Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial
Authors: Toyoda Kazunori , Koga Masatoshi , Tanaka Kenta , Uchiyama Shinichiro , Sunami Hisato , Omae Katsuhiro , Kimura Kazumi , Hoshino Haruhiko , Fukuda-Doi Mayumi , Miwa Kaori , Koge Junpei , Okada Yasushi , Sakai Nobuyuki , Minematsu Kazuo , Yamaguchi Takenori ,   for the CSPS.com Trial Investigators,   Study sponsor, Yamaguchi Takenori ,   Principal Investigator, Yamaguchi Takenori ,   Steering Committee, Toyoda Kazunori , Uchiyama Shinichiro , Hoshino Haruhiko , Kimura Kazumi , Okada Yasushi , Sakai Nobuyuki , Tanaka Kotaro ,   Protocol Authoring Committee, Toyoda Kazunori ,   Independent Data Monitoring Committee, Naritomi Hiroaki , Goto Shinya , Isomura Tatsuya ,   Event Evaluation Committee, Minematsu Kazuo , Houkin Kiyohiro , Matsumoto Masayasu , Terayama Yasuo , Tomimoto Hidekazu , Tominaga Teiji , Yasuda Satoshi ,   Statistical Analysis Committee, Orikasa Hideki , Kumagai Naoko ,   Publication Committee,   Clinical Sites and Site Investigators, by Enrolment, Miyasaki Akihiro , Isobe Masanori , Suda Yoshitaka , Kitagawa Kazuo , Nagatsuka Kazuyuki , Toru Shuta , Katsuno Makoto , Murao Kenichi , Ikeda Norio , Nakashima Kazuya , Okabe Shinichi , Kurimoto Masanori , Ihara Ikuo , Matsuoka Hideki , Mabuchi Shoji , Hara Hideo , Yoshimoto Teruyuki , Matsuoka Takeshi , Arai Yoshikazu , Iwasaki Yasuyuki , Hattori Manabu , Takahashi Kazuya , Fukushima Yoshihisa , Ezura Masayuki , Takeda Yasuaki , Nakahara Kimihiro , Okada Masahiro , Mitaki Shingo , Yoshida Kosuke , Kamiyama Kenji , Kuwashiro Takahiro , Iwanaga Takeshi , Takahashi Akira , Maruyama Junichi , Yamamoto Teiji , Maruyama Michiyuki , Taguchi Yoshiharu , Hashidume Kazuhiro , Takizawa Katsumi , Iguchi Yasuyuki , Kitajima Kazuhito , Yoshimura Shinichi , Arakawa Syuji , Inoue Takeshi , Yamaguchi Hiroyuki , Suzuki Susumu , Watanabe Youichi , Yasutomi Daisuke , Tanaka Ryota , Yamamoto Takuji , Ando Tetsuo , Ito Yasuhiro , Hattori Naoki , Yamamoto Nobutaka , Takahashi Tsutomu , Arihiro Syoji , Kanda Naoaki , Hamaguchi Hirotoshi , Kasuya Junji , Honda Masaru , Oyama Hiroshi , Yoshida Hidefumi , Okuda Satoshi , Matsuura Keita , Ieda Toshiaki , Kanzawa Takao , Takahashi Makio , Sadahiro Hirokazu , Miyahara Takahiro , Yamada Masahiko , Aoki Takeshi , Nakase Taizen , Hayashi Katsuhiko , Umemura Toshitaka , Tsugu Yasukuni , Miya Fumitaka , Otani Ryo , Yamada Keiichi , Kajimoto Yoshinaga , Nakane Hiroshi , Shinno Kiyohito , Hara Akio , Saito Ryoichi , Araki Yuzo , Otsuki Toshiho , Abe Koji , Kin Shigenari , Tsuji Takehisa , Sakai Shota , Tsuboi Yoshio , Kawamorita Atsushi , Shimizu Hiroaki , Araki Nobuo , Hata Takashi , Ryu Hiroshi , Yamatani Kazumasa , Minami Shinji , Maruta Takahiro , Eto Masaki , Takayama Katsutoshi , Hashikawa Kazuo , Mabuchi Eiichiro , Sakagami Yoshio , Tsuchimoto Syoji , Kitayama Jiro , Shirakawa Kiyoshi , Takahashi Haruki , Uchinokura Syunro , Osaka Naohiro , Imafuku Ichiro , Otsuka Toshiro , Itabashi Ryo , Kujiraoka Yuji , Miura Naohisa , Nomura Koichi , Kobari Masahiro , Yasui Keizo , Kashino Susumu , Murata Hiroto , Nozaki Kazuhiko , Yamashita Kosuke , Matsumoto Katsumi , Shibata