Losartan and end-organ protection--lessons from the RENAAL study.
BACKGROUND
The Reduction in ENdpoints with the Angiotensin Antagonist Losartan (RENAAL) study reported that losartan delayed the progression of renal disease in patients with type 2 diabetes and nephropathy. Diabetic or renally impaired patients are at high cardiovascular risk, a risk potentially increased in patients with both conditions.


OBJECTIVE
This post hoc analysis examined whether baseline proteinuria was predictive of cardiovascular outcomes, and whether losartan modifies the risk of cardiovascular outcomes in these patients given its renal-protective effects.


METHODS
The RENAAL study compared losartan with placebo (in addition to conventional antihypertensive medications) in type 2 diabetic patients with proteinuria. Morbidity and mortality due to cardiovascular causes were ascertained, and the relationship between baseline proteinuria and cardiovascular outcome was determined. The effect of treatment with losartan was examined using three time-to-event analyses of composite cardiorenal outcomes as described below.


RESULTS
Increasing baseline proteinuria was associated with significantly increased risk of myocardial infarction (MI) and all-cause or cardiovascular death, but not stroke. Losartan significantly reduced the risk for the combined endpoint of end-stage renal disease (ESRD), MI, stroke, or death by 21% (p < or = 0.005), irrespective of whether all-cause or cardiovascular death was included in the analysis. In addition, losartan reduced the risk for the composite of ESRD or cardiovascular death by 19.2% (p < 0.05).


CONCLUSIONS
In patients with type 2 diabetes and nephropathy, there is an increased risk of MI and cardiovascular or all-cause mortality. Treatment with losartan is associated with a reduction in proteinuria, a delay in the onset of ESRD, and no increased risk of cardiovascular events in this pre-ESRD population.
Kowey
Peter R
PR
Main Line Health Heart Center, Wynnewood, Philadelphia, USA. koweypr@mlhheart.org
Dickson
Tania Z
TZ
Zhang
Zhongxin
Z
Shahinfar
Shahnaz
S
Brenner
Barry M
BM
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D019808:Losartan / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D011507:Proteinuria / Q000188:drug therapy; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan