Some of you may remember last year a scientific journal raising concerns about possible cardiac effects of Glivec - in particular the potential for casuing congestive cardiac failure.
You may be interested in the following information:
Incidence of Congestive Heart Failure in Patients Receiving Imatinib Treatment
Allen Yang, MD, PhD:
Recently, it has been reported that imatinib use can lead to congestive heart failure in the setting of chronic-phase CML. In a retrospective review of 1276 patients with CML who were treated with imatinib at the M.D. Anderson Cancer Center in Houston, Texas, the investigators found that the incidence of congestive heart failure was quite low (Capsule Summary).[3]
Moshe Talpaz, MD:
This retrospective study is timely and important because of the recent publication in Nature Medicine reporting that long?term administration of imatinib is associated with cardiac toxicity.[4] In this larger retrospective review presented by Atallah and colleagues, only 22 out of 1276 patients (1.8%) developed some degree of cardiac toxicity. In further analysis, most of these patients were found to have preexisting hypertension or coronary disease. Furthermore, patients who developed congestive heart failure tended to be older with a median age of 70 years (range: 49-83). That being said, congestive heart failure is generally more prevalent in older people, particularly those older than 70 years of age.
These findings suggest that only a tiny fraction of patients develop imatinib?associated cardiac toxicity, which may be reversible. I treated a patient who developed cardiac toxicity, which was rapidly reversible upon cessation of imatinib. The potential for cardiac toxicity should not be ignored in patients on imatinib, but it appears to be a problem of small magnitude.
Charles L. Sawyers, MD:
These data, in addition to data presented by Dr. Druker in his recent paper published in The New England Journal of Medicine,[2] suggest that the problem of congestive heart failure and cardiotoxicity has probably been overstated, although it cannot be ignored. In my practice, I have not instituted cardiac prescreening in patients about to start treatment with imatinib. I have not felt this was critical, and these new data do not compel me to change my approach.
Brian Druker, MD:
I agree with the comments of the panel. When the Nature Medicine article was first published, most of us who treat patients with CML were surprised because we did not see this in our own practices. Now that more data are emerging, we can say with confidence that cardiac adverse effects are rare and that patients with cardiac toxicity often have risk factors such as older age, high blood pressure, diabetes, or coronary artery disease. In our clinic, we have instituted screening for patients with predisposing risk factors. We also wanted to assess whether we were missing mild heart failure cases, so we prospectively screened approximately 50 patients using blood sampling and echocardiography. Employing this approach, we have not found even mild degrees of congestive heart failure related to imatinib use (B. Druker, MD, unpublished data, 2006). Based on these data, we now can say with relative confidence that we do not need to perform routine cardiac screening in all patients who are candidates for imatinib. However, we would err on the side of caution and monitor patients with preexisting cardiac risk factors.
Allen Yang, MD, PhD:
Would there ever be a patient with CML whose cardiac history would suggest that you not recommend imatinib? If so, what alternative treatments would you recommend?
Brian Druker, MD:
If one takes the Nature Medicine article at face value, there was some suggestion that the inhibition of ABL kinase was responsible for the cardiac adverse effects. Thus, any ABL kinase inhibitor might have potential cardiac toxicity. For a patient with a history of heart failure, very careful monitoring would be required We would institute or increase diuretics, and add or adjust other cardiac medications, in consultation with a cardiologist in managing such patients. Additionally, I would not treat a patient with a history of heart failure with an imatinib dose higher than 400 mg, because fluid retention is dose related.
It seems that the original journal article was NOT entirely accurate