We are evaluating the literature for managing chronic kidney disease and would very much appreciate opinions regarding the following issue in analyzing the results of an RCT comparing enalapril with placebo in diabetics.

Ref:  Brenner BM, Cooper ME, de Zeeuw D, et al., for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345:861-9.

The patients were type 2 diabetes with nephropathy.  Baseline characteristics, including disease severity, were similar in the two groups. 

Outcomes were –

--the composite of a doubling of the baseline serum creatinine level, end-stage renal disease (ESRD), or death,

--and the composite of cardiovascular morbidity or mortality.

The authors used the Cox regression model and reported significant  RRRs for all of the endpoints except death.

The authors explain that there is often a difference between the risk reduction as determined on the basis of the Cox regression model and the risk reduction as determined on the basis of the crude rates of events. They state that the difference results in part from the fact that the Cox regression model accounts for the time at risk — i.e., the longer average follow-up in the losartan group than in the placebo group.

In this study the mean follow-up was 3.4 years and actual follow-up ranged from  2.3-4.6 years.  The authors presented the numbers of events per 100 patient-years of follow-up.

The data is shown below:

We recalculated the P value for the primary outcome, basing our calculations on crude event rates. We did not get statistically significant results (p=0.235).

We are not statisticians but believe that the crude event rates should also be statistically significant for the study to be valid.

We would be most grateful for opinions regarding this question and our belief that we should be able to use crude event rates for these outcomes.