Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke
Authors: Toyoda Kazunori , Yamagami Hiroshi , Kitagawa Kazuo , Kitazono Takanari , Nagao Takehiko , Minematsu Kazuo , Uchiyama Shinichiro , Tanahashi Norio , Matsumoto Masayasu , Nagata Izumi , Nishikawa Masakatsu , Nanto Shinsuke , Shirai Toshiaki , Abe Kenji , Ikeda Yasuo , Ogawa Akira , Ozaki Yukio , Go Yoshinori , Gi Hidefuku , Furui Eisuke , Kosaka Satoru , Uenohara Hiroshi , Fukuyama Kozo , Maruki Chikashi , Takenaka Katsunobu , Ogiichi Tsuneaki , Matsushima Kazushi , Osaki Masato , Nakagawa Hidemitsu , Aoki Michio , Sakai Nobuyuki , Kuroki Kazuhiko , Mori Takahisa , Uno Eiichi , Terasaki Tadashi , Metoki Norifumi , Naka Takashi , Ohnishi Hideyuki , Koyama Hideki , Ogihara Kotaro , Kiriyama Hideki , Oki Shuuichi , Murao Kei , Matsumoto Masahiro , Suzuki Kazunari , Saito Shinjiro , Suda Sumio , Sadatomo Takashi , Miyake Hiroji , Itamoto Kouji , Fujita Keishi , Ohashi Toshihiko , Ito Hiroki , Ito Yasuhiro , Dehara Makoto , Hitotsumatsu Tsutomu , Hirose Makoto , Nakagaki Yusuke , Takemura Sunao , Tomimitsu Hiroyuki , Izuta Makoto , Mekaru Susumu , Kin Shigenari , Akaike Yuji , Miyatake Masaki , Wada Naomichi , Shibata Norio , Koyama Kazuo , Ichikawa Yasumitsu , Torii Tsuyoshi , Nakane Hiroshi , Kobayashi Yasushi , Kida Shinya , Nishino Shigeki , Tabata Hitoshi , Sano Motoki , Fuｊigasaki Hiroto , Nagatsuka Kazuyuki , Koga Masatoshi , Fujita Hitoshi , Yasaka Masahiro , Nakahara Kimihiro , Tomiyama Masahiko , Fujita Tsuneo , Hoshi Seiichiro , Ota Takahiro , Orimo Satoshi , Momose Yoshio , Yamashita Katsuhiro , Shingaki Tatsuya , Kaku Yasuhiko , Terasawa Hideo , Kawamoto Yukihiko , Tokunaga Yoshiharu , Chiba Kei , Okada Yoshio , Yanai Yoshimi , Sato Atsushi , Miake Hirotomo , Imai Shu , Morimoto Masanori , Nunomura Mitsuru , Irie Shinsuke , Konno Shu , Kanzawa Takao , Hayase Makoto , Yoshino Kimihiro , Izumidani Tomohiko , Kanda Masutaro , Kurokawa Shinichiro , Kawada Sanami , Takase Keiichiro , Takashima Hiroshi , Haraguchi Koichi , Murai Hiroshi , Suzuki Mikio , Shimohata Mitsuteru , Takeuchi Shigekazu , Asakura Ken , Seguchi Tatsuya , Toba Yasuyuki , Nitta Eishun , Moriki Akihito , Koan Yoko , Kaneko Yoshiro , Suzuki Hisahiko , Yoshida Yasumasa , Naka Yutaka , Katayama Shinji , Imamura Eiji , Kazekawa Kiyoshi , Yu Iwae , Satoh Akira , Maruyama Junichi , Takahashi Akira , Arimoto Hirohiko , Hasegawa Yasuhiro , Fukazawa Seiji , Nishimura Yasuaki , Yamada Tomonori , Tsuji Tetsuro , Wakayama Akatsuki , Murao Kenichi , Tominaga Atsushi , Takaba Hitonori , Shimazaki Mitsunori , Ishibashi Yasuhiro , Oguni Eiichi , Kuroyanagi Takayuki , Tanno Hirokazu , Kawada Norikazu , Hondo Hideki , Matsuoka Hideki , Umemura Toshitaka , Hazama Takanori , Nishio Masami , Kawaba Tomoyuki , Wada Hirochiyo , Kamitsukasa Ikuo , Endo Sumio , Ueda Toshihiro , Narumi Osamu , Ino Tadashi , Yamada Takeshi , Ogiichi Tsuneaki , Urabe Takao , Ota Koichi , Kato Tokunori , Nomura Kyoichi , Ieda Toshiaki , Kagawa Masahiro , Mizota Takamitsu , Sueyoshi Kenji , Nakajima Yoshikazu , Fujita Toshiaki , Teramoto Yoshifumi , Mori Katsuharu , Takaya Satoru , Uemura Kazuya , Inukai Akira , Kubo Michiya , Takahashi Ryoichi , Takahashi Tsutomu , Kawauchi Masamitsu , Hirahara Kazuho , Matsumoto Sadayuki , Masuo Osamu , Nishi Shinsuke , Niwa Jun , Kubo Naohiko , Yamamoto Kanji , Watanabe Sadayoshi , Okuda Satoshi , Okamoto Kensho , Masago Atsuo , Ohuchi Masafumi , Harada Kunihiko , Hashimoto Yoichiro , Hayashi Kentaro , Fujita Nobuya , Mori Shuichi , Sakaguchi Manabu , Noda Kosumo , Aoki Takeshi , Nakase Taizen , Shibuya Satoshi , Kamei Satoshi , Kanbayashi Chisaku , Hattori Naoyuki , Takashima Shutaro , Manabe Yasuhiro , Kobayashi Nobuaki , Takano Katsunobu , Ajiki Minoru , Kondo Yoshiyuki , Hashikawa Kazuo , Ikezoe Koji , Morita Mitsuya , Kanbayashi Chisaku , Sakai Keiichi , Toi Sono , Iwamura Makoto , Takeuchi Juji , Suenaga Toshihiko , Takao Masaki , Kimura Takashi , Ozaki Akihiko , Kadekaru Tsutomu , Kato Tsutomu , Yamashita Kosuke , Ago Tetsuro , Tamaru Shinichi , Sekijima Yoshiki , Ito Hisashi , Yamasaki Masahiro , Kawai Hiromichi , Imai Keisuke , Sekine Tomoyuki , Inoya Hiroshi , Sawada Motoshi , Mano Kazuo , Sonoo Masahiro , Ikeda Masaki 
Published: February 2021

Background and Purpose:
High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied.

Methods:
This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP.

Results:
A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP.

Conclusions:
Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs.

Registration:

URL:
https://www.clinicaltrials.jp
; Unique identifier: JapicCTI-111582.