Olmesartan delays the onset of microalbuminuria, but more deaths seen

The long awaited ROADMAP trial was recently published in the New England Journal of Medicine. This randomized controlled trial enrolled 4,447 patients to determine whether treatment with the angiotensin receptor blocker olmesartan could delay or prevent microalbuminuria.

In the study, blood pressure was targeted at less than 130/80 mmHg, yet patients randomized to the ARB group had a lower clinic blood-pressure by 3.1/1.9 overall. The time to onset of microalbuminuria was increased by 23% in the olmesartan group [hazard ratio for the onset of microalbuminuria 0.77; 95% confidence interval, 0.632 0.94; P=0.01]. However surprisingly, there was fewer cardiovascular deaths in the placebo group [3 versus 15, P=0.01].

Microalbuminuria is associated with excess cardiovascular risk particularly in patients with diabetes or other cardiovascular risk factors. Furthermore, elevation in urinary albumin, particularly in large quantities [> 1 g per day] has been associated with adverse renal outcomes. There has always been a corresponding temptation to lower or prevent proteinuria to prevent both renal and cardiovascular outcomes. The current study is a replication of the BENEDICT study, previously showing that randomization to an ACE inhibitor could prevent albuminuria. While the current study seems to reproduce these results, it also documented an access in cardiovascular mortality in the group despite improving their urinary protein parameters.

One explanation for the findings in this study could be that a reduction in blood pressure below the so-called J point could have contributed to an excess cardiovascular event rate, despite improvement in a marker known to be associated with cardiovascular risk. The study also then brings into question the utility of using microalbuminuria as a clinical endpoint that one should treat in order to reduce excess cardiovascular or renal risk. The present study certainly does not support this approach. However, further studies, possibly with longer follow-up would be required to answer the question more conclusively.