Low-dose aspirin therapy in patients with type 2 diabetes and reduced glomerular filtration rate: subanalysis from the JPAD trial

Yoshihiko Saito, Takeshi Morimoto, Hisao Ogawa, Masafumi Nakayama, Shiro Uemura, Naofumi Doi, Hideaki Jinnouchi, Masako Waki, Hirofumi Soejima, Seigo Sugiyama, Sadanori Okada, Yasuhiro Akai, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes Trial Investigators, Hisao Ogawa, Yoshihiko Saito, Masafumi Nakayama, Masao Kanauchi, Shiro Uemura, Takeshi Morimoto, Izuru Masuda, Masafumi Nakayama, Masao Kanauchi, Hirotsugu Ueshima, Hiroo Imura, Kazuo Kimura, Takeshi Morimoto, Makiko Ohtorii, Eri Miyake, Ai Mizutani, Kimiko Sakamoto, Hideaki Jinnouchi, Yoichi Hanaoka, Masako Waki, Kyousuke Kawamura, Michio Shimabukuro, Kimiaki Nishiura, Takahiro Kawano, Yusuke Kyoda, Jun Hashiguchi, Tadashi Kagoshima, Masakazu Hanatani, Norihiko Matsumura, Naofumi Doi, Kenji Nakai, Yoshiyuki Kobayashi, Megumi Suzuki, Tsuneari Soeda, Yoshinobu Morikawa, Masashi Horimoto, Atsushi Hasegawa, Shigeru Yamano, Syuichi Matsuo, Yasuhiro Sakamoto, Izuru Masuda, Akiko Yasuno, Yuriko Fujinaga, Kazuko Horii, Takeshi Koga, Hiroshi Ogawa, Ken Ozaki, Makoto Ikemura, Motomu Hayashi, Ikuo Yabuta, Kiyotaka Sughihara, Akihiro Yazaki, Joji Masuda, Yoshiharu Nishitani, Masaki Naito, Shigenobu Ote, Kazuhiko Yamada, Chikashi Wakabayashi, Yoshiaki Fukuoka, Keiji Mahara, Hirofumi Kan, Eiji Oshima, Toshio Sutani, Koichi Hoda, Koryo Sawai, Kenichi Yamaga, Tomoki Nakamura, Shinya Okamoto, Hiroaki Horie, Kenichi Ashihara, Hiroshi Miki, Hisaharu Makino, Takafumi Odo, Yoshihisa Iseri, Hiroyuki Tanaka, Kousuke Marutsuka, Akira Nakatani, Hironori Murakami, Yoshiko Shioya, Yutaka Horio, Tsuneo Ikeda, Kazuo Machii, Masanori Kamura, Keiichiro Ban, Yoshihiro Fujii, Kazuo Nishimoto, Susumu Misugi, Tetsuo Munakata, Katsutoshi Yoshimura, Shigetoshi Minami, Takao Nakashima, Hirofumi Ogata, Atuko Hifumi, Nobuko Sakurai, Ryuichiro Tsurusaki, Yoshito Yamanaka, Hiromitsu Yokota, Seishi Ichihara, Motoki Yoshinari, Yoko Sawada, Eiji Kawashima, Kazuo Goto, Yoshimi Kinoshita, Masao Kikukawa, Hiroharu Yamada, Yuya Tanaka, Mayumi Kiyota, Yoshihiro Kimura, Yasuhiro Morikami, Masahiro Fukuda, Takeshi Takami, Fumihiko Nakatani, Shojiro Naomi, Toshiaki Nasu, Tomohiro Sawada, Fuyuki Minagawa, Osamu Haraguchi, Norifumi Kondo, Hiroyuki Shono, Hiromichi Sugiyama, Takeshi Matsuo, Minoru Takaoka, Tamio Nakajima, Masamitsu Toihata, Kozaburo Matsuyama, Kenichi Komori, Toshio Tsubokura, Madoka Taguchi, Yuko Hiramori, Hiroto Okubo, Akihiro Iemura, Osamu Doi, Masayuki Ogihara, Kenji Misumi, Koji Seo, Ken Iwai, Masatoshi Naito, Seiji Ozawa, Kotaro Minoda, Hiromi Fujii, Kimiaki Miwa, Genshi Egusa, Isao Yasuda, Michiaki Ueda, Junichi Miyata, Midori Yoshimura, Masakuni Uemyama, Katumi Watanabe, Yoshikuni Haraguchi, Satoshi Tanazawa, Yoshiaki Osamura, Junji Shibata, Takashi Ono, Syuichi Kamijikkoku, Kazumi Yoshimoto, Etsuo Kinuwaki, Kazuo Kozuma, Kenji Onoue, Yukitaka Nakano, Nanami Abe, Haruo Araki, Kyoji Takaoka, Chieko Imamoto, Hisakazu Suefuji, Keisuke Sugimoto, Terufumi Matsunaga, Akiko Oya, Yoko Onishi, Keizo Kajiwara, Tetsuo Ikuno, Michiaki Doi, Toshiro Igaki, Hiroshi Bando, Tateo Ogura, Kenichi Doijiri, Taisuke Iwaoka, Kazunobu Akahoshi, Kenji Obata, Hisashi Shimono, Kaoru Tsuda, Shinya Yumoto, Keishiro Oka, Hironori Hasegawa, Hisao Fujimoto, Toshiya Atsumi, Akira Matsutani, Yohiyuki Katsuyama, Ryo Fukami, Yoshihisa Iseri, Yutaka Ishibashi, Kiyotaka Kudou, Tetsuo Kuwahara, Kazutaka Maeda, Akira Maki, Naiki Manda, Hirofumi Yasue, Yuji Mizuno, Sueo Momosaki, Koji Tokube, Fumishi