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Special Issue: Current evidence and perspectives for hypertension management in Asia

Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis

Abstract

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7–134.1/76.9–78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0–127.4/73.5–74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.

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Acknowledgements

The authors appreciate the contribution of all the investigators and other clinical and research staff involved in the trial. The authors thank Hiroko Usami PhD, chief secretary of RESPECT study group, for her efforts in data management and protocol and manuscript preparation.

for the Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study Group

Chief Investigator Kazuyuki Shimada11, Writing Committee Kazuyuki Shimada12, Kazuo Kitagawa13, Yasumasa Yamamoto14, Hisatomi Arima15, Shinichiro Ueda16, Takahide Kohro17, Koji Yonemoto18, The Steering committee Kazuyuki Shimada19, Satoshi Umemura20, Yasushi Okada21, Genjiro Kimura22, Kazuaki Shimamoto23, Norio Tanahashi24, Jitsuo Higaki25, Masayasu Matsumoto26, The protocol committee Masayasu Matsumoto27, Sadayoshi Ito28, Shinichiro Ueda29, Yusuke Ohya30, Kazuo Kitagawa31, Yasumasa Yamamoto32, Hiromi Rakugi33, The endpoint committee Kazuo Minematsu34, Kazuomi Kario35, Yoshihiko Saito36, Yasuo Terayama37, Kazunori Toyoda38, Takafumi Okura39, Haruhiko Hoshino40, Hirofumi Makino41, Kazuo Eguchi42, Haruhito Uchida43, The Statistical analysis team Hisatomi Arima44, Takahide Khoro45, Koji Yonemoto46, The independent Data Monitoring Committee Shinichiro Uchiyama47, Hideki Etani48, Tatsuo Kohriyama49, Hidekazu Tomimoto50, Taku Yoshio51, Takao Saruta52, Shotai Kobayashi53, The data management center Hiroko Usami54, Hokkaido Satoshi Iihoshi55, Takeshi Mikami55, Nobuhiro Mikuni55, Kei Miyata55, Tomohiro Murakami55, Hideki Endo56, Takahito Fukui56, Kentaro Fumoto56, Keiji Hara56, Kaori Honjo56, Kenji Kamiyama56, Yusuke Kinoshita56, Masana Maeda56, Masaaki Mikamoto56, Daisuke Mori56, Takeo Murahashi56, Ryota Nomura56, Shusaku Noro56, Tatsuya Ogino56, Masahiro Okuma56, Yasuhumi Otake56, Koichiro Shindo56, Hironori Sugio56, Hidekazu Takada56, Kazuki Takahira56, Akiko Takeuchi56, Toshiichi Watanabe56, Yohei Yamaguchi56, Takeo Abumiya57, Kiyohiro Houkin57, Shigeki Matsumura58, Tomohiro Murakami58, Rikiya Shinohe59, Kiyomi Kuroshima60, Katsumi Takizawa60, Kazuto Yoshida60, Hideo Morimoto61, Naoyuki Hasebe62, Satoshi Koyama63, Junichi Maruyama63, Shinsuke Irie64, Aomori Prefecture Takahiro Nakano65, Yukari Ogasawara65, Hiroki Ohkuma65, Kazuo Shibanai66, Akita Prefecture Kentaro Hikichi67, Shinya Kobayashi67, Junta Moroi67, Taizen Nakase67, Takeshi Okada67, Daiki Takano67, Shunsuke Takenaka67, Shotaro Yoshioka67, Toshiharu Yanagisawa68, Yutaka Hirata69, Iwate Prefecture Shu Konno70, Tomohiko Sato71, Yamagata Prefecture Miiko Ito72, Rei Kondo72, Wataru Mori72, Shinjiro Saito72, Yasuaki Kokubo73, Miyagi Prefecture Hideaki Kato74, Hideki Oyama74, Kaneyuki Matsuo75, Masahiro Matsumoto76, Mari Nakamura76, Fukushima Prefecture Takayuki Koizumi77, Hiroyuki Sato77, Ibaraki Prefecture Yasushi Shibata78, Tochigi Prefecture Kazuo Eguchi79, Kazuomi Kario79, Masaaki Hashimoto80, Kazuo Eguchi80, Hideharu Kurita80, Eiji Matsumoto80, Gunma Prefecture Koji Ishiguro81, Ken Asakura82, Hiroya Fujimaki82, Kazuki Wakabayashi82, Kazunori Akaji83, Tomo Horikoshi83, Tadashige Kano83, Takao Kanzawa83, Takehiro Katano83, Hiroaki Kimura83, Ban Mihara83, Kentaro Suzuki83, Yohei Takayama83, Saitama Prefecture Akira Ishii84, Sin-ichi Momomura84, Hitoshi Sugawara84, Takeshi Yamashita84, Uichi Kaneko85, Toshie Takahashi85, Toshinari Arai86, Yoshihiro Tanaka87, Shigehisa Inokuma88, Yuji Kato89, Norio Tanahashi89, Chiba Prefecture Naoki Ishige90, kazuhiro Muramatsu91, Shigeru Nogawa91, Takahito Yoshizaki91, Takashi Ohashi92, Sumio Suda93, Tokyo, Yasuyuki Iguchi94, Hidetaka Mitsumura94, Tomohide Adachi95, Haruhiko Hoshino95, Fumie Konoeda95, Koichi Oki95, Ryota Tanaka96, Takao Urabe96, Kazuo Yamashiro96, Akihiro Ito97, Hirofumi Nakatomi97, Masaaki Shojima97, Kuniaki Otsuka98, Koichi Shibata98, Takato Abe99, Yoshiaki Itoh99, Koichi Oki99, Norihiro Suzuki99, Kazuo Kitagawa100, Sono Toi100, Tamio Teramoto101,Atsushi Fukunaga102, Yuki Kujuro102, Kouichi Ohta102, Takashi Osada102, Katuyoshi Shimizu102, Yasuhisa Kitagawa103, Kentaro Tokuoka103, Kanagawa Prefecture Masao Omura104, Hideyuki Kikyo105, Tomoya Kamide106, Yoshihisa Kitamura106, Katsuyoshi Miyashita106, Kentaro