Efficacy of rivaroxaban for the treatment of Chinese patients with acute pulmonary embolism: A retrospective study.

ABSTRACT: Pulmonary embolism (PE) is a life-threatening disease, which accounts for the major type of venous thromboembolism. Currently, there is limited understanding and management for PE. Rivaroxaban is reported to treat patients with PE. However, there is still insufficient evidence on rivaroxaban for the treatment of Chinese patients with acute PE. Thus, this retrospective study investigated the benefits and safety of rivaroxaban for Chinese patients with acute PE.A total of 72 Chinese patient cases with acute PE were analyzed in this study. Of these, 36 cases who received rivaroxaban mono-therapy were assigned to the treatment group, while the remaining 36 cases who received standard therapy were assigned to the control group. The benefits were assessed by the duration of hospital stay, treatment satisfaction, and safety.After treatment, rivaroxaban mono-therapy showed better benefits in decreasing the duration of hospital stay (P < .01), increasing treatment satisfaction (P < .01), and reducing mild bleeding (P = .02) in Chinese patients with acute PE, than standard therapy.The results of this study indicated that rivaroxaban may provide more benefits than the standard therapy for Chinese patients with acute PE. Future studies are still needed to warrant the current results.

Introduction

Venous thromboembolism (VTE) is a very common and fatal disease worldwide.[ It often consists of deep vein thrombosis (DVT) and pulmonary embolism (PE).[ Of those, PE is a life-threatening disorder, which is one of the most leading causes of high mortality and morbidity.[ It is reported that its incidence is about 69 cases per 100,000 people annually.[ Other studies reported that its incidence rate varies from 19.7% to 25% in patients aged under 50 years old,[ compared with that ranges from 25% to 62% in subjects below 65 years old.[ Studies also reported that its death rate ranges between 20% and 65% within 1 hour of its onset,[ and it is still about 5% up to the 12 months post PE.[

During the past few decades, the vitamin K antagonist (VKA) warfarin has been utilized for the treatment of patients with PE.[ However, its efficacy and safety are restricted. Fortunately, non-VKA rivaroxaban is found to benefit patients with PE. It is an anticoagulant and a direct Factor Xa inhibitor.[ Compared with VKAs, rivaroxaban has several merits for PE, such as rapid onset of action, and a satisfied pharmacokinetic profile without routine lab monitoring of international normalized rate (INR).[ Previous studies have tested the efficacy and safety of rivaroxaban in treating patients with PE.[ However, there is still limited evidence on Chinese patients with acute PE. Thus, this retrospective study aimed to investigate the efficacy and safety of rivaroxaban for Chinese patients with acute PE.

Patients and methods

Ethical consideration

This retrospective study was approved by the ethics medical committee of The First Affiliated Hospital of Jiamusi University. All participants provided the written informed consent.

Design

This study was designed as a retrospective study. All cases were collected from The First Affiliated Hospital of Jiamusi University between June 2017 and April 2019. A total of 72 cases with acute PE were analyzed. They were equally assigned to the treatment group and the control group according to the different treatments they received. Patients in the treatment group received rivaroxaban mono-therapy, while subjects in the control group underwent standard therapy. This retrospective study did not apply randomization. In addition, it also did not utilize blind process to both patients and researchers. However, the data analyst was blinded in this study. All outcomes were measured and analyzed after treatment. No further follow-visits were recorded.

Patients

The eligible acute PE cases with or without symptomatic DVT were diagnosed by multidetector computed tomographic (CT), ventilation/perfusion lung scan, or selective CT pulmonary angiography. All included patients aged between 18 and 70 years old.

Cases were excluded if the patients received at least 1 anticoagulant treatment, except the rivaroxaban; other therapies for treating PE that affected the rivaroxaban, such as surgical thromboectomy, or vena cava filter placement surgery; active or highly risk of bleeding; or history of hematological diseases; severe renal disease; severe hepatic failure; allergy to the study medication; pregnancy or lactation; psychological conditions that may affect the outcome assessment; received study medication 1 month before this study treatment; and insufficient essential patient information.

