Elsevier

International Journal of Cardiology

Volume 203, 15 January 2016, Pages 372-378
International Journal of Cardiology

Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy

https://doi.org/10.1016/j.ijcard.2015.10.166Get rights and content

Abstract

Background

The efficacy of oral anticoagulation therapy (OAT) has not been revealed in atrial fibrillation (AF) patients with newly diagnosed cancers. This study evaluated the thromboembolic and bleeding events in AF patients with malignancies according to OAT.

Methods and results

In 2168 consecutive non-valvular AF patients with newly diagnosed malignancies, we analyzed the composite endpoints including major adverse cardiac events (MACEs) and major bleeding. Based on a propensity score matching, two groups with 690 matched pairs were created.

Patient baseline characteristics were comparable between the matched groups. During a follow-up period of 3.9 ± 2.8 years, 72 (10%) and 65 (9%) patients had MACEs in the propensity score-matched OAT + and OAT − groups, respectively (p = 0.461). There was no significant difference in the major bleeding (10% vs. 8%, p = 0.300) and composite endpoints (18% vs. 16%, p = 0.181) between OAT + and OAT − patients. During the first year after the cancer diagnosis, 66 (48%) MACEs, 52 (41%) major bleedings, and 116 (49%) composite end points of all events occurred. The optimal international normalized ratio (2.0 to 3.0) level was achieved in only 85 (12%) patients. However, 1 year after cancer diagnosis, OAT + patients with the target therapeutic range of ≥ 60% demonstrated better cumulative survival free of composite end point than OAT − patients (p = 0.026).

Conclusion

During the first year after the cancer diagnosis, OAT did not improve the composite end point because of poor INR control caused by cancer treatment. However, after 1 year after diagnosis of cancer, optimal anticoagulation significantly reduced the composite end point.

Introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1–2% of the general population [1], [2]. AF confers a 5-fold risk of a stroke, and one in five of all strokes are attributed to this arrhythmia. Multiple clinical trials have demonstrated the superior therapeutic effect of vitamin K antagonists (VKAs) compared to a placebo in the prevention of thromboembolic events among patients with non-valvular AF [3]. However, AF patients with comorbidities such as end stage renal disease, bleeding, and malignancy have the concomitant risk of fatal bleeding, which causes clinicians to be reluctant to use VKAs in spite of the high stroke risk [4].

AF is common in patients with life-threatening cancer and those undergoing active cancer treatments [5]. The development of AF after cancer surgery is well known [6], [7], [8]. Several studies have suggested that the association between cancer and AF is not limited to the postoperative period [9], [10], [11], [12], [13]. Despite the excellent effect of VKAs in the prevention of thromboembolisms, OAT might result in an elevated bleeding risk in patients with cancer and a history of non-valvular AF [14]. Moreover, the effect of the OAT according to the time duration, and treatment modalities of cancer has not been revealed.

We hypothesized that OAT in patients with newly diagnosed cancer and previous AF would result in an increase in major bleeding and a decrease of thromboembolic events. The aim of this study was to evaluate the clinical course, including thromboembolic and bleeding events, in patients with cancer and a history of AF according to whether or not they received OAT.

Section snippets

Patients

The study protocol was approved by the Institutional Review Board of Severance Cardiovascular Hospital, Seoul, Korea and complied with the Declaration of Helsinki. From November 2005 to January 2015, using the International Classification of Disease, Ninth Revision, codes, we identified 2168 consecutive patients with non-valvular AF and cancer. Patients who underwent radiofrequency catheter ablation (RFCA) or cardioversion (n = 7) and who had insufficient clinical data (n = 43) were excluded (Fig. 1

Patient characteristics

The clinical characteristics of the OAT + and OAT − groups are presented in Table 1. Compared with the OAT − group, the OAT + group was composed of more female patients (64% vs. 73%, p < 0.001), had a higher prevalence of hypertension (75% vs. 57%, p < 0.001), diabetes (38% vs. 30%, p < 0.001), a history of a stroke/transient ischemic attacks (12% vs. 3%, p < 0.001), and a history of brain hemorrhages (2% vs. 1%, p < 0.001). The CHA2DS2-VASc (3.5 ± 1.5 vs. 2.7 ± 1.4, p < 0.001) and HAS-BLED (4.1 ± 1.4 vs. 2.5 ± 1.5, p <

Major findings

In non-valvular AF patients with newly diagnosed cancer, since INR was poorly controlled within 1 year after cancer diagnosis due to cancer treatment and comorbidities, OAT did not improve MACEs, major bleeding, and composite end points. Almost half of the all MACEs and major bleeding events occurred within the first year after the diagnosis of cancer in AF patients. However, after 1 year from cancer diagnosis, OAT + patients who achieved TTR ≥ 60% for INR had a better composite end point than OAT 

Conclusion

In AF patients with newly diagnosed malignancy, the composite end point including MACEs and major bleeding was not improved by optimal OAT within a year after cancer diagnosis. However, after 1 year from diagnosis of cancer, maintaining optimal INR reduced the composite endpoint. Our study suggests that OAT should be considered, a year after cancer diagnosis.

Sources of funding

This study was supported in part by research grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2012R1A2A2A02045367), and a grant from the Korean Healthcare technology R&D project funded by Ministry of Health & Welfare (HI12C1552).

Financial/Conflict of Interest Disclosure

The authors have no funding, financial relationships, or conflicts of interest to disclose.

References (28)

  • K.L. Furie et al.

    Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

    Stroke

    (2011)
  • A. Imperatori et al.

    Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study

    J. Cardiothorac. Surg.

    (2012)
  • A.D. Muller et al.

    Diseases preceding colon cancer. A case–control study among veterans

    Dig. Dis. Sci.

    (1994)
  • S. Guzzetti et al.

    First diagnosis of colorectal or breast cancer and prevalence of atrial fibrillation

    Intern. Emerg. Med.

    (2008)
  • Cited by (40)

    • Optimizing antithrombotic therapy for atrial fibrillation in cancer

      2022, Thrombosis Research
      Citation Excerpt :

      In a recent retrospective study of 2168 consecutive patients with AF and cancer followed for an average of 4 years, no significant difference was observed in the composite end-point of major adverse cardiac events (ischemic stroke, myocardial infarction, and pulmonary embolism) or major bleeding in patients treated with VKAs, when compared to those who were not anticoagulated. However, only 12% of patients on VKA therapy achieved a therapeutic INR, and the difficulty of maintaining effective anticoagulation likely contributed to the lack of treatment benefit [46]. In a large population of veterans taking VKAs for AF or for VTE, warfarin laboratory control worsened significantly over a period of 6 months following a new diagnosis of cancer, compared to no oncologic patients [47].

    View all citing articles on Scopus
    View full text