23.8
588 (13)
27.9
13%
2% to 23%
0.021
Components of Primary Composite Endpoint (as a first event)
Stroke (nonfatal)
209 (5)
286 (6)
Myocardial infarction (nonfatal)
174 (4)
168 (4)
Cardiovascular mortality
125 (3)
134 (3)
Secondary Endpoints (any time in study)
Stroke (fatal/nonfatal)
232 (5)
10.8
309 (7)
14.5
25%
11% to 37%
0.001
Myocardial infarction
(fatal/nonfatal)
198 (4)
9.2
188 (4)
8.7
-7%
-13% to 12%
0.491
Cardiovascular mortality
204 (4)
9.2
234 (5)
10.6
11%
-7% to 27%
0.206
Due to CHD
125 (3)
5.6
124 (3)
5.6
-3%
-32% to 20%
0.839
Due to Stroke
40 (1)
1.8
62 (1)
2.8
35%
4% to 67%
0.032
Other‡
39 (1)
1.8
48 (1)
2.2
16%
-28% to 45%
0.411
Although the LIFE study favored losartan potassium over atenolol with respect to the primary endpoint (p=0.021), this result is from a single study and, therefore, is less compelling than the difference between losartan potassium and placebo. Although not measured directly, the difference between losartan potassium and placebo is compelling because there is evidence that atenolol is itself effective (vs. placebo) in reducing cardiovascular events, including stroke, in hypertensive patients.
Other clinical endpoints of the LIFE study were: total mortality, hospitalization for heart failure or angina pectoris, coronary or peripheral revascularization procedures, and resuscitated cardiac arrest. There were no significant differences in the rates of these endpoints between the losartan potassium and atenolol groups.
For the primary endpoint and stroke, the effects of losartan potassium in patient subgroups defined by age, gender, race and presence or absence of isolated systolic hypertension (ISH), diabetes, and history of cardiovascular disease (CVD) are shown in Figure 3 below. Subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.
Figure 3: Primary Endpoint Events† within Demographic Subgroups
Symbols are proportional to sample size.
#Other includes Asian, Hispanic, Asiatic, Multi-race, Indian, Native American, European.
†Adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy.
14.3 Nephropathy in Type 2 Diabetic PatientsThe RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3.0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]).
Patients were randomized to receive losartan potassium 50 mg once daily or placebo on a background of conventional antihypertensive therapy excluding ACE inhibitors and angiotensin II antagonists. After one month, investigators were instructed to titrate study drug to 100 mg once daily |
