Adjunctive pharmacologic strategies for the prevention of chemotherapy-induced cardiotoxicity
| Study . | Year . | Cohort (n) . | Follow-up time . | Cardiotoxic chemotherapy . | Radiation therapy . | Preventive therapy . | Cardiotoxicity definition . | Event rate with vs without previous therapy . |
|---|---|---|---|---|---|---|---|---|
| Beta-blocker | ||||||||
| Kalay et al78 | 2006 | Breast cancer (68%), lymphoma (18%) | 6 mo | Anthracyclines: doxorubicin 520 mg/m2 or epirubicin 780 mg/m2 | 0% | Carvedilol 12.5 mg per day, started before CT and continued for 6 mo | LVEF baseline to 6 mo | Carvedilol: 70.5% to 69.7% Control: 68.9% to 52.3%* |
| Georgakopoulos et al79 | 2010 | HL and NHL (n = 125) | 12 mo | ABVD R-CHOP | 21% | Metoprolol 25-50 mg/BID or Enalapril 2.5-10 mg/BID started with CT and continued | LVEF baseline to 12 mo | Metoprolol: 65.7% to 63.3% Enalapril: 65.2% to 63.9% Control: 67.6% to 66.6% |
| Jhorawat et al80 | 2014 | NHL (n = 44), HL (n = 9), ALL (n = 1) | 6 mo | Doxorubicin 428 and 395 mg/m2 in control and intervention gorup | NA | Carvedilol 12.5 mg per day, started before CT and continued for 6 mo | LVEF baseline to 6 mo Incidence of LVEF decrease >10% from baseline | Carvedilol: 63.2% to 63.9% Control: 67.6% to 60.8%* Carvedilol vs placebo: 14.3% vs 40.9%* |
| Abuosa et al81 | 2018 | Breast (n = 72), NHL (n = 95), other (n = 46) | 6 mo | Doxorubicin 252-282 mg/m2 | NA | Carvedilol 6.25 mg, 12.5 mg, or 25 mg per day, started prophylactically and continued for 6 mo | LVEF baseline to 6 mo Incidence of LVEF decrease to 50% | 62% to 58.2% w/placebo, 61.4% to 60% w/6.25 mg carvedilol, 60% to 58% w/12.5 mg carvedilol, 60.4% to 59.2% w/25 mg carvedilol Carvedilol 12.5 mg vs control 1% vs 11%* |
| ACE inhibitor/ARB | ||||||||
| Nakamae et al82 | 2005 | NHL (n = 40) | Day 3 after initiation | CHOP | 0% | Valsartan 80 mg/d started and continued with CT | LVEDD BNP QTc | 45 vs 49 mm* 30 vs 80 pg/dL* 420 vs 435 ms* |
| Cardinale et al83 | 2006 | HDC (n = 114, 60% NHL and breast cancer) + cTnI > ULN within 3 d of any cycle | 12 mo | Various, cumulative doxorubicin equivalent dose 335 mg/m2 | 11% | Enalapril 2-20 mg per day, started after cTnI elevation and continued in f/u | LVEF decline >10% to <50% HF Arrhythmias | 0% vs 43%* 0% vs 24%* 2% vs 17%* |
| Dessi et al84 | 2011 | Various (n = 49, breast cancer 37%) | 12 mo | Epirubicin 400 mg/m2 | 0% | Telmisartan 40 mg/d, 1 wk before, 6 mo after CT | Strain rate | 1.75 vs 1.5* |
| Beta-blocker ACE inhibitor combination | ||||||||
| Bosch et al. (OVERCOME trial)85 | 2013 | Acute leukemia (n = 36) or HSCT (n = 54) | 6 mo | Anthracyclines (40% before, 40% during, cumulative 265 mg/m2) | 18% | Carvedilol (6.25- 25 mg BID) and Enalapril (2.5-10 mg BID), started 24 h before CT and continued in f/u | LVEF by TTE LVEF by CMR | −0.17 vs −3.28* 0.36 vs −3.04 |
| Statin | ||||||||
| Acar et al86 | 2011 | Various (n = 40) NHL, 60%) | 6 mo | Anthracyclines: doxorubicin 256 mg/m2, idarubicin 297 mg/m2 | NA | Atorvastatin 40 mg per day, started before and continued for 6 mo after CT | LVEF LVEDD LVESD | 1.3 vs −7.9* −0.15 vs 2.0* −1.35 vs 2.1* |
| Study . | Year . | Cohort (n) . | Follow-up time . | Cardiotoxic chemotherapy . | Radiation therapy . | Preventive therapy . | Cardiotoxicity definition . | Event rate with vs without previous therapy . |
|---|---|---|---|---|---|---|---|---|
