After a modest initial sign of profit, candesartan cilexetil (Attacking, Cheplapharm) showed no effect on key markers of cardiac health 2 years after treatment in early-stage patients Lung cancer at random PRADA test.
The 2015 study was held at the time as the largest randomized trial in breast cancer to analyze the effects of angiotensin receptor blockade with candesartan and the β-blocker. metoprolol, both against placebo, in cardiac dysfunction. All 120 patients received adjuvant anthracycline cancer therapy with or without trastuzumab and radiation therapy, all known to have cardiotoxic adverse effects.
As before reported, the main outcome of the change in left ventricular ejection fraction (LVEF) from baseline was attenuated by approximately 3% after cancer treatment in women who took a daily dose of 32 mg candesartan in compared to those receiving placebo (Pg = 0.026).
However, at 2 years, serial MRI monitoring showed that the benefit of LVEF over placebo had disappeared (mean Δ, –1.7% vs. –1.8%; Pg =, 91). Candesartan also had no significant effect on troponin I levels (Pg = .56).
Left ventricular end diastolic volume was significantly reduced with candesartan compared with placebo (mean mean, –5 ml vs 2 ml; Pg = 0.021), and the decrease in overall longitudinal deformation was smaller (mean Δ, –0.2% vs 1.0%; Pg = .046).
“This suggests that candesartan has favorable remodeling effects, but the effect sizes were quite small and the clinical relevance of these changes more than a year after endotherapy is unclear,” the author said. of the study, Siri Lagethon Heck, MD, PhD, Akershus University Hospital, Lørenskog, Norway. , dit.
Metoprolol could not reverse its first and poor performance, without exerting any effect at 2 years on LVEF (Pg = 0.73), final diastolic volume RV (Pg = 0.78), or global longitudinal deformation (Pg = .34) vs placebo.
The β-blocker had reduced the increase in troponin I levels from baseline, but the difference was no longer significant after 2 years (Pg = .76), according to the results published inside Circulation and presented simultaneously at the 2021 American College of Cardiology (ACC) scientific session.
During a discussion of the last trial, Heck noted that the decrease in LVEF was lower than expected and that patients had a low risk, with few comorbidities, a baseline LVEF of at least 50%, and relatively high dose reception. anthracycline casualties.
“Cardioprotective therapy administered during adjuvant breast cancer therapy may not be necessary, as decreased systolic function was less and was not prevented with neurohormonal blockade,” he said.
Speaker Bonnie Ky, MD, MSCE, director of the Center for Translational Cardio-Oncological Excellence, University of Pennsylvania, Philadelphia, said the study has many important strengths, including careful phenotyping and serial follow-up with cardiac MRI.
“What I think is a critical message to take away for our field is that we need to target cardioprotective therapy according to risk and customize therapy according to who has a higher risk, either by treatment factors or by factors host, ”he said.
In a press conference that highlighted the study, Ana Barac, MD, PhD, director of the cardio-oncology program at the MedStar Heart and Vascular Institute, Washington, DC, said the results were reassuring in the fact that no one developed heart attack but also point to the need to design cardiovascular prevention trials in cancer patients based on their cardiovascular risk.
“The elephant in the room is that cancer practice sometimes demands what the inclusion criteria are for anthracyclines and trastuzumab, which have been given in some of your patients, but they are only approved for its normal functioning and we all know that you see patients who do not have a normal function and who are the most at risk patients, ”he said. “I think the next studies, which I hope your group will take on as well, will include this group of high-risk patients and show how we can improve their outcomes.”
Heck did not report any relevant financial relationships. Ky reported consultant fees / Cytokinetics fees; other relationships with Corvia, Impulse Dynamics, Mardil Medical and UpToDate; and acting as a speaker for Roche. Barac reported on his participation in an ACI Clinical data security monitoring board.
Circulation. Published online May 16, 2021. Summary
Scientific Session of the American College of Cardiology (ACC) 2021. Abstract 406-17. Filed May 16, 2021.