Tomita, Tatsuaki Tsuchiya, Matahiro Yabuta, Hidei Yamada, Yoshihiko Saito, Takeshi Morimoto, Hisao Ogawa, Masafumi Nakayama, Shiro Uemura, Naofumi Doi, Hideaki Jinnouchi, Masako Waki, Hirofumi Soejima, Seigo Sugiyama, Sadanori Okada, Yasuhiro Akai, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes Trial Investigators, Hisao Ogawa, Yoshihiko Saito, Masafumi Nakayama, Masao Kanauchi, Shiro Uemura, Takeshi Morimoto, Izuru Masuda, Masafumi Nakayama, Masao Kanauchi, Hirotsugu Ueshima, Hiroo Imura, Kazuo Kimura, Takeshi Morimoto, Makiko Ohtorii, Eri Miyake, Ai Mizutani, Kimiko Sakamoto, Hideaki Jinnouchi, Yoichi Hanaoka, Masako Waki, Kyousuke Kawamura, Michio Shimabukuro, Kimiaki Nishiura, Takahiro Kawano, Yusuke Kyoda, Jun Hashiguchi, Tadashi Kagoshima, Masakazu Hanatani, Norihiko Matsumura, Naofumi Doi, Kenji Nakai, Yoshiyuki Kobayashi, Megumi Suzuki, Tsuneari Soeda, Yoshinobu Morikawa, Masashi Horimoto, Atsushi Hasegawa, Shigeru Yamano, Syuichi Matsuo, Yasuhiro Sakamoto, Izuru Masuda, Akiko Yasuno, Yuriko Fujinaga, Kazuko Horii, Takeshi Koga, Hiroshi Ogawa, Ken Ozaki, Makoto Ikemura, Motomu Hayashi, Ikuo Yabuta, Kiyotaka Sughihara, Akihiro Yazaki, Joji Masuda, Yoshiharu Nishitani, Masaki Naito, Shigenobu Ote, Kazuhiko Yamada, Chikashi Wakabayashi, Yoshiaki Fukuoka, Keiji Mahara, Hirofumi Kan, Eiji Oshima, Toshio Sutani, Koichi Hoda, Koryo Sawai, Kenichi Yamaga, Tomoki Nakamura, Shinya Okamoto, Hiroaki Horie, Kenichi Ashihara, Hiroshi Miki, Hisaharu Makino, Takafumi Odo, Yoshihisa Iseri, Hiroyuki Tanaka, Kousuke Marutsuka, Akira Nakatani, Hironori Murakami, Yoshiko Shioya, Yutaka Horio, Tsuneo Ikeda, Kazuo Machii, Masanori Kamura, Keiichiro Ban, Yoshihiro Fujii, Kazuo Nishimoto, Susumu Misugi, Tetsuo Munakata, Katsutoshi Yoshimura, Shigetoshi Minami, Takao Nakashima, Hirofumi Ogata, Atuko Hifumi, Nobuko Sakurai, Ryuichiro Tsurusaki, Yoshito Yamanaka, Hiromitsu Yokota, Seishi Ichihara, Motoki Yoshinari, Yoko Sawada, Eiji Kawashima, Kazuo Goto, Yoshimi Kinoshita, Masao Kikukawa, Hiroharu Yamada, Yuya Tanaka, Mayumi Kiyota, Yoshihiro Kimura, Yasuhiro Morikami, Masahiro Fukuda, Takeshi Takami, Fumihiko Nakatani, Shojiro Naomi, Toshiaki Nasu, Tomohiro Sawada, Fuyuki Minagawa, Osamu Haraguchi, Norifumi Kondo, Hiroyuki Shono, Hiromichi Sugiyama, Takeshi Matsuo, Minoru Takaoka, Tamio Nakajima, Masamitsu Toihata, Kozaburo Matsuyama, Kenichi Komori, Toshio Tsubokura, Madoka Taguchi, Yuko Hiramori, Hiroto Okubo, Akihiro Iemura, Osamu Doi, Masayuki Ogihara, Kenji Misumi, Koji Seo, Ken Iwai, Masatoshi Naito, Seiji Ozawa, Kotaro Minoda, Hiromi Fujii, Kimiaki Miwa, Genshi Egusa, Isao Yasuda, Michiaki Ueda, Junichi Miyata, Midori Yoshimura, Masakuni Uemyama, Katumi Watanabe, Yoshikuni Haraguchi, Satoshi Tanazawa, Yoshiaki Osamura, Junji Shibata, Takashi Ono, Syuichi Kamijikkoku, Kazumi Yoshimoto, Etsuo Kinuwaki, Kazuo Kozuma, Kenji Onoue, Yukitaka Nakano, Nanami Abe, Haruo Araki, Kyoji Takaoka, Chieko Imamoto, Hisakazu Suefuji, Keisuke Sugimoto, Terufumi Matsunaga, Akiko Oya, Yoko Onishi, Keizo Kajiwara, Tetsuo Ikuno, Michiaki Doi, Toshiro Igaki, Hiroshi Bando, Tateo Ogura, Kenichi Doijiri, Taisuke Iwaoka, Kazunobu Akahoshi, Kenji Obata, Hisashi Shimono, Kaoru Tsuda, Shinya Yumoto, Keishiro Oka, Hironori Hasegawa, Hisao Fujimoto, Toshiya Atsumi, Akira Matsutani, Yohiyuki Katsuyama, Ryo Fukami, Yoshihisa Iseri, Yutaka Ishibashi, Kiyotaka Kudou, Tetsuo Kuwahara, Kazutaka Maeda, Akira Maki, Naiki Manda, Hirofumi Yasue, Yuji Mizuno, Sueo Momosaki, Koji Tokube, Fumishi Tomita, Tatsuaki Tsuchiya, Matahiro Yabuta, Hidei Yamada

