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Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

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Abstract

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1–2, 3–4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.

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Abbreviations

NOAC:

Non-vitamin K antagonist oral anticoagulants

NVAF:

Non-valvular atrial fibrillation

AF:

Atrial fibrillation

eCCr:

Estimated creatinine clearance

CKD:

Chronic kidney disease

CHF:

Congestive heart failure

TIA:

Transient ischemic attack

OR:

Odds ratio

CI:

Confidence interval

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Acknowledgments

This work was supported by a grant from Japan Cardiovascular Research Foundation (Miyamoto); a grant from a Grant-in-Aid for Scientific Research on Innovative Areas (25136727, Aiba); a Grant-in-Aid for Scientific Research (C) (24591086 Aiba) from MEXT of Japan; Intramural Research Fund (25-4-7, Kusano) for Cardiovascular Diseases of National Cerebral and Cardiovascular Center; Health and Labour Sciences Research Grants (H26 Iryoukiki Ippan 019) Ministry of Health, Labour and Welfare, Japan (Kusano).

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Authors and Affiliations

  1. Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishiro-dai, Suita, Osaka, 565-8565, Japan

    Koji Miyamoto, Takeshi Aiba, Kohei Ishibashi, Sayako Hirose, Mitsuru Wada, Ikutaro Nakajima, Hideo Okamura, Takashi Noda, Teruo Noguchi, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Wataru Shimizu & Kengo Kusano

  2. Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Koji Miyamoto, Hideo Okamura, Toshihisa Anzai, Satoshi Yasuda, Wataru Shimizu & Kengo Kusano

  3. Division of Stroke Care Unit, National Cerebral and Cardiovascular Center, Suita, Japan

    Shoji Arihiro

  4. Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan

    Makoto Watanabe, Yoshihiro Kokubo & Yoshihiro Miyamoto

  5. Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan

    Kazuyuki Nagatsuka

  6. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Hisao Ogawa

  7. Department of Cardiovascular Medicine, Nippon Medical School, Bunkyō, Japan

    Wataru Shimizu

  8. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan

    Kazunori Toyoda

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  1. Koji Miyamoto
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  2. Takeshi Aiba
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  4. Makoto Watanabe
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  18. Wataru Shimizu
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  19. Yoshihiro Miyamoto
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  20. Kazunori Toyoda
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  21. Kengo Kusano
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Correspondence to Takeshi Aiba or Kengo Kusano.

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Conflict of interest

Dr. Koji Miyamoto received lecture fees/honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers, Pfizer, and Daiichi-Sankyo. Dr. Aiba received lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers, and Pfizer. Dr. Ishibashi received lecture fees/honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers, and Pfizer. Dr. Yasuda received lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers, Pfizer, and Daiichi-Sankyo. Dr. Shimizu received lecture fees/honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers, Pfizer, and Daiichi-Sankyo. Dr. Ogawa received lecture fees/honoraria from Boehringer Ingelheim. Dr. Toyoda received lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers, and Pfizer. Dr. Kusano received lecture fees from Bayer, Boehringer Ingelheim, and Bristol-Myers. Dr. Kamakura received research funds from Boehringer Ingelheim and Daiichi-Sankyo. Dr. Ogawa received research funds from Bayer, Bristol-Myers, Daiichi-Sankyo, and Pfizer. Dr. Shimizu received scholarship funds from Bayer, Boehringer Ingelheim, Bristol-Myers, Pfizer, and Daiichi-Sankyo.

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Miyamoto, K., Aiba, T., Arihiro, S. et al. Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Heart Vessels 31, 1327–1336 (2016). https://doi.org/10.1007/s00380-015-0725-6

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