| Beta-blocker | ||||||||
| Kalay et al78 | 2006 | Breast cancer (68%), lymphoma (18%) | 6 mo | Anthracyclines: doxorubicin 520 mg/m2 or epirubicin 780 mg/m2 | 0% | Carvedilol 12.5 mg per day, started before CT and continued for 6 mo | LVEF baseline to 6 mo | Carvedilol: 70.5% to 69.7% Control: 68.9% to 52.3%* |
| Georgakopoulos et al79 | 2010 | HL and NHL (n = 125) | 12 mo | ABVD R-CHOP | 21% | Metoprolol 25-50 mg/BID or Enalapril 2.5-10 mg/BID started with CT and continued | LVEF baseline to 12 mo | Metoprolol: 65.7% to 63.3% Enalapril: 65.2% to 63.9% Control: 67.6% to 66.6% |
| Jhorawat et al80 | 2014 | NHL (n = 44), HL (n = 9), ALL (n = 1) | 6 mo | Doxorubicin 428 and 395 mg/m2 in control and intervention gorup | NA | Carvedilol 12.5 mg per day, started before CT and continued for 6 mo | LVEF baseline to 6 mo Incidence of LVEF decrease >10% from baseline | Carvedilol: 63.2% to 63.9% Control: 67.6% to 60.8%* Carvedilol vs placebo: 14.3% vs 40.9%* |
| Abuosa et al81 | 2018 | Breast (n = 72), NHL (n = 95), other (n = 46) | 6 mo | Doxorubicin 252-282 mg/m2 | NA | Carvedilol 6.25 mg, 12.5 mg, or 25 mg per day, started prophylactically and continued for 6 mo | LVEF baseline to 6 mo Incidence of LVEF decrease to 50% | 62% to 58.2% w/placebo, 61.4% to 60% w/6.25 mg carvedilol, 60% to 58% w/12.5 mg carvedilol, 60.4% to 59.2% w/25 mg carvedilol Carvedilol 12.5 mg vs control 1% vs 11%* |
| ACE inhibitor/ARB | ||||||||
| Nakamae et al82 | 2005 | NHL (n = 40) | Day 3 after initiation | CHOP | 0% | Valsartan 80 mg/d started and continued with CT | LVEDD BNP QTc | 45 vs 49 mm* 30 vs 80 pg/dL* 420 vs 435 ms* |
| Cardinale et al83 | 2006 | HDC (n = 114, 60% NHL and breast cancer) + cTnI > ULN within 3 d of any cycle | 12 mo | Various, cumulative doxorubicin equivalent dose 335 mg/m2 | 11% | Enalapril 2-20 mg per day, started after cTnI elevation and continued in f/u | LVEF decline >10% to <50% HF Arrhythmias | 0% vs 43%* 0% vs 24%* 2% vs 17%* |
| Dessi et al84 | 2011 | Various (n = 49, breast cancer 37%) | 12 mo | Epirubicin 400 mg/m2 | 0% | Telmisartan 40 mg/d, 1 wk before, 6 mo after CT | Strain rate | 1.75 vs 1.5* |
| Beta-blocker ACE inhibitor combination | ||||||||
| Bosch et al. (OVERCOME trial)85 | 2013 | Acute leukemia (n = 36) or HSCT (n = 54) | 6 mo | Anthracyclines (40% before, 40% during, cumulative 265 mg/m2) | 18% | Carvedilol (6.25- 25 mg BID) and Enalapril (2.5-10 mg BID), started 24 h before CT and continued in f/u | LVEF by TTE LVEF by CMR | −0.17 vs −3.28* 0.36 vs −3.04 |
| Statin | ||||||||
| Acar et al86 | 2011 | Various (n = 40) NHL, 60%) | 6 mo | Anthracyclines: doxorubicin 256 mg/m2, idarubicin 297 mg/m2 | NA | Atorvastatin 40 mg per day, started before and continued for 6 mo after CT | LVEF LVEDD LVESD | 1.3 vs −7.9* −0.15 vs 2.0* −1.35 vs 2.1* |
ABVD, Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine; ALL, acute lymphocytic leukemia; BB, beta-blocker; BID, twice a day; CMR, cardiac magnetic resonance imaging; CT, chemotherapy; cTnI, cardiac troponin I; F/u, follow-up; FS, fractional shortening; HF, heart failure; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; LVESWS, left ventricular end-systolic wall stress; NS, nonsignificant; NT-pro-BNP, N-terminal-probrain natriuretic peptide; QTc, corrected QT interval; TTE, transthoracic echocardiogram; ULN, upper limit of normal.
P < .05.