Ramipril and bisoprolol significantly reduced subclinical cardiac damage at 24 months compared to placebo (11.4% vs 39.3% for ramipril, P<0.001; 9.6% vs 43.5% for bisoprolol, P<0.001).
RCT (n=262)
Double-blind
2 × 2 factorial
Yes
Do ramipril and/or bisoprolol prevent subclinical cardiac damage in patients with nonmetastatic breast cancer undergoing anthracycline-based chemotherapy?
Ramipril and bisoprolol, alone or in combination, significantly reduce the incidence of subclinical cardiac damage in patients with nonmetastatic breast cancer undergoing anthracycline-based chemotherapy.
Absolute Event Rate: 11.4% vs 39.3%
p-value: p=<0.001
BACKGROUND: Anthracycline-based chemotherapy is a cornerstone in breast cancer treatment but is associated with cardiotoxicity, including subclinical cardiac damage. This study evaluates the efficacy of ramipril and bisoprolol in preventing subclinical cardiac impairment in patients with nonmetastatic breast cancer undergoing anthracycline-based chemotherapy. PATIENTS AND METHODS: The SAFE trial is a multicenter, 2 × 2 factorial, randomized, placebo-controlled, double-blind study involving 262 patients. Participants were allocated to one of four groups: placebo-placebo, ramipril-placebo, bisoprolol-placebo, or ramipril-bisoprolol, administered concurrently with chemotherapy. Subclinical cardiac damage was assessed at 24 months using echocardiographic measures, specifically a ≥10% reduction in three-dimensional left ventricular ejection fraction (3D-LVEF) or global longitudinal strain (GLS). RESULTS: At 24 months, patients receiving ramipril, bisoprolol, or their combination experienced significantly smaller declines in 3D-LVEF compared with placebo (-2.1%, -2.2%, and -3.4%, respectively; all P < 0.001). GLS results were consistent with these findings (P < 0.001). Subclinical cardiac damage occurred in 11.4% of patients receiving ramipril versus 39.3% without ramipril (P < 0.001), and in 9.6% of patients receiving bisoprolol versus 43.5% without bisoprolol (P < 0.001). CONCLUSIONS: Ramipril and bisoprolol significantly reduce the incidence of subclinical cardiac damage in patients with breast cancer undergoing anthracycline-based chemotherapy, thus supporting their use as early prevention cardioprotective strategies.
Meattini et al. (2025) conducted an RCT in Nonmetastatic breast cancer undergoing anthracycline-based chemotherapy (n=262). Ramipril and bisoprolol vs. Placebo was evaluated on Subclinical cardiac damage (≥10% reduction in 3D-LVEF or global longitudinal strain) (p=<0.001). Ramipril and bisoprolol significantly reduced subclinical cardiac damage at 24 months compared to placebo (11.4% vs 39.3% for ramipril, P<0.001; 9.6% vs 43.5% for bisoprolol, P<0.001).