Intensive blood pressure (BP) control to less than 130/80
mm Hg for secondary stroke prevention was supported in the prospective,
open
RESPECT trial and a meta-analysis, researchers reported.
The trial was stopped early and produced non-significant results, but
combining its data with that of three other trials showed that
intensive blood pressure treatment significantly reduced stroke
recurrence by 22% over standard treatment, wrote Kazuo Kitagawa, MD,
PhD, of Tokyo Women's Medical Center, and colleagues in
JAMA Neurology. Individually, none of the other three trials reported significant findings.
"The results of the RESPECT study, together with updated
meta-analysis, clearly showed the benefit of intensive blood pressure
lowering to less than 130/80 mm Hg compared with standard BP lowering to
less than 140/90 mm Hg," Kitagawa told
MedPage Today. "We hope
this finding is picked up in
future clinical guidelines about stroke
and hypertension and contributes to better blood pressure management for
secondary stroke prevention."
Blood
pressure targets below 140/90 mm Hg remain controversial for high-risk
patients, including people who have had a stroke, observed Craig
Anderson, MD, PhD, of the University of New South Wales, Australia, in
an accompanying
editorial.
"Although
SPRINT
provides some reassurance that the benefits of more intensive BP
lowering outweigh the justifiable concerns over harms such as
hypotension and renal impairment, especially in elderly individuals, the
study has been criticized about the generalizability of the results to
patients with a history of stroke, who were purposefully excluded, and
about the use of unattended automated
BP measurements to titrate therapy in a highly intensive monitoring schedule," Anderson wrote.
"The article by Kitagawa, et al. is an important addition to this
evidence base, not only in providing further support for the benefits of
more intensive BP lowering for secondary stroke prevention but also in
defining some of the complexities to achieving this goal in both
research and practice," he added.
In RESPECT, researchers recruited participants from 140 Japanese
hospitals from October 2010 until December 2016, when research funds ran
out. The goal was to recruit 5,000 participants, but only 1,263 people
were included in the intention-to-treat analysis.
Patients
were an average age of 67 and most (69%) were men; all had recovered
well from an acute stroke that had occurred within the previous 3 years.
They were randomized 1:1 to one of two targets -- blood pressure less
than 140/90 mm Hg (standard treatment), or blood pressure less than
120/80 mm Hg (intensive treatment) -- with stepwise, multidrug therapy
and were followed for an average of 3.9 years. The median time from
qualifying stroke to randomization was 4.6 months.
The primary endpoint was recurrent stroke. At baseline, average blood pressure was 145.4/83.6 mm Hg for all participants.
Target blood pressure levels were achieved by 61.7% in the standard
group and 32% in the intensive group. Throughout the overall follow-up,
average blood pressure was 133.2/77.7 mm Hg in the standard group and
126.7/74.4 mm Hg in the intensive group.
During follow-up, 91 recurrent strokes occurred: 87% were ischemic
and 13% hemorrhagic. The annualized rate of recurrence was 1.65% in the
intensive group and 2.26% in the standard group (HR 0.73, 95% CI
0.49-1.11,
P=0.15). Serious adverse events were similar in both groups.
When these results were pooled with data from three earlier studies
of blood pressure control for secondary stroke prevention --
SPS3,
PAST-BP, and
PODCAST
-- in a meta-analysis, intensive blood pressure lowering to a target
less than 130/80 mm Hg showed a reduced risk of recurrent stroke (RR
0.78, 95% CI, 0.64-0.96,
P=0.02). The absolute risk difference
was -1.5% (96% CI -2.6% to -0.4%) and the number needed to treat to
prevent one recurrent stroke was 67.
Like
many target-driven BP-lowering trials, RESPECT "faced particular
challenges from potentially eligible patients receiving better treatment
than would likely have occurred in routine practice, which affected
recruitment and event rates," Anderson observed. While the trial
protocol allowed people with systolic blood pressure ranging from 130 to
180 mm Hg to participate, most had good control "to achieve a systolic
baseline BP near 140 mm Hg," he noted.
"Another challenge was in achieving and maintaining BP separation
between the randomized groups," Anderson added. "Most trials have not
been able to achieve targets, and control patients have received more
intensive treatment than is usual in practice, resulting in smaller
between-group BP differences than planned."
Study limitations included the fact that RESPECT was underpowered,
and its treatment assignment was unmasked, which may have introduced
bias, noted Kitagawa and colleagues. People over age 85 were excluded
from the trial due to Japanese guidelines during the enrollment period.
In addition, "none of the individual studies had significant results for
secondary stroke prevention, although the meta-analysis showed clear
benefit," they wrote.
Last Updated July 29, 2019
The RESPECT study was funded by Merck, Bristol-Myers Squibb, Towa Pharmaceutical, and Omron.
Kitagawa
disclosed support from, and relevant relationships with, Daiichi
Sankyo, Bayer, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Kyowa
Hakko Kirin, Sumitomo Dainippon Pharma, Astellas Pharma, and Sanofi.
Co-authors disclosed multiple relevant relationships with industry.
Anderson
disclosed support from the National Health and Medical Research Council
of Australia and Takeda China (institutional), and relevant
relationships with Boehringer Ingelheim, Amgen, and Takeda.
Primary Source
JAMA Neurology
Secondary Source
JAMA Neurology
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