Author: By Shreeya Nanda, Senior medwireNews Reporter
medwireNews: The use of cardioprotective therapies such as bisoprolol and ramipril could help to prevent subclinical cardiac damage in nonmetastatic breast cancer patients receiving anthracycline-based chemotherapy, suggest phase 3 trial data.
Reporting on a preplanned interim analysis, Icro Meattini, from the University of Florence in Italy, and co-investigators say that the cardioprotective agents “are overall well tolerated and seem to protect against LVEF [left ventricular ejection fraction] decline and heart remodelling” in this patient population.
“Nevertheless, these encouraging preliminary results will have to be confirmed at the final results analysis”, they write in JAMA Oncology.
In the double-blind SAFE trial, participants were randomly assigned to receive the beta blocker bisoprolol or the ACE inhibitor ramipril, either as single agents or together, or placebo for a year from the start of chemotherapy or until the end of trastuzumab therapy for those receiving concomitant treatment with the HER2-targeted agent. The doses of bisoprolol and ramipril were systematically up-titrated to the daily target dose of 5 mg if tolerated.
The interim analysis included 174 participants, aged a median of 48 years, who had completed treatment and undergone cardiac assessment at the 12-month follow-up. The majority had stage I–II disease (82.2%) and were hormone receptor-positive (75.9%).
At the 12-month assessment, LVEF as assessed by three-dimensional echocardiography worsened to a significantly lesser degree from baseline in patients who received cardioprotective agents than those given placebo, by a respective 1.9%, 3.0% and 1.3% in the bisoprolol, ramipril and combination arms versus 4.4% in the placebo arm.
And the proportion of participants with an LVEF reduction of at least 10% was significantly lower in the bisoprolol, ramipril and combination groups than the placebo group, at 11.4%, 11.5% and 6.8% versus 19.0%, respectively.
The cardioprotective agents exerted a similarly beneficial effect on global longitudinal strain (GLS), which worsened from baseline by 0.6% in the bisoprolol arm, 1.5% in the ramipril arm, and 6.0% in the placebo arm, but improved by 0.1% in the combination arm.
The proportion of patients with a GLS worsening of 10% or greater was 13.6%, 15.9%, 13.6% and 35.7% among those given bisoprolol, ramipril, the combination and placebo, respectively. The differences between the active treatment and placebo groups were significant for both GLS outcomes.
Icro Meattini and colleagues highlight that there was a significant benefit for almost all subgroups in terms of changes in LVEF and GLS with the use of bisoprolol, but there was no significant impact of ramipril on LVEF change in any subgroup.
They add that “[c]ompliance with the study drugs was good overall”, but note that a significantly lower proportion of combination-treated participants up-titrated to the maximum dose of the study drugs than those given bisoprolol, ramipril or placebo, at 79.1% versus 95.4%, 97.7% and 90.4%, respectively.
And the incidence of dose reduction or discontinuation due to hypotension was significantly higher in the combination than the bisoprolol, ramipril or placebo groups (14.0 vs 2.3, 0.0 and 7.2%, respectively); this was also the case for cough (4.7 vs 0.0, 2.3 and 0.0%, respectively).
Reference
Livi L, Barletta G, Martella F, et al. Cardioprotective strategy for patients with nonmetastatic breast cancer who are receiving an anthracycline-based chemotherapy. A randomized clinical trial. JAMA Oncol; Advance online publication 26 August 2021. doi: 10.1001/jamaoncol.2021.3395
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