Treatment schedule

The cases in the treatment group received rivaroxaban 15 mg initially, twice daily over the first 21 days, then followed by 20 mg once daily for the remaining 3 months. If the risk of bleeding over the risk of identified recurrent VTE, the dosage was decreased from 20 to 15 mg once daily.

The cases in the control group were given standard therapy. It comprised of enoxaparin 100 ug/kg, twice daily, and then overlapping followed by an empiric-dose of warfarin. VKA was utilized and its dosage was adjusted to maintain the INR between 2.0 and 3.0. Additionally, INR was determined at least monthly.

Outcome measurements

The primary outcome was duration of hospital stay. The secondary outcomes included treatment satisfaction and safety. The treatment satisfaction was measured by the generic Treatment Satisfaction Questionnaire for Medication version II (TSQM II).[ It comprises 4 subscales of effectiveness, side-effects, convenience, and global satisfaction with a total of 10 items. Each item ranges from 0, extremely dissatisfied, to 4, extremely satisfied, with higher score indicating better treatment satisfaction.[ All item scores were converted to a score between 0 and 100 in this study. Safety includes anti-coagulant-induced bleeding, PE-related death, and stroke.

Statistical analysis

The characteristic values and outcome data were analyzed by the SAS package (Version 9.1; SAS Institute Inc, Cary, NC). The continuous data were analyzed by t test or Wilcoxon test, while the categorical data were performed by the Pearson χ2 test or Fisher exact test. The statistical significance level was defined as P < .05.

Results

The general characteristic values of included cases from both groups are listed in Table 1. There were no significant differences regarding all characteristic values between 2 groups.

Table 1

Comparison of patient characteristics between 2 groups.

Characteristics	Treatment group (n = 36)	Control group (n = 36)	P value
Mean age (year)	51.9 (12.0)	53.5 (12.7)	.58
Gender
Male	21 (58.3)	19 (52.8)	.64
Female	15 (41.7)	17 (47.2)	.64
Race (China)	36 (100.0)	36 (100.0)	–
BMI (kg/m2)	23.8 (2.5)	23.4 (3.0)	.54
Risk factor associated with VTE
Recent surgery or trauma	7 (19.4)	5 (13.9)	.53
Previous VTE	6 (16.7)	8 (22.2)	.55
Active cancer	2 (5.6)	3 (8.3)	.65
Estrogen therapy	4 (11.1)	5 (13.9)	.72
Immobilization	6 (16.7)	4 (11.1)	.50
Known thrombophilic condition	2 (5.6)	0 (0)	.29
Unprovoked VTE	18 (50.0)	21 (58.3)	.48
Comorbidity
Heart failure	1 (2.8)	0 (0)	.49
COPD or asthma	3 (8.3)	4 (11.1)	.69
Ischemic heart disease	3 (8.3)	2 (5.6)	.65
Stroke	0 (0)	1 (2.8)	.49

Data are present as mean ± standard deviation or number (%).

BMI = body mass index, COPD = chronic obstructive pulmonary disease, VTE = venous thromboembolism.

The results showed that patients in the treatment group benefited more in duration of hospital stay (P = .04, Table 2), and treatment satisfaction, measured by TSQM II scale (effectiveness, P < .01; side-effects, P = .02; convenience, P < .01; global satisfaction, P < .01; Table 3), than patients in the control group.

Table 2

Comparison of duration of hospital stay between 2 groups.

Outcomes	Treatment group (n = 36)	Control group (n = 36)	P value
Duration of hospital stay (days)	10.2 (3.5)	12.0 (4.0)
Difference between groups		−1.8 (−2.9, −0.9)	.04

Data are present as mean ± standard deviation (range).

Table 3

Comparison of treatment satisfaction between 2 groups.

TSQM II	Treatment group (n = 36)	Control group (n = 36)	P value
Effectiveness (2 items)	74.5 (7.2)	68.7 (7.7)	<.01
Side-effects (3 items)	85.7 (8.1)	81.3 (7.5)	.02
Convenience (3 items)	80.9 (6.8)	72.5 (7.3)	<.01
Global satisfaction (2 items)	78.4 (5.9)	72.3 (6.6)	<.01

Data are present as mean ± standard deviation.

