal transplantation or death related to renal disease. Serial serum creatinine levels and all-cause mortality were also recorded. The median total follow-up for core + extension periods was 6.6 years. Many patients from both treatment groups (64% on benazepril and 61% on placebo) received ACE inhibitors during follow-up. In the intention-to-treat analysis of the core + extension data, only 79 of 300 patients from the benazepril group, compared to 102 of the 283 patients from the placebo group needed dialysis or renal transplantation, or died related to renal disease (P < 0.013, log-rank test). The mortality imbalance seen in the core trial was not evident with the longer follow-up (25 deaths in the benazepril and 23 in the placebo group, before dialysis). These data clearly demonstrate a long-term beneficial effect in patients randomized to take benazepril during the core study, but because treatment during the extension period was not randomized, the results of this intention-to-treat analysis need to be interpreted with care.