Differential prediction of high-sensitivity cardiac troponin-I, but not N-terminal pro-brain natriuretic peptide, in different pitavastatin doses on cardiovascular events in stable coronary artery disease.

Background: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin.
Methods: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline.
Results: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001).
Conclusions: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.
Competing Interests: Declaration of Competing Interest Dr. J. Ishii received a research grant from Sysmex Corp. and honoraria from Daiichi Sankyo Co. Ltd., Kowa Pharmaceutical Co. Ltd., Siemens Healthineers Japan, and LSI Medience Corp. Dr. Fukumoto received research grant from Sanofi KK, Shionogi & Co, Ltd., honoraria from Public Health Research Foundation, AstraZeneca KK, Eisai Co, Ltd., Kowa Pharmaceutical Co Ltd., research grant and honoraria from MSD KK, Otsuka Pharmaceutical Co, Ltd., Daiichi Sankyo Co, Ltd., Sumitomo Dainippon Pharma Co, Ltd., Teijin Pharma Ltd., Bayer Yakuhin, Ltd., Mochida Pharmaceutical Co, Ltd., Astellas Pharma Inc., Sanwa Kagaku Kenkyusho Co, Ltd., Takeda Pharmaceutical Co Ltd., Mitsubishi Tanabe Pharma Corp, Pfizer Japan Inc., Ono Pharmaceutical Co Ltd., AstraZeneca KK. Dr. Ozaki received research grant and honoraria from Mochida Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited, Sanofi K.K., Shionogi & Co., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., research grant, other reserch support and honoraria from Public Health Research Foundation. Dr. Iimuro received research grant from Amgen Astellas BioPharma K.K., research grant and honoraria from Public Health Research Foundation. Dr. Iwata received other research support from Public Health Research Foundation, honoraria from Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company Limited, MSD K.K., Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Dr. Sakuma received honoraria from GlaxoSmithKline, AstraZeneca, Takeda, Bayer, Pfizer, Bristol-Myers Squibb, Boehringer lngelheim, MSD, Kyowa Hakko Kirin, Daiichi Sankyo, Novartis, Sanofi, Kowa, Shionogi, Kissei, Astellas, Amgen, Ono, Otsuka, Novonordisk, Mochida, Teijin, Sysmex, Nipro, Kyorin, Fuji and Sumitomo Dainippon, research grants from Public Health Research Foundation, Kowa, National Cerebral and Cardiovascular Center and Medical Informatics Study Group. Dr. Nakagawa received honoraria from Kowa Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Bayer Yakuhin, Ltd., Sanofi K.K., Daiichi Sankyo Company, Limited, Shionogi & Co., Ltd., Astellas Pharma Inc., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., AstraZeneca K.K., Amgen Astellas BioPharma K.K., Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., research grant, other research support and honoraria from Public Health Research Foundation. Dr. Hibi received research grants from Public Health Research Foundation, Abott Vascular Japan Co. Ltd., and Sanofi KK. Dr. Hiro received research grants from Otsuka Pharmaceutical Co. Ltd., Shionogi & Co. Ltd., and Takeda Pharmaceutical Co. Ltd., honoraria from Amgen Astellas BioPharma KK, Kowa Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., and Chugai Pharmaceutical Co. Ltd., research grants and honoraria from Astellas Pharma Inc., Eisai Co. Ltd., MSD KK, Sanofi KK, Daiichi Sankyo Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Bayer Yakuhin, Ltd., Pfizer Japan Inc., and AstraZeneca KK, and research grant, other research support, and honoraria from Public Health Research Foundation. Dr. Hokimoto received honoraria from Daiichi Sankyo Co. Ltd. and AstraZeneca KK. Dr. Miyauchi received honoraria from Sanofi KK, Daiichi Sankyo Co. Ltd., AstraZeneca KK, Amgen Astellas BioPharma KK, Takeda Pharmaceutical Co. Ltd., Bayer Yakuhin, Ltd., and MSD KK. Dr. Daida received honoraria from Amgen Astellas BioPharma KK, Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co., Ltd., MSD KK, and research grant from Canon, and scholarship grant from Otsuka Pharmaceutical Co., Ltd., Sanofi KK, MSD KK, Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corp., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Shionogi & Co., Ltd., Actelion Pharmaceuticals Japan, Ltd. Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan Co., Ltd., and courses endowed by Phillips, Resmed, Fukuda Denshi, Asahikasei, Inter-Reha. Dr. Shimokawa received research grant from Shionogi & Co, Ltd., Teijin Pharma Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co, Ltd., honoraria from Kowa Pharmaceutical Co Ltd., Sanofi KK, AstraZeneca KK, Bayer Yakuhin, Ltd., research grant and honoraria from MSD KK, Mitsubishi Tanabe Pharma Corp, Daiichi Sankyo Co, Ltd., research grant, other research support, and honoraria from Public Health Research Foundation. Dr. Saito received honoraria from Otsuka Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., Mochida Pharmaceutical Co. Ltd., and Kowa Pharmaceutical Co. Ltd. and other research support and honoraria from Public Health Research Foundation. Dr. Kimura received research grant from Sumitomo Dainippon Pharma Co, Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corp, Takeda Pharmaceutical Co Ltd., other research support and honoraria from Kowa Pharmaceutical Co Ltd., Bayer Yakuhin, Ltd., research grant, other research support, and honoraria from MSD KK, Sanofi KK, Mochida Pharmaceutical Co, Ltd., Daiichi Sankyo Co, Ltd., Public Health Research Foundation, Amgen Astellas BioPharma KK. Dr. Matsuzaki received honoraria from Mochida Pharmaceutical Co. Ltd. Dr. Nagai received honoraria from Kowa Pharmaceutical Co Ltd., Takeda Pharmaceutical Co Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co, Ltd., Shionogi & Co, Ltd., MSD KK, Mitsubishi Tanabe Pharma Corp, Amgen Astellas BioPharma KK, Eisai Co, Ltd., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co, Ltd., Mochida Pharmaceutical Co, Ltd., honoraria and expert witness from Public Health Research Foundation. Other coauthors report no conflicts.
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