Table 2.
Trials of primary prevention strategies for cardiotoxicity in patients with breast cancer
| Study | Population | Interventions | Cardiotoxicity Outcome | Findings |
|---|---|---|---|---|
| PRADA [55] | 130 patients treated with FEC 22% received trastuzumab |
Candesartan Metoprolol XL Candesartan + metoprolol XL Placebo |
Change in LVEF by cardiac MRI | Decline in LVEF from baseline to end of study was lower in the candesartan group (−0.8%) compared with the placebo group (−2.6%). LVEF decline in the metoprolol group (−1.6%) was not significantly different compared with placebo. |
| MANTICORE [58■] | 94 patients treated with adjuvant chemotherapy (FEC 22%, TC 77%, ACT 1%) plus trastuzumab | Perindopril Bisoprolol Placebo |
Change in LVEDVi by cardiac MRI | No difference in change in LVEDVi from baseline to end of study in the perindopril or bisoprolol groups compared with placebo (+7 ml/m2 versus + 8 ml/m2 versus +4 ml/m2, P = 0.36). Small reduction in LVEF decline with bisoprolol but not perindopril compared with placebo (−1 versus −3 versus −5%, P = 0.001) |
| Boekhout et al. [56■] | 206 patients treated with anthracyclines plus trastuzumab | Candesartan Placebo |
↓ LVEF ≥ 15% from baseline or to <45% | No difference in rate of cardiotoxicity between candesartan group versus placebo (19 versus 16%, P = 0.58) NT-proBNP and hs-TnT were not associated with changes in LVEF. Candesartan did not affect changes in biomarkers. |
| Guglin et al. [59] | 468 patients treated with adjuvant chemotherapy plus trastuzumab 39% with prior exposureto anthracycline-based chemotherapy |
Lisinopril Carvedilol ER Placebo |
↓ LVEF ≥10% or ≥5 to <50% | No difference in rate of cardiotoxicity between lisinopril group or carvedilol group versus placebo (30 versus 29 versus 32%, P = ns). In the subset of patients treated with anthracyclines, the rate of cardiotoxicity was lower in the lisinopril and carvedilol groups versus placebo (37 versus 31 versus 47%, P = 0.009) |
ACT, doxorubicin, cyclophosphamide, docetaxel; FEC, 5-fluorouracil, epirubicin, and cyclophosphamide; LVEDVi, left ventricular end diastolic volume index; TC, docetaxel, carboplatin.