Effects of the Angiotensin II Receptor Blocker (Candesartan) on Anthracycline-induced Cardiotoxicity

Anthracycline-induced cardiotoxicity can result in acute, sub-acute and chronic complications, which can lead to cardiomyopathy and heart failure. The mortality and morbidity are increased in patients who have anthracycline- induced cardiotoxicity. A few previous studies have demonstrated the efficacy of some agents in preventing cardiotoxicity from anthracycline. Objectives: To assess the efficacy of an angiotensin II receptor blocker (candesartan), in preventing anthracycline-induced cardiotoxicity, and to evaluate the side effects of candesartan in cancer-patients who received doxorubicin. Methods: Consecutive patients who were scheduled for treatment with doxorubicin from March 1, 2009 to January 31, 2010 were recruited. Breast cancer or lymphoma patients, who had definite coronary artery disease (CAD), left ventricular (LV) dysfunction; chronic kidney disease (CKD) and hyperkalemia were excluded. Patients were randomized into two groups; the first group received candesartan 4-32 mg daily while the second group did not (controls group) until the end of the anthracycline regimen. Baseline echocardiographic parameters were measured and followed up after 3 courses of anthracycline administration. The changing of echocardiographic parameters, serum potassium levels and serum creatinine levels were recorded and analyzed. Results: There were 21 patients enrolled. The mean age of the candesartan group was 51.1 ± 11.31years, and 54.20 ± 10.21 years for the control group (p=0.528). No significant changes were observed in blood pressure and heart rate between the two groups. There were significant increases in potassium and creatinine levels in the candesartan group (p= 0.001 and 0.001, respectively). There was a significant difference in left ventricular ejection fraction (LVEF) at the end of the study between the candesartan and control group (67.10 ± 6.12% and 62.60 ± 7.75% respectively, p= 0.023). There was a significant decrease in LVEF (69.00 ± 8.82% and 62.60 ± 7.75%, p=0.03) from the baseline to the half course of chemotherapy in the control group. There was no significant change in LVEF observed in the candesartan group. Conclusion: These results indicate that candesartan may have a potential in preventing the anthracycline-induced cardiotoxicity in cancer patients. It increases serum potassium levels and creatinine levels but does not induce hyperkalemia or acute kidney injury. Future long-term and larger population studies are necessary. Keywords: anthracycline, cardiotoxicity, angiotensin II receptor blocker (candesartan), prevention