Yuji , Aoyama Atsuo , Watanabe Yoshimasa , Eto Toru , Mekaru Susumu , Honda Tsuneo , Seike Masato , Kurisaka Masahiro , Imaizumi Toshio , Wada Kojiro , Suzuki Norihiro , Yoshino Atsuo , Hara Yukiko , Takizawa Shunya , Kamimoto Kaoru , Iizuka Hiroshi , Toma Yasuo , Komuro Taro , Sueyoshi Atsushi , Nakajima Yoshikazu , Sakaki Takayuki , Miyake Hiroji , Idei Masaru , Hitotsumatsu Tsutomu , Nakahara Shigehiro , Kawanishi Masahiko , Kitaoka Takuji , Isobe Naoyuki , Hokama Masanobu , Shibata Toshihide , Tsuruta Kazuhito , Moriki Akihito , Makino Masahiro , Otaki Masafumi , Ajiki Minoru , Yamazaki Takaaki , Houkin Kiyohiro , Yasui Nobuyuki , Hirata Koichi , Kato Hiroyuki , Suzuki Ichiro , Kawamata Takakazu , Uesaka Yoshikazu , Yamashita Kohei , Enomoto Yukiko , Onodera Osamu , Ikeda Masato , Miyamoto Susumu , Sakaguchi Manabu , Nakase Hiroyuki , Yagita Yoshiki , Kitahara Tetsuhiro , Irie Katsumi , Kusuhara Tomohiko , Kawazoe Kazumasa , Nagahiro Shinji , Kawada Norikazu , Adachi Akiko , Fukusako Toshihiro , Tsuruta Wataro , Fujimura Naoko , Koizumi Takayuki , Tomimitsu Hiroyuki , Fujimoto Shigeru , Tsuchiya Tsukasa , Aizawa Hitoshi , Ishizu Nobutaka , Nogawa Shigeru , Furumoto Hideharu , Ueda Toshihiro , Imae Syogo , Nakayama Teiji , Namba Hiroki , Ochiai Jun , Yamana Tomoko , Mase Mitsuhito , Matsukawa Noriyuki , Niwa Hisayoshi , Muramatsu Masatoshi , Nakashima Yoshio , Iwamoto Fuminori , Yoneda Syunichi , Hashimoto Kenji , Matsushita Tatsuo , Kunieda Takenobu , Masuo Osamu , Yamamoto Hirotaka , Hosomi Naohisa , Ogami Ryo , Kuramoto Koichi , Matsumoto Takahiro , Shinozaki Hirotsugu , Sugimori Hiroshi , Hashimoto Yoichiro , Suzuki Hidenori , Waza Masahiro , Kujyuro Yuki , Kamei Eiichi , Uchida Yasufumi , Nagayama Masao , Hiroki Masahiko , Sakura Hiroshi , Noujo Tatsuru , Tajima Yasutaka , Wada Hajime , Hodozuka Akira , Ide Wataru , Shibata Yasushi , Yamamoto Shinji , Ishihara Masayuki , Miyata Satsuki , Matsuoka Yoshiyuki , Sakurai Yasuhisa , Miura Yoshiharu , Yokota Takanori , Iwabuchi Satoshi , Tsuruta Wataro , Arimoto Hirohiko , Suda Sumio , Ohashi Takashi , Kuroda Katsuhiro , Matsuhisa Takashi , Yokoyama Kazutoshi , Katada Eiichi , Fujishiro Kenichiro , Inukai Akira , Kobayashi Yasushi , Sakai Hideki , Yamamoto Kenichi , Asakura Ken , Yoshimoto Yuhei , Kusano Yoshikazu , Takahashi Ryoichi , Higashi Sotaro , Park Cheho , Nakada Mitsutoshi , Matsui Makoto , Nagakane Yoshinari , Yoshioka Akira , Makino Masahiro , Yamaguchi Kazuyoshi , Hagihara Yasushi , Yamada Tomonori , Hashimoto Kenji , Fujita Toshiaki , Kumagai Tetsuya , Sumida Masayuki , Morioka Motohiro , Oboshi Hiroaki , Kitazono Takanari , Ando Yukio , Minato Seiichiro , Agawa Masahito , Kono Takeshi , Izumidani Tomohiko , Ueba Tetsuya , Takeuchi Hiroaki , Monden Syuji , Shiraishi Syoji , Syoji Hidehiko , Nakamura Tatsuya , Ikawa Naoki , Sugihara Hiroshi , Toyonaga Shinichi , Kon Hiroyuki , Kanamori Yuji , Tanaka Hiroaki 
Published: July 2024

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03–1.36), that of a 10 mmHg SBP increase was 1.14 (1.03–1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00–1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.