Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke: PRASTRO-I.

Affiliation

Collaborators: Ozaki Y, Go Y, Gi H, Furui E, Kosaka S, Uenohara H, Fukuyama K, Maruki C, Takenaka K, Ogiichi T, Matsushima K, Osaki M, Nakagawa H, Aoki M, Sakai N, Kuroki K, Mori T, Uno E, Terasaki T, Metoki N, Naka T, Ohnishi H, Koyama H, Ogihara K, Kiriyama H, Oki S, Murao K, Matsumoto M, Suzuki K, Saito S, Suda S, Sadatomo T, Miyake H, Itamoto K, Fujita K, Ohashi T, Ito H, Ito Y, Dehara M, Hitotsumatsu T, Hirose M, Nakagaki Y, Takemura S, Tomimitsu H, Izuta M, Mekaru S, Kin S, Akaike Y, Miyatake M, Wada N, Shibata N, Koyama K, Ichikawa Y, Torii T, Nakane H, Kobayashi Y, Kida S, Nishino S, Tabata H, Sano M, Fujigasaki H, Nagatsuka K, Koga M, Fujita H, Yasaka M, Nakahara K, Tomiyama M, Fujita T, Hoshi S, Ota T, Orimo S, Momose Y, Yamashita K, Shingaki T, Kaku Y, Terasawa H, Kawamoto Y, Tokunaga Y, Chiba K, Okada Y, Yanai Y, Sato A, Miake H, Imai S, Morimoto M, Nunomura M, Irie S, Konno S, Kanzawa T, Hayase M, Yoshino K, Izumidani T, Kanda M, Kurokawa S, Kawada S, Takase K, Takashima H, Haraguchi K, Murai H, Suzuki M, Shimohata M, Takeuchi S, Asakura K, Seguchi T, Toba Y, Nitta E, Moriki A, Koan Y, Kaneko Y, Suzuki H, Yoshida Y, Naka Y, Katayama S, Imamura E, Kazekawa K, Yu I, Satoh A, Maruyama J, Takahashi A, Arimoto H, Hasegawa Y, Fukazawa S, Nishimura Y, Yamada T, Tsuji T, Wakayama A, Murao K, Tominaga A, Takaba H, Shimazaki M, Ishibashi Y, Oguni E, Kuroyanagi T, Tanno H, Kawada N, Hondo H, Matsuoka H, Umemura T, Hazama T, Nishio M, Kawaba T, Wada H, Kamitsukasa I, Endo S, Ueda T, Narumi O, Ino T, Yamada T, Ogiichi T, Urabe T, Ota K, Kato T, Nomura K, Ieda T, Kagawa M, Mizota T, Sueyoshi K, Nakajima Y, Fujita T, Teramoto Y, Mori K, Takaya S, Uemura K, Inukai A, Kubo M, Takahashi R, Takahashi T, Kawauchi M, Hirahara K, Matsumoto S, Masuo O, Nishi S, Niwa J, Kubo N, Yamamoto K, Watanabe S, Okuda S, Okamoto K, Masago A, Ohuchi M, Harada K, Hashimoto Y, Hayashi K, Fujita N, Mori S, Sakaguchi M, Noda K, Aoki T, Nakase T, Shibuya S, Kamei S, Kanbayashi C, Hattori N, Takashima S, Manabe Y, Kobayashi N, Takano K, Ajiki M, Kondo Y, Hashikawa K, Ikezoe K, Morita M, Kanbayashi C, Sakai K, Toi S, Iwamura M, Takeuchi J, Suenaga T, Takao M, Kimura T, Ozaki A, Kadekaru T, Kato T, Yamashita K, Ago T, Tamaru S, Sekijima Y, Ito H, Yamasaki M, Kawai H, Imai K, Sekine T, Inoya H, Sawada M, Mano K, Sonoo M, Ikeda M.
Author information:
(1)Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
(K.T., K.M.).
(2)Department of Stroke Neurology, Osaka National Hospital, Japan
(H.Y.).
(3)Department of Neurology, Tokyo Women's Medical University School of Medicine, Japan
(K.K.).
(4)Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
(T.K.).
(5)Department of Neurology, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan
(T.N.).
(6)International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan
(S.U.).
(7)Department of Neurology, Saitama Medical University International Medical Center, Japan
(N.T.).
(8)Department of Neurology, Sakai City Medical Center, Osaka, Japan
(M.M.).
(9)Department of Neurosurgery, Kokura Memorial Hospital, Fukuoka, Japan
(I.N.).
(10)Clinical Research Support Center, Mie University Hospital, Japan
(M.N.).
(11)Nishinomiya Municipal Central Hospital, Hyogo, Japan
(S.N.).
(12)Clinical Development Department
(T.S.), R&D Division, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
(13)Biostatistics & Data Management Department
(K.A.), R&D Division, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
(14)Waseda University Faculty of Science and Engineering, Tokyo, Japan
(Y.I.).
(15)Department of Neurosurgery, Iwate Medical University, Japan
(A.O.).

Abstract

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.