Mori106, Hiroshi Shima106, Akira Tamase106, Tsugio Akutsu107, Kazutoshi Nishiyama107, Shunya Takizawa108, Tsuyoshi Uesugi108, Nagano Prefecture Uichi Ikeda109, Megumi Koshikawa109, Saeko Yamasaki109, Atsushi Inoue110, Ishikawa Prefecture Yasuko Matsumoto111, Kazuyoshi Yamaguchi111, Genjirou Hirose112, Satoshi Kontani112, Kazuya Takasawa113, Niigata Prefecture Katsumi Hirahara114, Makoto Kodama115, Nobue Yagihara115, Shizuoka Prefecture Takashi Hata116, Makoto Hori116, Aichi Prefecture, Rokuhei Oda117, Ayuka Kubo118, Satoshi Okuda118, Kentaro Yamada119, Hiroki Takeuchi120, Yoshio Araki121, Mizuki Ito121, Joe Senda121, Toshihiko Wakabayashi121, Shinji Ito122, Tatsuro Mutoh122, Gifu Prefecture Yukinori Kawase123, Fumio Ando124, Mie Prefecture Shinya Okamoto125, Takuya Shimada126, Akihiro Shindo126, Masakatsu Nishikawa127, Atsushi Niwa127, Ryogen Sasaki127, Akihiro Shindo127, Hidekazu Tomimoto127, Hiroto Murata128, Kenichiro Yata129, Shiga Prefecture Koushun Matsuo130, Kyoto Hideo Yagi131, Toshiyuki Shiogai132, Yoshinari Nagakane133, Yasumasa Yamamoto133, Jun Fujinami134, Masanori Nakagawa134, Ryo Ohara134, Yasuhiro Tomii134, Yoshiki Arakawa135, Takeshi Funaki135, Masafumi Ihara135, Akihiro Kitamura135, Takakuni Maki135, Susumu Miyamoto135, Yoshifumi Nakaya135, Ryosuke Takahashi135, Yohei Takenobu135, Kazumichi Yoshida135, Tadashi Ino136, Nagako Murase137, Ryo Ohotani137, Yasuhiro Tomii138, Yasumasa Yamamoto138, Atsushi Kawashima139, Akiko Watanabe139, Yuko Hayashi140, Takuma Ohmichi140, Rei Yasuda140, Akira Yoshioka140, Natsuko Yuki140, Masahiro Makino141, Yasuhiro Tomii141, Tatsuyuki Yamaguchi141, Osaka, Jyo Matsuzaki142, Hitoshi Niki142, Shoichi Shiraishi142, Takehiko Yanagihara142, Keiichi Yamada143, Jun Hatate144, Kaori Miwa144, Shuhei Okazaki144, Shoji Arihiro145, Ryosuke Doijiri145, Kyoko Higashida145, Katsufumi Kajimoto145, Kotaro Miyashita145, Kazuyuki Nagatsuka145, Kozue Saito145, Yuri Sugiura145, Hotake Takizawa145, Takako Torii145, Kazunori Toyoda145, Chiaki Yokota145, Yoshinaga Kajimoto146, Toshihiko Kuroiwa146, Ryuzo Fukunaga147, Tsutomu Takahashi147, Kazutami Nakao148, Yuta Kajiyama149, Yasuyoshi Kimura149, Takashi Naka149, Hironori Otomune149, Takao Tanahashi149, Takuya Uehara149, Hiroyuki Hashimoto150, Toshihiko Uematsu150, Nara Prefecture, Kazuo Kataoka151, Satoshi Okayama152, Satoshi Somekawa152, Shuichi Yamada153, Rie Sasaki154, Shigeru Yamano154, Wakayama Prefecture Naoyuki Nakao155, Shinji Obayashi155, Hyogo Prefecture Hirotoshi Hamaguchi156, Tatsushi Toda156, Kazuo Washida156, Taku Hoshi157, Tomoyuki Kono157, Hiroaki Sekiya157, Norifumi Sugo157, Kenichi Todo157, Masaya Togo157, Hiroshi Yamagami157, Shiro Yamamoto157, Yoshihiko Shiro158, Norifumi Sugo158, Hirotoshi Hamaguchi159, Toshio Takaoka160, Shimane Prefecture Satoshi Abe161, Chizuko Hamada161, Masaki Ishihara161, Katuhiko Kadota161, Tomonori Nakagawa161, Hiroaki Oguro161, Hiroyuki Takayoshi161, Takuya Yamaguchi161, Shuuhei Yamaguchi161, Ryo Mizuhara162, Kazunori Okada162, Shingo Yamagata162, Kazunori Okada163, Akira Sasaki164, Okayama Prefecture Koji Abe165, Kentaro Deguchi165, Shoko Deguchi165, Yumiko Nakano165, Satoshi Hirai166, Masaaki Uno166, Kimihiko Yokosuka166, Yasuhiro Manabe167, Hiroshima Prefecture Hijiri Ito168, Shiro Aoki169, Naohisa Hosomi169, Yasuki Kihara169, Tomohiko Kisaka169, Hirofumi Maruyama169, Masayasu Matsumoto169, Hayato Araki170, Ryo Ogami170, Tsuyoshi Torii171, Noboru Yokoyama172, Takakazu Yokoyama172, Satoshi Kataoka173, Takeshi Kitamura173, Yamaguchi Prefecture Takashi Kanda174, Toshihiko Maeda174, Fumitaka Shimizu174, Kozaburo Seki175, Kagawa Prefecture Yuko Bando176, Masaki Ohara176, Kochi Prefecture Masahiro Yamasaki177, Noritaka Masahira178, Tetsuya Ueba178, Yusuke Ueba178, Ehime Prefecture Norio Sunami179, Yuichi Fujimoto180, Keiko Haro180, Hidenori Ogata180, Norihiko Shida180, Takeshi Matsumoto181, Kensho Okamoto181, Jitsuo Higaki182, Takafumi Okura182, Ryuichi Kawamoto183, Fukuoka Prefecture Shuji Arakawa184, Shoji Arihiro184, Hirofumi Shii185, Hidetoshi kanai185, Shigeru Fujimoto186, Juro Jinnouchi186, Takayuki Matsuki186, Masato Osaki186, Kimika Arakawa187, Ai Ibaraki187, Kanako Kiyohara187, Yuko Ohta187, Hideyuki Oniki187, Minako Sakaki187, Mitsuhiro Tominaga187, Takuya Tsuchihashi187, Saho Higashi188, Hiromi Ishikawa188, Koji Ishitsuka188, Jiro Kitayama188, Hiroshi Nakane188, Takeo Yoshimura189, Shunsuke Kakino190, Yoshirou Kaneko190, Kumamto Prefecture, Junnosuke Inoue191, Kagoshima Prefecture, Yoshikazu Maruyama192, Okinawa Prefecture, Katsunori Isa193, Yusuke Ohya193, Hirokuni Sakima193, Seigo Nakada194

