IN RESPONSE:
Dr. Good raises the concern that deaths in our study may have been higher in the group with the lower target blood pressure. It is important to note, however, that the deaths to which Dr. Good refers include only those that occurred before development of kidney failure (see the legend to our Figure 2). Consideration of deaths that occurred only before kidney failure may result in an informative censoring bias. That is, those patients who reach kidney failure first may be more likely to die; however, the deaths that occur after kidney failure are not included in the comparison. Our Figure 2 also does not provide data on follow-up time, which limits the comparison. In fact, median follow-up time was longer in the lower blood pressure group because of a delay in reaching kidney failure. A longer follow-up time will of course allow more deaths to occur.
Without censoring for kidney failure, there were 101 and 107 deaths in the low and usual blood pressure groups, respectively. When Cox regression analyses were used, the adjusted hazard ratio for mortality was 0.97 (P > 0.2) for the low target blood pressure group compared with the usual blood pressure group. Thus, there is no evidence to support the contention that the low blood pressure target results in a higher death rate.
Of note, we presented the results of the composite of kidney failure and mortality. This incorporates the competing risk for death into the kidney failure models. The results were consistent with the kidney failure models and demonstrated a benefit of the lower blood pressure target.
We agree with Dr. Kida that we cannot disprove the possibility that ACE inhibitor use may have had an effect on the outcome. As noted, however, we believe this is unlikely for the following reasons. First, adjustment for ACE inhibitor use did not diminish the benefit of the lower blood pressure target. Second, the benefit achieved in the low blood pressure target group (a hazard ratio of 0.68 with only a 19% difference in use of ACE inhibitors) is much greater than would be expected if one compared these results with those of other nondiabetic ACE inhibitor trials that observed a similar hazard ratio with a 100% difference in use of ACE inhibitors (1).
We believe that the MDRD Study differs from the studies mentioned by Dr. Kida because it involves longer follow-up and more kidney failure outcomes. We propose that it may take time for the benefit of a lower blood pressure goal to be appreciated.
1. Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135:73-87. [PMID: 11453706].