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Erythropoiesis-stimulating agents and cardiovascular events in patients with myelodysplastic syndrome and multiple myeloma

Authors Horváth-Puhó E, Suttorp MM, Frederiksen H, Hoekstra T, Dekkers OM, Pedersen L, Cannegieter SC, Dekker FW, Sørensen HT

Received 25 April 2018

Accepted for publication 29 June 2018

Published 28 September 2018 Volume 2018:10 Pages 1371—1380


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Irene Petersen

Erzsébet Horváth-Puhó,1 Marit M Suttorp,2 Henrik Frederiksen,1,3 Tiny Hoekstra,2 Olaf M Dekkers,1,2 Lars Pedersen,1 Suzanne C Cannegieter,2 Friedo W Dekker,2 Henrik Toft Sørensen1

1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Haematology, Odense University Hospital, Odense, Denmark

Introduction: Erythropoiesis-stimulating agent (ESA) treatment has been associated with an increased risk of venous thromboembolism (VTE) in patients with solid tumors and with an increased risk of cardiovascular events in patients with chronic kidney disease. The ESA-related risk in patients with hematological neoplasms remains unclear. We, therefore, aimed to assess the ESA-related risk of VTE, myocardial infarction (MI), and stroke in patients with multiple myeloma (MM) and myelodysplastic syndrome (MDS).
Materials and methods: We conducted a population-based cohort study in Denmark, using medical databases to identify 2,114 MDS patients and 3,105 MM patients diagnosed in 2004–2013. Incidence rates per 1,000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE, MI, and stroke associated with ESA treatment were computed. HRs were calculated in time-dependent Cox regression and adjusted for age, sex, MDS prognosis group, comorbidities, and treatments.
Results: Incidence rates per 1,000 person-years for VTE, MI, and stroke were 10.8, 8.2, and 16.0 in MDS patients, and 21.9, 10.2 and 9.9 in MM patients without ESA treatment, respectively. MDS patients with ESA treatment had a 1.6-fold increased risk of MI (HR 1.60 [95% CI 0.90–2.86]) and an almost twofold increased risk of stroke (HR 1.94 [95% CI 1.28–2.94]). Adjusted HR for VTE was 1.04 (95% CI 0.57–1.89) compared with MDS patients without ESAs. In MM patients with ESAs compared with patients without ESAs, HRs were 1.41 (95% CI 0.96–2.08) for VTE, 1.23 (95% CI 0.68–2.20) for MI, and 1.63 (95% CI 0.96–2.77) for stroke.
Conclusion: ESA use was associated with stroke in MDS patients. Among MM patients, ESA treatment was associated with a higher risk of all cardiovascular events, although all CIs included equivalence.

Keywords: cohort study, epidemiology, erythropoietin, multiple myeloma, myelodysplastic syndromes, myocardial infarction, stroke, pulmonary embolism, venous thrombosis

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