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Cancer is Associated with an Increased Stroke Risk in Patients with Atrial Fibrillation and CHA2DS2VASc Score ≤ 2

A. Leader1,2, N. Mendelson Cohen3, S. Afek2,4, R. Jaschek3, A. Frajman2, O. Itzhaki Ben Zadok5,2, P. Raanani1,2, M. Lishner6,2, A. Tanay3, G. Spectre1,2

1Institute of Hematology, Davidoff Cancer Centre, Rabin Medical Centre, Petah Tikva, Israel, 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel, 4Department of Family Medicine, Sharon-Shomron District, Clalit Health services, Netanya, Israel, 5Department of Cardiology, Rabin Medical Centre, Petah Tikva, Israel, 6Research Institute, Meir Medical Centre, Kfar Saba, Israel

Abstract Number: OC 65.1

Meeting: ISTH 2021 Congress

Theme: Arterial Thromboembolism » Cardiovascular Risk Factors

Background: It is unclear whether cancer adds to the risk of arterial thromboembolism (ATE) in atrial fibrillation (AF). This is especially relevant for low-intermediate CHA2DS2VASc scores, where risk-benefit ratios between ATE and bleeding are delicately balanced.

Aims: Evaluate ATE risk in AF patients with a low-intermediate CHA2DS2VASc score, with/without cancer.

Methods: A population-based historical cohort study of the Clalit Health Services (CHS) database (1.1.2005–31.12.2020). Patients ≥20 years, with CHA2DS2VASc ≤2, not receiving anticoagulation at study index, were included. Experimental groups included patients with atrial fibrillation/flutter (ICD-9 codes) at/prior study index. The study exposure was newly diagnosed cancer (ICD-9 codes). Patients with embolic ATE or cancer, prior study index, were excluded.
Patients were classified into 4 cohorts: “AF&cancer” (exposed), “AF&no-cancer” (unexposed), “cancer&no-AF” (positive control) and “no-AF&no-cancer” (negative control). Cohorts were matched for multinomial distribution of age, sex, index year, AF duration, CHA2DS2VASc score and low/high/undefined ATE-risk cancer. Cancers were classified as high ATE risk if 12-month ATE incidence was ≥5% in prior studies. Patients were followed from study index (date of cancer or matched date) until primary outcome or death.
The primary outcome was acute embolic ATE (ischemic stroke, transient ischemic attack (TIA) or systemic ATE), using ICD-9 codes from hospitalization. Cox proportional hazards multivariate regression was used to calculate the hazard ratio (HR) for the primary outcome at 12 months (death as competing risk).

Results: The study included 28420 patients. Table 1 shows baseline characteristics. The ATE incidence is shown in Figure 2. The risk of embolic ATE was highest in AF&cancer, compared to AF&no-cancer (HR 2.86 [95% CI: 1.75-4.69]) and to cancer&no-AF (2.86 [1.86-4.39]).

Table 1: Patient characteristics
Variable (at index) AF & Cancer, n (%) (n=1490) AF & no-cancer, n (%) (n=4368) Cancer & no-AF, n (%) (n=2908) no-AF & no-cancer, n (%) (n=19654)
Age (years), median (IQR) 65 (60-71) 64 (59-70) 65 (59-70) 64 (59-71)
Male sex 1110 (74.5) 3228 (73.9) 2148 (73.9) 14489 (73.7)
BMI, median (IQR) 27.1 (24.2-30.3) 27.3 (24.6-30.7) 26.6 (23.9-29.7) 27.1 (24.4-30.1)
Dyslipidemia 728 (48.9) 2067 (47.3) 1324 (45.5) 7991 (40.7)
CHADS2VASc2 = 2 865 (58.1) 2493 (57.1) 1658 (57.0) 11152 (56.7)
Chronic cardiovascular disease 124 (8.3) 306 (7.0) 137 (4.7) 698 (3.6)
Aspirin 646 (43.4) 1869 (42.8) 707 (24.3) 4267 (21.7)
Duration of AF prior index (months), median (IQR) 26.1 (1.9-60.1) 21.0 (1.5-59.7) Not relevant Not relevant
Antiarrhythmic medication 317 (21.3) 937 (21.5) 9 (0.3) 66 (0.3)

Patient characteristics

 Cumulative incidence of ATE

Conclusions: Cancer patients with AF and low-intermediate CHA2DS2VASc score have a higher risk of stroke, TIA or systemic ATE than non-cancer patients with AF. Risk/benefit of anticoagulation in this population should be studied.

To cite this abstract in AMA style:

Leader A, Mendelson Cohen N, Afek S, Jaschek R, Frajman A, Itzhaki Ben Zadok O, Raanani P, Lishner M, Tanay A, Spectre G. Cancer is Associated with an Increased Stroke Risk in Patients with Atrial Fibrillation and CHA2DS2VASc Score ≤ 2 [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/cancer-is-associated-with-an-increased-stroke-risk-in-patients-with-atrial-fibrillation-and-cha2ds2vasc-score-%e2%89%a4-2/. Accessed May 20, 2022.

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