Adjuvant breast cancer therapy, while beneficial in prolonging survival, has been shown to have harmful effects on the heart, prompting some providers to prescribe neurohormonal blocking agents to attenuate the myocardial damage. The original PRADA trial showed that candesartan and metoprolol helped prevent a decline in LVEF in patients on adjuvant therapy. To date, however, smaller studies have not shown a similar benefit to neurohormonal blockade. In a late breaking clinical trial session on May 16 at the 2021 American College of Cardiology Scientific Sessions meeting, Dr. Siri Lagethon Heck of Akershush University Hospital in Oslo, Norway, presented the long-term follow up results of the PRADA trial.
In this 2×2 factorial, randomized placebo-controlled trial, participants were randomized to receive either placebo or the combination of candesartan and metoprolol. 130 participants were enrolled and randomized to receive one of four treatments, as described in the following table:
Participants were well randomized with a median age of 51 years. At least 75% of participants received Taxanes, and 25% received trastuzumab as part of their adjuvant therapy. All participants received the study drug during adjuvant therapy only. Immediately after adjuvant therapy, there was a modest decline in left ventricular ejection fraction that was attenuated by candesartan, as previously published in the PRADA trial results. At two year follow up, however, LVEF declined by less than one percentage point in both groups, with no significant difference in either group.
Further analyses showed that while metoprolol attenuated troponin elevation during the study period, there was no difference in troponin between the two groups at 2 years. Cardiac MRI analysis did show more of a decrease in Left ventricular end diastolic volume and an attenuation in the decline of global longitudinal strain, suggesting a remodeling benefit for the drug.
“What is critical to our field is to understand that we need to target cardioprotective therapy based on risk, and work on phenotyping patients according to their risk profile before treatment,” said Dr. Bonnie Ky of the University of Pennsylvania in response to the results. The authors of the study agreed, concluding that widespread use of cardioprotective medications may not be necessary for all patients undergoing breast cancer therapy.
The authors acknowledge the limitations of their study, namely that 18% of their participants did not have a cardiac MRI at the two year follow up, and that the decline in LVEF was less than expected based on contemporary literature.
The study has been published in Circulation (https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.121.054698).
Additional background and information can be found here.