BACKGROUND AND
PURPOSE:
The
HOPE-3 trial (
Heart Outcomes Prevention Evaluation3) found that
antihypertensive therapy combined with a
statin reduced first
stroke among people at intermediate
cardiovascular risk. We
report secondary analyses of
stroke outcomes by
stroke subtype, predictors,
treatment effects in key subgroups.
METHODS:
Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular
risk factors but without overt
cardiovascular disease were randomized to candesartan 16 mg plus
hydrochlorothiazide 12.5 mg daily or placebo and to
rosuvastatin 10 mg daily or placebo. The effect of the interventions on
stroke subtypes was assessed.
RESULTS:
Participants were 66 years old and 46% were
women. Baseline
blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (
low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active
treatment. During 5.6 years of follow-up, 169
strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined).
Blood pressure lowering did not significantly reduce
stroke (
hazard ratio [HR], 0.80 [95% CI, 0.591.08]),
ischemic stroke (HR, 0.80 [95% CI, 0.551.15]),
hemorrhagic stroke (HR, 0.71 [95% CI, 0.341.48]), or
strokes of undetermined origin (HR, 0.92 [95% CI, 0.412.08]).
Rosuvastatin significantly reduced
strokes (HR, 0.70 [95% CI, 0.520.95]), with reductions mainly in
ischemic stroke (HR, 0.53 [95% CI, 0.370.78]) but did not significantly
affect hemorrhagic (HR, 1.22 [95% CI, 0.592.54]) or
strokes of undetermined origin (HR, 1.29 [95% CI, 0.572.95]). The combination of both interventions compared with double placebo substantially and significantly reduced
strokes (HR, 0.56 [95% CI, 0.360.87]) and
ischemic strokes (HR, 0.41 [95% CI, 0.230.72]).
CONCLUSIONS:
Among people at intermediate
cardiovascular risk but without overt
cardiovascular disease,
rosuvastatin 10 mg daily significantly reduced first
stroke.
Blood pressure lowering combined with
rosuvastatin reduced
ischemic stroke by 59%. Both
therapies are safe and generally well tolerated.