Table 2. Cardiac adverse events in CML patients treated with TKIs.
| CML | Study design | Method | Result | Conclusion |
|---|---|---|---|---|
| Rosti et al.60 | Retrospective; 833 patients 296 patients in late CP (LCP) and 537 patients in early CP (ECP) 400 mg or 800 mg imatinib; median FU 64 (LCP) and 18 months (ECP) | Estimation of cardiac deaths and cardiac severe adverse events (SAEs) | 77 Deaths have been recorded, 68 in the group of 296 LCP patients (22.9%) and 9 in the group of 537 ECP patients (1.6%). Three were recorded and confirmed | Overall cardiac mortality rate of 0.3% |
| Atallah et al.61 | Retrospective 1276 patients, median FU 5 years | Eligibility criteria excluded patients with cardiac problems (for example, patients with classes III and IV according to the NYHAC); routine examinations | 22 Patients (1.8%) having symptoms attributed to CHF. 18 Patients had previous medical conditions predisposing them to cardiac disease | CHF in connection with imatinib use was reasonably unambiguous in only 7 of the 1276 patients reviewed (0.5%) |
| Hatfield et al.62 | Retrospective Novartis clinical database of six trials, 2,327 patients including advanced CML (n=553), and CML in CP (n=1442), GIST (n=147), or a variety of rare malignant diseases (n=185) | Adverse events and serious adverse events were recorded by investigators in all trials | 12 Cases of CHF (0.5%) were considered as incident cases (with no previous history of CHF or left ventricular dysfunction) | Incidence of CHF is 0.2% per year across all trials |
| Gambacorti-Passerini et al.63 | Retrospective 103 patients, median age 51, median FU 48 months | Annual electrocardiogram and echocardiographic examinations | 3 Deaths non-CML-related, 2 sudden deaths. No case of CHF developed | No significant drop in mean ejection fraction values |
| Estabragh et al.64 | Prospective evaluation; 59 CML patients median FU 3.4 years | Echocardiography and MUGA scanning | No evidence of myocardial deterioration | |
| Marcolino et al.68 | Retrospective 90 CML patients for a median FU of 3.3 years | Clinical evaluation, electrocardiography, echocardiography, brain natriuretic peptide (BNP) and troponin I measurements | Mean ejection fraction 68%, Median BNP level 9.6 pg/ml. 2 Patients with either an elevated BNP or a depressed ejection fraction | Imatinib-related cardiotoxicity is an uncommon event even during long-term treatment |
| Marcolino et al.66 | Prospective; 12 CML patients | Electrocardiographic abnormalities, echocardiographic measurements and BNP levels | Median ejection fraction at baseline 67% vs 68% under FU (median intra-patient change 0.5%). Median BNP levels were 8.3 vs 7.3 pg | It is probably safe to perform cardiac monitoring on an annual basis |
| Atallah et al.67 | Retrospective 1276 patients enroled, median age 70 years Median time on imatinib 162 days | Review of all reported serious adverse events of cardiac adverse events | 22 (1.7%) were identified as having symptoms that could be attributed to systolic heart failure, 8 (0.6%) were considered possibly or probably related to imatinib | Imatinib therapy as a causal factor of CHF is uncommon |
| Ribeiro et al.65 | Prospective, 103 CML on imatinib and 57 MPN not treated with imatinib | BNP levels and echocardiographic measurements for imatinib and control groups | 4 Patients in the imatinib group presented a BNP level >100 pg/ml, one of them with depressed LVEF | No statistical difference |
Abbreviations: BNP, brain natriuretic peptide; CHF, congestive heart failure; ECP, early chronic phase; FU, follow-up; LCP, late chronic phase; MUGA, multigated acquisition scan; NYHAC, New York Heart Association Criteria.