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, COZAAR 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 concentration. There was no significant difference in the incidence of the composite endpoint of cardiovascular morbidity and mortality.

The favorable effects of COZAAR were seen in patients also taking other anti-hypertensive medications (angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors were not allowed), oral hypoglycemic agents and lipid-lowering agents.

For the primary endpoint and ESRD, the effects of COZAAR in patient subgroups defined by age, gender and race are shown in Table 4 below. Subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.

Table 4 Efficacy Outcomes within Demographic Subgroups 
 
 Primary Composite Endpoint ESRD

 No. of Patients COZAAR
Event Rate
% Placebo
Event Rate
% Hazard Ratio
(95% CI) COZAAR
Event Rate
% Placebo
Event Rate
% Hazard Ratio
(95% CI)
Overall Results 1513 43.5 47.1 0.839 (0.721, 0.977) 19.6 25.5 0.714 (0.576, 0.885)
Age
 
<65 years 1005 44.1 49.0 0.784 (0.653, 0.941) 21.1 28.5 0.670 (0.521, 0.863)
≥65 years 508 42.3 43.5 0.978 (0.749, 1.277) 16.5 19.6 0.847 (0.560, 1.281)
Gender
 
Female 557 47.8 54.1 0.762 (0.603, 0.962) 22.8 32.8 0.601 (0.436, 0.828)
Male 956 40.9 43.3 0.892 (0.733, 1.085) 17.5 21.5 0.809 (0.605, 1.081)
Race

Asian 252 41.9 54.8 0.655 (0.453, 0.947) 18.8 27.4 0.625 (0.367, 1.066)
Black 230 40.0 39.0 0.983 (0.647, 1.495) 17.6 21.0 0.831 (0.456, 1.516)
Hispanic 277 55.0 54.0 1.003 (0.728, 1.380) 30.0 28.5 1.024 (0.661, 1.586)
White 735 40.5 43.2 0.809 (0.645, 1.013) 16.2 23.9 0.596 (0.427, 0.831)

INDICATIONS AND USAGE

Hypertension
COZAAR is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, including diuretics.

Hypertensive Patients with Left Ventricular Hypertrophy
COZAAR is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients. (See PRECAUTIONS, Race and CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke, Race.)

Nephropathy in Type 2 Diabetic Patients
COZAAR is indicated for the treatment of diabetic