Abstract

Objective: Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events. The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction.

Research design and methods: The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a prospective, randomized, open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases. Patients were assigned to the aspirin group (81 mg/day or 100 mg/day) or the nonaspirin group and followed for a median of 4.37 years. The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease, stroke, and peripheral arterial disease.

Results: The analysis included 2,523 patients who had serum creatinine measured. In 1,373 patients with baseline estimated glomerular filtration rate (eGFR) 60-89 mL/min/1.73 m(2), the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group (aspirin, 30/661; nonaspirin, 55/712; hazard ratio 0.57 [95% CI 0.36-0.88]; P = 0.011). Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥ 90 mL/min/1.73 m(2) (aspirin, 9/248; nonaspirin, 11/270; 0.94 [0.38-2.3]) or those with eGFR <60 mL/min/1.73 m(2) (aspirin, 29/342; nonaspirin, 19/290; 1.3 [0.76-2.4]). The Cox proportional hazard model demonstrated a significant interaction between mild renal dysfunction (eGFR 60-89 mL/min/1.73 m(2)) and aspirin (P = 0.02).

Conclusions: These results suggest a differential effect of low-dose aspirin therapy in diabetic patients with eGFR 60-89 mL/min/1.73 m(2).

Trial registration: ClinicalTrials.gov NCT00110448.

Figures

Figure 1
Figure 1
Percentage of primary end points by category of patients with eGFR of at least 90 mL/min/1.73 m2 (A), 60–89 mL/min/1.73 m2 (B), or <60 mL/min/1.73 m2 (C).
Figure 2
Figure 2
Subgroup analysis of incidence of primary end points.

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Source: PubMed

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