rdial infarction or cardiovascular death, analyzed using an intention-to-treat (ITT) approach. The table shows the number of events for each component in two different ways. The Components of Primary Endpoint (as a first event) counts only the events that define the primary endpoint, while the Secondary Endpoints count all first events of a particular type, whether or not they were preceded by a different type of event.
Table 2 Incidence of Primary Endpoint Events
COZAAR Atenolol Risk
Reduction* 95%
CI p-Value
*
Adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy
†
Rate per 1000 patient-years of follow-up
‡
First report of an event, in some cases the patient died subsequently to the event reported
§
Death due to heart failure, non-coronary vascular disease, pulmonary embolism, or a cardiovascular cause other than stroke or coronary heart disease
N (%) Rate† N (%) Rate†
Primary Composite Endpoint
508 (11)
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 COZAAR 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 COZAAR and placebo. Although not measured directly, the difference between COZAAR 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 COZAAR and atenolol groups.
For the primary endpoint and stroke, the effects of COZAAR 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
Race
In the LIFE study, Black patients treated with atenolol were at lower risk of experiencing the primary composite endpoint compared with Black patients treated with COZAAR. In the subgroup of Black patients (n=533; 6% of the LIFE study patients), there were 29 primary endpoints among 263 patients on atenolol (11%, 26 per 1000 patient-years) and 46 p
