• Controlling Blood Pressure to Prevent a Second Stroke

    Trial, meta-analysis point to similar conclusions

    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 -- SPS3PAST-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.

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