BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among
high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher,
but its role in persons at intermediate risk and with lower blood pressure is unclear.
METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705
participants at intermediate risk who did not have cardiovascular disease to receive
either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of
12.5 mg per day or placebo. The first coprimary outcome was the composite of death
from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the
second coprimary outcome additionally included resuscitated cardiac arrest, heart
failure, and revascularization. The median follow-up was 5.6 years. RESULTS: The mean
blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease
in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in
the placebo group. The first coprimary outcome occurred in 260 participants (4.1%)
in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio,
0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome
occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard
ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based
subgroups, participants in the subgroup for the upper third of systolic blood pressure
(>143.5 mm Hg) who were in the active-treatment group had significantly lower rates
of the first and second coprimary outcomes than those in the placebo group; effects
were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for
trend in the two outcomes). CONCLUSIONS: Therapy with candesartan at a dose of 16
mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated
with a lower rate of major cardiovascular events than placebo among persons at intermediate
risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of
Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
