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Cardiovascular Safety of Anagrelide Hydrochloride versus Hydroxyurea in Essential Thrombocythaemia.

ABSTRACT: Essential thrombocythaemia (ET) is a rare myeloproliferative neoplasm. This multicentre, Phase 3b, randomised, open-label, non-inferiority study investigated the cardiac safety, efficacy and tolerability of first-line treatment with anagrelide or hydroxyurea in high-risk ET patients for up to 3 years. Eligible patients aged???18 years with a diagnosis of high-risk ET confirmed by bone marrow biopsy within 6 months of randomisation received anagrelide (n?=?75) or hydroxyurea (n?=?74), administered twice daily. Treatment dose for either compound was titrated to the lowest dose needed to achieve a response. Planned primary outcome measures were change in left ventricular ejection fraction from baseline over time and platelet count at Month 6. Planned secondary outcome measures were platelet count change from baseline at Months 3 and 36; percentage of patients with complete or partial response; time to complete or partial response; number of patients with thrombohaemorrhagic events; and changes in white blood cell count or red blood cell count over time. Neither treatment altered cardiac function. There were no significant differences in adverse events between treatment groups, and no reports of malignant transformation. The incidence of disease-related thrombotic or haemorrhagic events was numerically higher in anagrelide-treated patients. Both treatments controlled platelet counts at 6 months, with the majority of patients experiencing complete or partial responses. In conclusion, these results suggest that long-term treatment with anagrelide is not associated with adverse effects on cardiac function. This is one of the few studies using left ventricular ejection fraction assessment and central biopsy reading to confirm the diagnosis of ET.Trial registration number: Clinicaltrials.gov NCT00202644.

SUBMITTER: Gotic M

PROVIDER: S-EPMC7847982 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Cardiovascular Safety of Anagrelide Hydrochloride versus Hydroxyurea in Essential Thrombocythaemia.

Gotic Mirjana M Egyed Miklos M Gercheva Liana L Warzocha Krzysztof K Kvasnicka Hans Michael HM Achenbach Heinrich H Wu Jingyang J

Cardiovascular toxicology 20201029 3

Essential thrombocythaemia (ET) is a rare myeloproliferative neoplasm. This multicentre, Phase 3b, randomised, open-label, non-inferiority study investigated the cardiac safety, efficacy and tolerability of first-line treatment with anagrelide or hydroxyurea in high-risk ET patients for up to 3 years. Eligible patients aged ≥ 18 years with a diagnosis of high-risk ET confirmed by bone marrow biopsy within 6 months of randomisation received anagrelide (n = 75) or hydroxyurea (n = 74), administere ...[more]

PMID: 33123978

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Project description:BackgroundThe median age of patients diagnosed with essential thrombocythaemia (ET) is 65-70 years but the management of very elderly patients (aged >80 years) with ET has not been well characterized.ObjectiveThis study aimed to document the treatment patterns of very elderly patients with ET in a multinational, real-world setting.Study designEXELS (Evaluation of Xagrid Efficacy and Long-term Safety) is a phase IV observational study, designed to monitor the efficacy and safety of cytoreductive therapies in clinical practice. In total, 3,598 high-risk patients with ET were recruited from May 2005 to April 2009, in 13 European countries. Data were collected at registration and every 6 months thereafter for 5 years. This analysis was performed on a data-cut taken approximately 2 years after the last patient was registered.PatientsIn total, 395 patients aged >80 years at registration into EXELS were included in the analysis; of these, 42.2 % had experienced a previous thrombohaemorrhagic event.ResultsAt registration, the most frequently prescribed cytoreductive therapy for patients aged >80 years was hydroxycarbamide (HC), which accounted for 82.8 % of patients whereas anagrelide use was less frequent (8.6 %). Very elderly patients were more likely to be switched from anagrelide than from HC (47.1 vs. 17.4 %; 95 % confidence interval for difference in proportion 12.4-46.9; Chi-squared test p < 0.001). Median platelet count during treatment was ~430 × 10(9)/L. In patients aged >80 years, the main reason for switch was intolerance/side effects (34.1 %); 0/16 patients reported treatment with anagrelide was non-efficacious compared with 8/57 (14 %) patients receiving HC, and 7/16 (43.8 %) anagrelide patients switched because of intolerance versus 18/57 (31.6 %) patients receiving HC. At least one predefined clinical event (PDE) was experienced by 27.3 % of patients aged >80 years. The most common PDEs reported in the very elderly age group were death (non-PDE related; 11.1 %), other cardiovascular symptoms (5.8 %), haematological transformation (3.8 %), congestive heart failure (3.3 %), myocardial infarction and angina (2.8 %), and thromboembolic events (6.3 %).ConclusionWell-tolerated and effective cytoreductive therapy has been achieved in patients aged >80 years by following individual treatment modalities that appear in agreement with the recent European LeukemiaNet (ELN) guidelines.

Dataset Information

Cardiovascular Safety of Anagrelide Hydrochloride versus Hydroxyurea in Essential Thrombocythaemia.

Publications

Cardiovascular Safety of Anagrelide Hydrochloride versus Hydroxyurea in Essential Thrombocythaemia.

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