Funding

The RESPECT study group was funded by Merck and Co. Inc., Bristol-Myers Squibb Company, Towa Pharmaceutical Co., Ltd., and Omron Corporation.

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Correspondence to Kazuo Kitagawa.

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KK reports grants and personal fees from Daiichi Sankyo, grants and personal fees from Bayer Inc., grants and personal fees from Takeda Pharmaceutical, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Kyowa Kirin, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Astellas Pharma, and grants and personal fees from Sanofi, outside the submitted work; HA reports research grants from Daiichi Sankyo, Takeda and Eisai, personal fees from Kyowa Kirin and nonfinancial research support from Phillips, outside the submitted work; YY has nothing to disclose; Ueda reports grants from Kowa, grants from Bayer, grants from Bristol Myers Squibb, personal fees from Tiho, personal fees from Kowa, personal fees from Dainippon Sumitomo, personal fees from Boehringer Ingelheim, grants from Pfizer, and grants from Daiichi Sankyo, outside the submitted work; HR reports grants and personal fees from MSD, during the conduct of the study, grants and personal fees from Daiichi Sankyo and Takeda Pharmaceutical, outside the submitted work, and grants from Astellas Pharma, Bayer Yakuhin, Dainippon Sumitomo Pharma, Kotobuki Pharmaceutical, Kyowa Kirin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Sanofi, and Teijin Pharma, outside the submitted work; TK has nothing to disclose; KY has nothing to disclose; MM reports personal fees from Kowa Pharmaceutical Co Ltd, personal fees from Takeda Pharmaceutical Co Ltd, personal fees from Bayer Yakuhin, Ltd, personal fees from Sanofi; KS has nothing to disclose; and TS reports personal fees from Dainippon-Sumitomo LTD, and Daiichi-Sankyo.

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Members of the Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study Group are listed below Acknowledgements.

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Kitagawa, K., Arima, H., Yamamoto, Y. et al. Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis. Hypertens Res 45, 591–601 (2022). https://doi.org/10.1038/s41440-022-00862-y

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