Clinical Significance of Cardiac Co-Morbidities and Risk Factors for Patients Treated with Imatinib.

Imatinib is currently standard therapy for patients with success in Chronic Myeloid Leukemia (CML). Several instances of cardiac adverse events have been reported for patients while on therapy with imatinib. In many instances, these events occur in patients with pre-existing cardiac conditions. The aim of our study was to determine the occurrence of cardiac events in patients with CML treated with Imatinib, and the impact that cardiac risk factors and pre-existing cardiac conditions had on the risk of developing cardiac adverse effects.

We reviewed the medical records of 51 patients with chronic phase CML who were treated with imatinib after failing prior therapies. For each patient we collected cardiac risk factors, pre-existing cardiac disease, pre-treatment EKG and echocardiogram (ECHO) readings, as well as post-treatment changes in EKG and ECHO findings.

Pre-existing cardiac conditions were found in 14 (27%) patients, including congestive heart failure in 2 (4%), myocardial infarction in 4 (8%), atrial fibrillation in 1 (2%), benign arrhythmias in 1(2%), aortic regurgitation in 1(2%), mitral valve prolapse in 1 (2%), mitral regurgitation in 1(2%), pericarditis in 1(2%), bradycardia in1(2%) and benign arrhythmia in 1(2%). Cardiac risk factors were present in 26 patients (51%), including smoking in 10 patients (20%), hypertension in 17 (33%), diabetes mellitus in 9 (18%), obesity in 2 (4%), hyperlipidemia in 5 (10%), stress (self-reported by patient or on anxiolytic therapy) in 5 (10%), alcohol in 11 (22%), atherosclerosis in 3 (6%), and positive family history for cardiac disease in 5 patients (9.8%). Cardiac events were noted in 19 patients (37%) of whom 11 (58%) had pre-existing cardiac conditions prior to initiating imatinib treatment and 14 patients (27%) had at least one cardiac risk factor. Congestive heart failure with clinical manifestations was seen in 9 patients (18%) with documentation of decreased ejection fraction on echocardiogram seen in 3 patients (6%) who had a decrease in LVEF from a median of 55% (range 50% to 72%) to a median of 45% (range 25% to 60%). Out of the patients who developed CHF while on treatment with imitanib, 3 patients (6%) had history of cardiac conditions (atrial fibrillation in 1 (2%), congestive heart failure in 2 (4%)). Myocardial infarction was documented in 3 patients (6%), one of which had prior myocardial infarction and pacemaker, another had history of mitral valve prolapse and hypertension; one patient had hypertension, diabetes mellitus and positive family history but no prior history of heart disease. Arrhythmia was seen in 3 patients (6%). Post-treatment EKG changes occurred in 14 patients (27%) including bradycardia, PAC's, PVC's, ST-T wave changes, tachycardia and other rhythm abnormalities. These changes were usually asymptomatic. Gated cardiac study done after a median of 63 months (range 29 to 83 months) after initiation of imatinib treatment showed EF below 60% in 9 patients (18%) with a median of 55% (range 36% to 59%). None of the patients died of cardiac conditions and none discontinued imatinib therapy because of cardiac events.

Although cardiac events occur in some patients treated with imatinib, these are much more common among patients with pre-existing cardiac conditions and/or cardiac risk factors. These patients need to be monitored closely to minimize their risk and intervene early when new cardiac events arise.

Cortes:novartis: Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding. Kantarjian:novartis: Research Funding; BMS: Research Funding. O'Brien:Novartis: Research Funding.