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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
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Major clinical trials for primary prevention of anthracycline-induced cardiotoxicity

Major clinical trials for primary prevention of anthracycline-induced cardiotoxicity
Citation Study design Type(s) of malignancy Major findings
Beta blockers
Kalay 2006[1]
  • Randomized
  • Single-blind
  • Placebo-controlled
  • Carvedilol 12.5 mg daily (n = 25)
  • Placebo (n = 25)
  • All
  • Fewer deaths among those receiving carvedilol than placebo (one versus four, respectively).
  • Those receiving carvedilol did not experience a significant decline in LVEF (70.5 to 69.7%, p = 0.3), while those receiving placebo did (68.9 to 52.3%, p = 0.001).
Kaya 2013[2]
  • Randomized
  • Double-blind
  • Placebo-controlled
  • Nebivolol 5 mg daily (n = 27)
  • Placebo (n = 18)
  • Breast cancer
  • Those receiving nebivolol did not experience significant worsening of echocardiographic parameters at six months while those receiving placebo did:
    • Mean LVEF (%):
      • Nebivolol: 65.6 → 63.8
      • Placebo: 66.6 → 57.5
    • Mean LVEDD (mm):
      • Nebivolol: 47.0 → 47.1, p = 0.93
      • Placebo: 47.2 → 52.0, p = 0.01
    • Mean LVESD (mm):
      • Nebivolol: 30.4 → 31.0, p = 0.20
      • Placebo: 29.7 → 33.4, p = 0.01
    • Mean NT-proBNP (pmol/L):
      • Nebivolol: 147 → 152, p = 0.77
      • Placebo: 144 → 204, p = 0.01
Georgakopoulos 2010[3]
  • Randomized
  • Metoprolol (formulation not specified) (n = 42)
  • Enalapril (n = 43)
  • No additional treatment (n = 40)
  • Lymphoma
  • No difference in heart failure, LVEF, LVEDD, LVESD, or other echocardiographic parameters with metoprolol versus placebo.
Gulati 2016[4]
  • Randomized
  • Placebo-controlled
  • Double-blind
  • 2 × 2 factorial
  • n = 130
  • Metoprolol succinate (target dose 100 mg daily) (n = 58)
  • Candesartan (target dose 325 mg daily) (n = 60)
  • Breast cancer
  • No significant effect on change in LVEF with metoprolol versus placebo (preliminary results).
Angiotensin inhibitors (ACEIs/ARBs)
Georgakopoulos 2010[3]
  • Randomized
  • Metoprolol (n = 42)
  • Enalapril (n = 43)
  • No additional treatment (n = 40)
  • Lymphoma
  • No difference in heart failure, LVEF, LVEDD, LVESD, or other echocardiographic parameters with enalapril versus placebo.
Gulati 2016[4]
  • Randomized
  • Placebo-controlled
  • Double-blind
  • 2 × 2 factorial
  • n = 130
  • Metoprolol succinate (target dose 100 mg daily) (n = 58)
  • Candesartan (target dose 325 mg daily) (n = 60)
  • Breast cancer
  • Those receiving candesartan did not experience a decline in LVEF (0.8, CI –0.4 to 1.9) while those receiving placebo did (2.6, CI 1.5-3.8, p = 0.026) (preliminary results of intention-to-treat analysis).
Combined beta blockade and angiotensin inhibition
Bosch 2013[5]
  • Randomized
  • Enalapril (target dose 10 mg twice daily) and carvedilol (target dose 25 mg twice daily) (n = 45)
  • No additional treatment (n = 45)
  • Hematologic malignancies
  • Those receiving candesartan did not experience a decline in LVEF while those receiving placebo did (3.1% decrease, p = 0.035).
  • Incidence of death or heart failure was lower in the enalapril/carvedilol arm compared with those receiving placebo (6.7 versus 22%, p = 0.036).
Dexrazoxane
van Dalen 2011[6]
  • Meta-analysis (10 randomized controlled trials)
  • Dexrazoxane (n = 799)
  • Placebo (n = 285)
  • No additional treatment (n = 535)
  • Breast cancer
  • Leukemia
  • Other
  • Risk of clinical heart failure was lower with dexrazoxane versus placebo (RR 0.18, CI 0.1-0.32, p<0.001).
  • No effect on overall survival.
Statins
Acar 2011[7]
  • Randomized
  • Atorvastatin 40 mg daily (n = 20)
  • No additional treatment (n = 20)
  • Hematologic malignancies
  • Those receiving atorvastatin did not experience worsening echocardiographic parameters while those receiving placebo did:
    • Mean LVEF (%):
      • Atorvastatin: 61.3 → 62.6
      • Control: 62.9 → 55.0
      • p value for comparison of mean change <0.001
    • Mean LVEDD (mm):
      • Atorvastatin: 46.5 → 46.3
      • Control: 47.2 → 49.2
      • p value for comparison of mean change = 0.021
    • Mean LVESD (mm):
      • Atorvastatin: 30.9 → 29.6
      • Control: 30.3 → 32.3
      • p value for comparison of mean change <0.001
Seicean 2012[8]
  • Retrospective
  • Observational
  • Statin prescribed for other indication (n = 67)
  • Propensity-matched controls (n = 134)
  • Breast cancer
  • Risk of heart failure hospitalization was lower for those receiving a statin than those receiving placebo (HR 0.3, CI 0.1-0.9, p<0.03).
LVEF: left ventricular ejection fraction; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricular end-systolic diameter; NT-proBNP: N-terminal pro B-type natriuretic peptide; ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CI: confidence interval; RR: relative risk; HR: hazard ratio.
References:
  1. Kalay N, Basar E, Ozdogru I, et al. Protective Effects of Carvedilol Against Anthracycline-Induced Cardiomyopathy. J Am Coll Cardiol 2006; 48:2258.
  2. Kaya MG, Ozkan M, Gunebakmaz O, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol 2013; 167:2306.
  3. Georgakopoulos P, Roussou P, Matsakas E, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol 2010; 85:894.
  4. Gulati G, Heck SL, Ree AH, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J 2016; 37:1671.
  5. Bosch X, Rovira M, Sitges M, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol 2013; 61:2355.
  6. van Dalen EC, Caron HN, Dickinson HO, and Kremer LC. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev 2011; :CD003917.
  7. Acar Z, Kale A, Turgut M, et al. Efficiency of atorvastatin in the protection of anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2011; 58:988.
  8. Seicean S, Seicean A, Plana JC, et al. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol 2012; 60:2384.
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