medwireNews: Cardioprotective pharmacologic therapy may be effective against anthracycline-related subclinical heart damage in women with nonmetastatic breast cancer, with bisoprolol potentially offering greater benefits than ramipril, interim SAFE study data suggest.
The multicenter, phase 3 trial included 262 women with no history of cardiovascular disease who were undergoing primary or postoperative systemic therapy using an anthracycline-based regimen. The majority (82.2%) had stage I or II breast cancer and were hormone receptor-positive (75.9%).
The women were randomly assigned to treatment with either the beta blocker bisoprolol, the ACE inhibitor ramipril, bisoprolol plus ramipril, or placebo. Doses for all groups were up-titrated on a weekly basis to the daily target of 5 mg for each group, but the researchers note that significantly fewer individuals in the bisoprolol plus ramipril group tolerated the full dose (79.1%) than in the bisoprolol (95.4%) and ramipril (97.7%) monotherapy groups.
At the time of the interim analysis, 174 women (median age 48 years) had completed their 12-month cardiologic assessment and reached the end of treatment.
Icro Meattini (University of Florence, Italy) and co-investigators report that those who received placebo (n=42) experienced a mean 4.4% reduction in 3-dimensional (3D) echocardiography–left ventricular ejection fraction (LVEF) from baseline to 12 months.
By comparison, the reductions in the bisoprolol (n=45), ramipril (n=44), and bisoprolol plus ramipril (n=43) arms were 1.9%, 3.0%, and 1.3%, respectively.
A 10% or greater reduction in 3D-LVEF was recorded in 19.0% of people who received placebo, 11.4% of those who received bisoprolol monotherapy, 11.5% of those who received ramipril monotherapy, and 6.8% of individuals who received both drugs.
Similarly, global longitudinal strain (GLS) worsened by 6.0%, on average, in the placebo arm and by 0.6% and 1.5% in the bisoprolol and ramipril monotherapy arms, respectively. In the bisoprolol plus ramipril arm, there was a 0.1% GLS improvement at 12 months, relative to baseline.
The proportions with a 10% or greater reduction in GLS were 35.7%, 13.6%, 15.9%, and 13.6% with placebo, bisoprolol, ramipril, and bisoprolol plus ramipril, respectively.
When Meattini et al combined the data, they found that bisoprolol treatment, either alone or in combination with ramipril, was associated with significantly better outcomes than no bisoprolol use, independent of patient- and treatment-related characteristics.
Conversely, the impact of ramipril monotherapy or combination therapy was not significantly greater than that observed in the groups that did not receive ramipril.
Furthermore, “[t]he benefit related to a cardioprotective strategy was most evident in physically healthy and younger patients and patients without comorbidities, thus confirming that a cardioprotective strategy should be highly considered for all patients and not only for those classically considered at high risk,” the authors write in JAMA Oncology.
Meattini and team conclude that although their findings reinforce “the importance of a cardioprotective strategy for early patients with [breast cancer] who received an anthracycline-based chemotherapy,” the data “will have to be confirmed at the final results analysis.”
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