Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy
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)
- et al.
A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey
Chest
(2010) - et al.
Relation between cancer and atrial fibrillation (from the Reasons for Geographic and Racial Differences in Stroke Study)
Am. J. Cardiol.
(2015) - et al.
Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database
Ann. Thorac. Surg.
(2010) - et al.
Atrial fibrillation after operation for lung cancer: clinical and prognostic significance
Ann. Thorac. Surg.
(1999) - et al.
Colorectal cancer and atrial fibrillation: a case–control study
Am. J. Med.
(2002) - et al.
Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis
Thromb. Res.
(2006) - et al.
Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care
Lancet
(1997) - et al.
Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis
Blood
(2002) - et al.
Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study
Heart
(2001) - et al.
Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study
JAMA
(2001)
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
Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study
J. Cardiothorac. Surg.
Diseases preceding colon cancer. A case–control study among veterans
Dig. Dis. Sci.
First diagnosis of colorectal or breast cancer and prevalence of atrial fibrillation
Intern. Emerg. Med.
Cited by (40)
Optimizing antithrombotic therapy for atrial fibrillation in cancer
2022, Thrombosis ResearchCitation 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].
Risk of Cardioembolic Stroke in Patients With Cancer and Atrial Fibrillation
2018, American Journal of CardiologyOral anticoagulation therapy in the elderly population with atrial fibrillation. A review article
2018, Revista Espanola de Geriatria y GerontologiaCancer-associated venous thromboembolism – treatment and prevention
2023, Cardiologia Hungarica