Cardiovascular Events After Exposure to Nilotinib in Chronic Myeloid Leukemia: Long-term Follow-up.

INTRODUCTION: Nilotinib is a highly effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML). However, reports of cardiovascular toxicities caused by nilotinib have recently raised critical concerns. The aim of the present study was to evaluate the incidence of cardiovascular events (CVEs) and frequency of asymptomatic peripheral arterial disease (PAD) after long-term exposure to nilotinib.

PATIENTS AND METHODS: In the present retrospective cohort, we evaluated the incidence of CVEs in 63 CML patients treated with nilotinib. The results of Doppler ultrasound examination of the carotid and vertebral and lower extremity arteries with ankle-brachial index measurements were collected in asymptomatic patients. The clinical outcome was a composite endpoint of PAD, acute coronary events, stroke, heart failure, and cardiovascular death.

RESULTS: Sixty-three patients with a median age of 60 years were followed up for a median duration of 63 months. After a median nilotinib exposure of 49.30 months (range, 7.00-117.95 months), for a total exposure of 178.7 patient-years, 6 patients (9%) had experienced the clinical outcome. Four patients (8%) had abnormal arterial leg Doppler ultrasound findings. No significant lesions were reported in carotid/vertebral artery ultrasound examinations. Together, hypertension and low-density lipoprotein cholesterol > 2 mmol/L significantly increased the risk of CVEs or abnormal ultrasound findings (odds ratio, 37.65; 95% confidence interval, 4.06-348.9).

CONCLUSION: The incidence of CVEs and the frequency of asymptomatic PAD in this population was low, and CVEs were associated with cardiovascular risk factors. Aggressive risk factor modification and applying standard definitions for measuring cardiovascular outcomes might have contributed to the findings. Further prospective and adequately powered studies are needed to explore the effect of the cardiovascular risk profile on CVEs in CML patients taking nilotinib.