Increased Risk for Cardiovascular Events Seen in Patients With CML Taking Tyrosine Kinase Inhibitors

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Although tyrosine kinase inhibitors have dramatically increased survival for patients with chronic myeloid leukemia (CML), continuous administration of these drugs may elicit long-term toxicity, including cardiovascular adverse events. To investigate the incidence of vascular events in patients with CML treated with tyrosine kinase inhibitors, researchers analyzed data from Swedish population-based registries and found an increased risk for arterial and venous vascular events in these patients compared with the general population. The study was published in Annals of Internal Medicine by Torsten Dahlén, MD, of Karolinska University Hospital Solna, Stockholm, Sweden, and colleagues.

Although the researchers found a greater risk for myocardial infarction among those patients treated with one of the second-generation tyrosine kinase inhibitors, nilotinib (Tasigna) or dasatinib (Sprycel), compared with those taking the first-generation tyrosine kinase inhibitor imatinib, the number of events was too small to allow statistical comparison. Clinicians should consider this risk for vascular events when prescribing tyrosine kinase inhibitor therapy for their patients with CML, suggested the study authors.

Study Methodology

The researchers identified all patients who received a CML diagnosis from January 2002 to December 2012 whose names were recorded in the nationwide Swedish CML register. For each patient, five control individuals were selected randomly, matched by birth year and sex, from Sweden’s Total Population Register. They then performed record linkage with the National Patient Register to determine the occurrence of vascular events for all patients with CML and members of the control population.

A total of 896 patients with chronic-phase CML were identified in the Swedish CML Register. The mean age at diagnosis was 58 years, and 45.9% of the patients were women. The most commonly prescribed tyrosine kinase inhibitor was imatinib, which was used by 780 patients (87.1%); nilotinib was used by 241 patients (26.9%); and dasatinib was used by 210 patients (23.4%). The patients were followed for a median of 4.2 years.

The prevalence of myocardial infarction before the establishment of a CML diagnosis was 9.5% in patients ever treated with nilotinib; 7.6% in those ever treated with dasatinib; 10.9% in those treated with imatinib; and 7.8% in the control population. The control population comprised 4,438 sex- and age-matched persons without CML, corresponding to 4.95 control individuals per case.

Study Findings

There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% confidence interval [CI] = 1.1–2.1) and 2.0 (95% CI = 1.2–3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1,000 person-years, respectively) than in those receiving imatinib (8 per 1,000 person-years), although data are limited and the confidence intervals were wide and overlapped. Among 31 patients treated with a tyrosine kinase inhibitor who had a myocardial infarction, 26 (84%) had at least one major cardiac risk factor diagnosed before the event occurred.

“We observed a greater risk for both arterial and venous vascular events in patients with CML than in an age- and set-matched control population. Clinicians should be aware of these cardiovascular risk factors when initiating tyrosine kinase inhibitor therapy in patients with CML,” concluded the study authors.

The primary funding source for this study came from various health-care resources.

Dahlén T, et al: Ann Intern Med. June 14, 2016 (early release online).