Table 1.
Characteristics of the included trials.
| Study ID | Sample size (EG/CG) |
Median age | Types of cancer | Patients and detailed chemotherapy or radiotherapy | Intervention | Baseline LVEF | Follow-up duration | Outcomes | ||
|---|---|---|---|---|---|---|---|---|---|---|
| EG | CG | EG | CG | |||||||
| Silber et al., 2004 | 69/66 | EG: 17.8 ± 5.60 CG: 18.9 ± 6.17 |
Long-term survivors of pediatric cancers | The target population consisted of patients aged 8 years and older who developed cancer before the age of 20 years and had been treated with anthracyclines. | Enalapril | Placebo | NR | NR | Mean follow-up duration of 34.6 months | The rate of change in the MCI and LVESWS, stress-velocity index, left ventricular shortening fraction, adverse events, functional status, and quality of life |
| Cardinale et al., 2006 | 56/58 | 45 ± 12 | Breast cancer, acute myeloid leukemia, etc. | High-dose chemotherapy including carmustine, etoposide, cytarabine, melphalan, daunorubicin, carboplatin, idarubicin, mitoxantrone, epirubicin, etc. | Enalapril | None | NR | NR | 12 months | The occurrence of cardiotoxicity, efficacy of enalapril on LVEF, and adverse cardiac events |
| Georgakopoulos et al., 2010 | 43/40 | EG: 47.4 ± 16.2 CG: 49.1 ± 19.4 |
Lymphoma | The CT regimen consisted of 6–8 cycles of the “ABVD schema” for HL as follows: doxorubicin (25 mg/m2), bleomycin (10 mg/m2), vinblastine (6 mg/m2), and dacarbazine (375 mg/m2) intravenously on day 1 and day 15 every 4 weeks. The NHL patients received the “R-CHOP schema” as follows: rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2) intravenously on day 1 and prednisolone (100 mg/m2) orally on days 1–5 every 3 weeks. |
Enalapril | None | 65.2 ± 7.1 | 67.6 ± 7.1 | 36 months | Echocardiographic evaluations |
| Bosch et al., 2013 | 45/45 | 50 ± 13 | Acute leukemia, relapsed or refractory; Hodgkin’s and non-Hodgkin’s lymphoma; and multiple myeloma |
NR | Enalapril and carvedilol | None | NR | NR | 6 months | Global LVEF, TnI and BNP levels, incidence of death, heart failure or significant LVSD, diastolic function, and incidence of severe life-threatening adverse events |
| Janbabai et al., 2017 | 34/35 | EG: 47.76 ± 11.81 CG: 47.06 ± 12.39 |
Breast cancer (60 patients), Hodgkin’s lymphoma (six patients), Wilms tumor (one patient), lung cancer (one patient) and bone sarcoma (one patient) | Sixty patients had breast cancer and received doxorubicin and cyclophosphamide; six patients had Hodgkin’s lymphoma and underwent R-CHOP chemotherapy, which included rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; one patient had a Wilms tumor and received vincristine, dactinomycin, doxorubicin, cyclophosphamide, and etoposide; one patient had lung cancer and received vincristine, doxorubicin, and cyclophosphamide; and one patient had bone sarcoma and received cisplatin and doxorubicin. All patients received doxorubicin, and most patients received cyclophosphamide. None of the patients received trastuzumab or radiotherapy during the 6-month follow-up period. | Enalapril | Placebo | 59.39 ± 6.95 | 59.61 ± 5.70 | 6 months | Changes from baseline in LVEF, troponin I and CK-MB levels and the incidences of death, HF, significant LV systolic dysfunction, diastolic dysfunction, and severe life-threatening adverse events |
| Cardinale et al., 2018 | 136/137 | 51 ± 12 | Breast cancer; acute leukemia, non-Hodgkin’s lymphoma; Hodgkin’s lymphoma; lymphoma, unspecified type; sarcoma; etc. | The median number of cycles of anthracyclines was four cycles delivered over 65 days. Epirubicin and doxorubicin were the most commonly prescribed anthracyclines with a median cumulative dose of 360 and 240 mg/m2, respectively. In total, 63% of the patients with breast cancer were treated with taxanes, and 22.5% of the patients were treated with trastuzumab. In total, two patients were treated with a tyrosine-kinase inhibitor, imatinib. | Enalapril in all patients was started before chemotherapy | Enalapril started only in patients with an increase in troponin during or after chemotherapy | 63.5 ± 5.9 | 63.9 ± 6.1 | 12 months | An incidence of troponin elevation above the threshold, LVEF <50% and >10% LVEF reduction, death from cardiovascular causes, death from any cause, hospitalization for cardiovascular causes, and major adverse cardiovascular events |
| Gupta et al., 2018 | 44/40 | EG: 8.85 ± 3.15 CG: 8.77 ± 2.86 |
Acute lymphoblastic leukemia/lymphoma | Projected cumulative anthracycline dose was ≥200 mg/m2. | Enalapril | Placebo | 65.73 ± 5.41 | 64.85 ± 4.94 | 6 months | LVEF, changes in cardiac biomarkers, and the development of heart failure or arrhythmias |
CG, control group; CK-MB, creatinine kinase-MB; EG, experimental group; NR, not reported; FS, fractional shortening; LVESWS, left ventricular end-systolic wall stress; MCI, maximum cardiac index; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; HF, heart failure; LA, left atrium; LVEDD, left ventricular end-diastolic dimension; LVEDS, left ventricular end-systolic dimension; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVSD, left ventricular systolic dysfunction.