MD Conference Express AHA 2013 - (Page 28)
CLINICAL TRIAL HIGHLIGHTS
Figure 3. Figure 1Safety Results
Key
22. Nutrition
Edoxaban 60 mg QD*
vs warfarin
Edoxaban 30 mg QD*
vs warfarin
Warfarin TTR 68.4%
ISTH Major Bleeding
HR (95% CI)
0.80
0.47
p Value
vs Warfarin
p<0.001
p<0.001
0.55
Fatal Bleeding
p=0.006
p<0.001
0.35
0.47
Intracranial
Hemorrhage
p<0.001
p<0.001
0.30
1.23
Gastrointestinal Bleeding
0.25
0.67
0.5
Edoxaban Superior
1.0
p=0.03
p<0.001
2.0
Edoxaban Inferior
*Dose reduced by 50% in selected patients.
*Dose reduced by 50% in selected patients. Both dose regimens of edoxaban
substantially reduced major, fatal, and intracranial bleeding. Gastrointestinal
bleeding
was
increased
with
high-dose
edoxaban
compared
with
warfarin, but reduced with the low-dose regimen compared with warfarin.
TTR=time in therapeutic range.
Reproduced with permission from RP Giugliano, MD.
Both edoxaban regimens were well tolerated and no
significant differences were observed in serious adverse
events or liver abnormalities compared with warfarin. In
terms of net clinical outcomes, both the high-dose and lowdose edoxaban regimens led to significant reductions in
composite endpoints of stroke/SEE/death/major bleeding
(p=0.003 and p<0.001, respectively), disabling stroke/
life-threatening bleeding/death (p=0.008 and p<0.001,
respectively), and stroke/SEE/life-threatening bleeding/
death (p=0.003 and p=0.007, respectively).
In this large, randomized, controlled international trial,
once-daily edoxaban was noninferior to well-managed
warfarin for the prevention of stroke and SEE, with a
trend toward fewer stroke/SEEs observed with the higher
dose. Both edoxaban regimens had superior net clinical
outcomes, which assessed various combinations of death,
stroke, and bleeding events, compared with warfarin.
Immediate Targeted Blood Pressure
Reduction Does Not Improve
Outcomes in Acute Stroke
Written by Nicola Parry
Jiang He, MD, PhD, Tulane University School of Public
Health and Tropical Medicine, New Orleans, Louisiana,
USA, presented the final results from the China
Antihypertensive Trial in Acute Ischemic Stroke [CATIS;
He J et al. JAMA 2013] trial, demonstrating that in acute
ischemic stroke patients with elevated blood pressure (BP),
antihypertensive treatment to reach a lower target BP does
not reduce their risk for death or disability within 14 days.
28
December 2013
CATIS was a multicenter, randomized trial, designed
to evaluate whether immediate BP reduction to a BP target,
within 48 hours of symptom onset, in patients with acute
ischemic stroke would reduce morbidity and mortality
compared with allowing hypertension during the
acute hospitalization.
Inclusion criteria included age ≥22 years,
ischemic stroke onset within 48 hours confirmed
by imaging (computed tomography or magnetic
resonance imaging), systolic BP (SBP) ≥140
and <220 mm Hg and diastolic BP (DBP)
≥80 mm Hg, and no contraindications to antihypertensive
therapy Patients with severe heart failure, acute
coronary syndrome, aortic dissection, atrial fibrillation,
cerebrovascular stenosis, resistant hypertension, and
those in a deep coma were excluded, as were individuals
receiving intravenous thrombolytic therapy.
The primary endpoint of the study was a combination
of death and major disability within 14 days, or at the
time of discharge, if that occurred prior to 14 days.
The secondary outcome was a composite of all-cause
mortality and major disability (a score of 3 to 5 on the
modified Rankin Scale) over 3 months of follow-up.
A total of 4071 patients were randomized to either
antihypertensive treatment to reduce SBP by 10% to
25% within the first 24 hours after randomization and
then to a target BP <140/90 mm Hg within 7 days to
be maintained during the hospitalization (n=2038) or
no antihypertensive treatment during hospitalization
(n=2033). At baseline, the mean age of study participants
was 62.0 years, and 64.0% were men. Stroke severity
was similar in both groups, as assessed using the
National Institutes of Health Stroke Scale (median score
4.0). The mean time from onset of ischemic stroke to
randomization was 15.3 and 14.9 hours in the treatment
and control groups, respectively; mean systolic BP at
entry was 166.7 and 165.6 mm Hg, and mean diastolic BP
was 96.8 and 96.5 mm Hg.
Various antihypertensive agents were used in the
treatment group, including intravenous angiotensinconverting enzyme inhibitors (enalapril, first-line),
calcium channel blockers (second-line), and diuretics
(third-line).
Within 24 hours, mean SBP decreased by an average of
12.7% in the treatment group, and 7.2% in the control group
(difference, −5.5%; 95% CI, −4.9 to −6.1; p<0.001). And by
Day 7, mean SBP was 137.3 mm Hg in the treatment group,
and 146.5 mm Hg in the control group (difference, −9.3 mm
Hg; 95% CI, −10.1 to −8.4; p<0.001). However, at 14 days
or hospital discharge, there was no significant difference
in primary outcome between the treatment and control
groups (683 vs 681 events; OR, 1.00; 95% CI, 0.88 to 1.14;
p=0.98; Table 1).
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