TSQM II = Treatment Satisfaction Questionnaire for Medication version II.

Furthermore, there were no significant differences in safety of severe bleeding (P = .49, Table 4), major bleeding (P = .56, Table 4), PE-related death (P = .56, Table 4), and stroke (P = .56, Table 4), except the mild bleeding (P = .02, Table 4) between 2 groups.

Table 4

Comparison of safety between 2 groups.

Safety	Treatment group (n = 36)	Control group (n = 36)	P value
Severe bleeding	0 (8.1)	1 (11.3)	.49
Major bleeding	1 (4.8)	2 (6.5)	.56
Mild bleeding	6 (3.2)	15 (6.5)	.02
PE related death	1 (1.6)	2 (4.8)	.56
Stroke	2 (1.6)	1 (4.8)	.56

Data are present as number (%).

PE = pulmonary embolism.

Discussion

This retrospective study explored the benefits and safety of rivaroxaban for Chinese patients with acute PE. To our best knowledge, insufficient data are still available regarding the rivaroxaban for the treatment of acute PE in individuals in China. In this study, the findings showed that rivaroxaban treatment achieved promising benefits in Chinese patients with acute PE.

Although several studies evaluated the efficacy of rivaroxaban for PE previously, few data are available in Chinese patients with acute PE.[ Two studies conducted in Germany showed that early discharge and out-of-hospital treatment may benefit for patients with acute PE for cost-saving,[ and also provide the simple Pulmonary Embolism Severity Index score to identify low risk of patients with PE.[ One study that was performed in Japan found that PE not only decreased length of hospital stay, but also reduced the burden for both patients and health-care system.[ Three international multicenter clinical trials which were conducted by the Netherlands, Germany, UK, USA, and Brazil found that rivaroxaban may help to improve treatment satisfaction, and reduce treatment cost by decreasing the length of hospital stay.[ Another study that run in China explored the potential efficacy of rivaroxaban mono-therapy versus standard therapy specifically through the dosage adjusting for the warfarin with CYP2C9 and VKORC1 genotypes.[ Its results also showed shorter hospital stay after rivaroxaban mono-therapy.[

The results of the present study are partly consistent with the previous studies.[ In this study, our results showed that rivaroxaban mono-therapy benefited not only for decreasing hospital stay, and improving the treatment satisfaction, but also for reducing mild bleeding, when compared with standard therapy. Its results indicated that rivaroxaban mono-therapy may benefit Chinese patients with acute PE more than the standard therapy did.

Several limitations still exist in the present study. First, this retrospective study did not apply randomization and blinding procedure, which may increase the risk of case selection. Second, this study was conducted in a single center. Thus, further studies should be designed to conduct in multiple centers. Third, this study only assessed the benefits and safety after treatment, and it did not include further follow-up assessment. Finally, the sample size of this study was pretty small, which may affect its findings. Future studies should avoid all above limitations.

Conclusion

The results of this study found that rivaroxaban may benefit more for patients with acute PE than the standard therapy did. Further studies are still needed to warrant the results of the present study.

Author contributions

Conceptualization: Lei Wang, Zhi Xu, Ying Chen.

Data curation: Lei Wang, Zhi Xu, Ying Chen.

Formal analysis: Lei Wang, Shuang Jiang, Chao Li.

Funding acquisition: Ying Chen.

Investigation: Ying Chen.

Methodology: Lei Wang, Shuang Jiang.

Project administration: Ying Chen.

Resources: Lei Wang, Shuang Jiang, Chao Li, Zhi Xu.

Software: Lei Wang, Shuang Jiang, Zhi Xu.

Supervision: Ying Chen.

Validation: Lei Wang, Shuang Jiang, Chao Li, Ying Chen.

Visualization: Lei Wang, Zhi Xu, Ying Chen.

Writing – original draft: Lei Wang, Shuang Jiang, Chao Li, Zhi Xu, Ying Chen.

Writing – review & editing: Lei Wang, Shuang Jiang, Chao Li, Zhi Xu, Ying Chen.