Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial

Xiaoyi Ning,Guoping Yang,Zhijun Huang,Chengxian Guo,Yun Kuang,Da Miao,Jinlian Xie

doi:10.1007/s00210-020-02037-3

Xiaoyi Ning, Guoping Yang + Show 5 more

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https://doi.org/10.1007/s00210-020-02037-3

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Abstract

This study aimed to analyze the influence of renal insufficiency on the anticoagulant effects and safety of warfarin in Chinese patients. Data on the creatinine levels of participants enrolled in a randomized controlled study were screened and divided into the non-renal insufficiency group, mild renal insufficiency group, and moderate renal insufficiency group, according to the creatinine clearance rate. The primary outcome measures were stable dose and average daily dose of warfarin. Secondary outcome measures were percentage of time in the therapeutic international normalized ratio (INR) (%TTR), and the first time to reach the therapeutic INR. Adverse events included bleeding events, thromboembolic events, and mortality. All participants with renal function test results and a baseline INR of less than 1.5 were included in the primary and secondary outcome analysis. The SPSS Statistics 21.0 software was used for statistical analysis. The randomized controlled trial was registered in Clinicaltrials.gov (NCT02211326). A total of 571 patients were included in this analysis. Multiple regression analysis showed that the renal function was correlated with stable dose, average daily dose, and the first time to reach therapeutic INR after adjusting for confounding factors. However, no correlation was noted between kidney function and %TTR. No significant differences were observed across the various safety parameters among the three groups. Renal function is an important consideration in patients using warfarin.

Highlights

Xiaoyi Ning and Yun Kuang contributed to this work and should be considered joint first authorThe authors confirm that the Principal Investigator for this paper is Guoping Yang and that he had direct clinical responsibility for patients.Warfarin is the most common and effective anticoagulant, used to prevent and treat thromboembolic disease worldwide
The results showed that patients with weaker renal function tended to be older
We have adjusted for age in the multivariate analysis, and the results showed that renal function was correlated with the stable dose and average daily dose after adjusting for confounding factors including age (Table 3 and Table 4)

Summary

Introduction

The authors confirm that the Principal Investigator for this paper is Guoping Yang and that he had direct clinical responsibility for patients. Warfarin is the most common and effective anticoagulant, used to prevent and treat thromboembolic disease worldwide. S-warfarin, which exerts the main anticoagulant effect, is mainly metabolized by CYP2C9 into S-6 and S-7 hydroxyl products. R-warfarin is mainly metabolized by CYP1A2, CYP3A4, and CYP2C19 into R-8 warfarin. Warfarin is almost entirely metabolized by the liver. The hydroxyl products, which have weak anticoagulant effects, are mainly excreted by the kidney, and only a small amount of the prototype drug is excreted in the urine. No dose adjustment of warfarin is needed in patients with chronic kidney disease (CKD). The warfarin prescribing information does not specify dosage recommendations guided by renal function

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