if the trough blood pressure goal (140/90 mmHg) was not achieved. Overall, 72% of patients received the 100-mg daily dose more than 50% of the time they were on study drug. Because the study was designed to achieve equal blood pressure control in both groups, other antihypertensive agents (diuretics, calcium-channel blockers, alpha- or beta-blockers, and centrally acting agents) could be added as needed in both groups. Patients were followed for a mean duration of 3.4 years.
The study population was diverse with regard to race (Asian 16.7%, Black 15.2%, Hispanic 18.3%, White 48.6%). Overall, 63.2% of the patients were men, and 66.4% were under the age of 65 years. Almost all of the patients (96.6%) had a history of hypertension, and the patients entered the trial with a mean serum creatinine of 1.9 mg/dL and mean proteinuria (urinary albumin/creatinine) of 1808 mg/g at baseline.
The primary endpoint of the study was the time to first occurrence of any one of the following events: doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death. Treatment with losartan potassium resulted in a 16% risk reduction in this endpoint (see Figure 4 and Table 4). Treatment with losartan potassium also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality (see Table 4).
The mean baseline blood pressures were 152/82 mmHg for losartan potassium plus conventional antihypertensive therapy and 153/82 mmHg for placebo plus conventional antihypertensive therapy. At the end of the study, the mean blood pressures were 143/76 mmHg for the group treated with losartan potassium and 146/77 mmHg for the group treated with placebo.
Figure 4: Kaplan-Meier curve for the primary composite endpoint of doubling of serum creatinine, end stage renal disease (need for dialysis or transplantation) or death.
Table 4Incidence of Primary Endpoint Events
Incidence
Risk Reduction
95% C.I.
p-Value
Losartan
Placebo
Primary Composite Endpoint
43.5%
47.1%
16.1%
2.3% to 27.9%
0.022
Doubling of Serum Creatinine, ESRD and Death Occurring as a First Event
Doubling of Serum Creatinine
21.6%
26.0%
ESRD
8.5%
8.5%
Death
13.4%
12.6%
Overall Incidence of Doubling of Serum Creatinine, ESRD and Death
Doubling of Serum Creatinine
21.6%
26.0%
25.3%
7.8% to 39.4%
0.006
ESRD
19.6%
25.5%
28.6%
11.5% to 42.4%
0.002
Death
21.0%
20.3%
-1.7%
-26.9% to 18.6%
0.884
The secondary endpoints of the study were change in proteinuria, change in the rate of progression of renal disease, and the composite of morbidity and mortality from cardiovascular causes (hospitalization for heart failure, myocardial infarction, revascularization, stroke, hospitalization for unstable angina, or cardiovascular death). Compared with placebo, losartan potassium significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine |
