Table 3 Summary of prospective randomised controlled trials on medical prevention of cardiac dysfunction during oncological treatment
From: Evidence-based prediction and prevention of cardiovascular morbidity in adults treated for cancer
Intervention (LOE) | Population | Study design | Primary outcome | Result |
|---|---|---|---|---|
ACEI/ARB/beta-blockers | Meta-analysis N = 2301 early breast cancer pts., HER2+/− [28] | RCT’s ACEI, ARB and/or BB | Change in LVEF | Standardized mean difference LVEF baseline vs treatment completion for all groups: − 2.36 [95% CI: − 3.23 to − 1.49] |
|  | Meta-analysis N = 633 pts. [29] | RCT’s carvedilol vs placebo | Occurrence of low LVEF | Low LVEF carvedilol vs. placebo 3.2% vs. 5.8% (OR: 0.42; 95% confidence interval: 0.18–0.99; p = 0.05). LVEF reduction carvedilol vs. placebo: mean difference 2.41% (95% CI: 0.01–4.81; p = 0.05). |
|  | Meta-analysis N = 1984 pts. [30] | RCT’s with neurohormonal therapy vs placebo (BB, ACEi, ARB, mineralocorticoid receptor antagonists) | Change in LVEF | Intervention arms had a higher LVEF on follow-up (standardized mean difference + 1.04% (95% CI 0.57–1.50) but significant heterogeneity (I2 96%) |
|  | N = 69 pts. with malignancy treated with anthracycline [29] | Prospective RCT, single-blind, enalapril vs. placebo | Change in LVEF from baseline to 6 months | Preserved LVEF in enalapril group (p = 0.58), decreased LVEF in control group (p < 0.001) |
|  | N = 40 pts. with non-Hodgkin lymphoma, combination (CHOP) chemotherapy [31] | Prospective RCT, open-label, valsartan (80 mg/day) vs. control | Explorative; changes in neurohumoral, echocardiographic, electrocardiographic markers during therapy | Compared to control, valsartan significantly inhibited the dilatation of LVDd (P = 0.01), elevation of BNP (P = 0.001), and prolongation of the QTc interval and QTc dispersion (P = 0.0009 and P = 0.02, respectively) after CHOP chemotherapy |
|  | N = 49 pts., different malignancies treated with epirubicin [32] | Prospective RCT, telmisartan vs. placebo | Change in strain rate by echocardiography compared to baseline. Biomarkers. | Decrease in strain rate in both arms, but recovery to baseline values in telmisartan group. Lower levels of inflammatory marker IL-6 in telmisartan group compared to control. No differences in (changes in) LVEF. |
|  | N = 36 acute leukemia receiving intensive chemotherapy, N = 54 hematologic malignancies receiving stem cell transplantation. LVEF ≥50% at baseline [33]. | Prospective RCT, carvedilol + enalapril vs. control group | Change in LVEF by echocardiography | Preserved LVEF in intervention arm (− 3.28 [− 5.49 to − 1.07] in control group, − 0.17 [− 2.24 to 1.90] intervention group, difference − 3.11%, p = 0.04) In control group lower incidence death/heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF < 45% (6.7% vs. 24.4%, p = 0.02). |
|  | N = 147 lymphoma pts., doxorubicin combination chemotherapy [34] | Prospective randomised three-arm trial (metoprolol, enalapril or placebo) | Clinical heart failure and subclinical cardiotoxicity | No statistically significant differences in the study arms (up to 10 yr follow-up) [35] |
|  | N = 468 early HER2+ breast cancer pts., treated with trastuzumab +/− anthracyclines [36] | Prospective randomised three-arm trial (lisinopril, carvedilol or placebo) | Cardiotoxic event | Cardiotoxicity occurred in 32% patients on placebo, 29% on carvedilol, and 30% on lisinopril. |
|  | N = 121 pts. with early breast cancer treated with adjuvant chemotherapy including anthracyclines [37] | Prospective 2 × 2 factorial placebo-controlled double-blind RCT. | Change in LVEF | The overall decline in LVEF was 2.6% (95% CI 1.5, 3.8) in the placebo group and 0.8 (95% CI − 0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. |
|  | N = 94 pts. with early HER2+ breast cancer [38] | Prospective randomised three-arm trial (perindopril, bisoprolol or placebo) | Trastuzumab-mediated left ventricular remodeling on ultrasound | No difference between groups |
Statins | N = 40 pts. with malignancy planned for anthracycline treatment [39] | Prospective RCT 6 months of atorvastatin (40 mg/day) vs. control | Rate LVEF < 50% | No difference primary endpoint (p = 0.18), but mean change in LVEF in control group significantly larger than in statin group (− 7.9 ± 8.0 vs. 1.3 ± 3.8, p < 0.001) |
Other | Meta-analysis of 2177 breast cancer pts. treated with anthracyclines +/− trastuzumab [40] | Dexrazoxane vs placebo | Rate of CHF and cardiac events | Reduction in CHF (RR: 0.19; 95% CI: 0.09 to 0.40, P < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49, p < 0.001) |
|  | N = 27 pts. treated with doxorubicin [41] | Prospective open label RCT, sildanefil (100 mg 3 times daily) vs. control | Change in mean LVEF | No difference. No difference in (changes in) serum troponin I. |