American College of Cardiology

American College of Cardiology

Source:

Heck SL, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).

Disclosures: Heck and Ky report no relevant financial disclosures. Please see the study for the other authors’ relevant financial disclosures.
May 16, 2021
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Cardioprotective therapies fail to prevent LVEF decline in early breast cancer treatment

Source:

Heck SL, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).

Disclosures: Heck and Ky report no relevant financial disclosures. Please see the study for the other authors’ relevant financial disclosures.
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Neurohormonal blockade using candesartan and/or metoprolol for women undergoing treatment for early breast cancer was not significantly protective against minor long-term decline in left ventricular ejection fraction, a speaker reported.

According to data presented at the virtual American College of Cardiology Scientific Session, concomitant cardioprotective therapies during early breast cancer treatment may not be necessary without the presence of preexisting CVD.

doctor showing patient mammogram
Source: Adobe Stock

The study was simultaneously published in Circulation.

Siri Lagethon Heck

“If patients don’t have preexisting heart conditions or high cardiovascular risks from the start — for example, hypertension or diabetes — it seems to be relatively safe to administer adjuvant therapy,” Siri Lagethon Heck, MD, PhD, cardiovascular radiologist at Akershus University Hospital in Lørenskog, Norway, said in a press release. “In this patient group, the therapy isn’t as dangerous as previously thought, and in general, patients should not be afraid that their cancer therapy will harm their heart.”

In the long-term follow-up results of PRADA, a 2x2 factorial, randomized, placebo-controlled, double-blind trial, researchers enrolled 120 women receiving treatment for early breast cancer with anthracyclines, with or without anti-human epidermal growth factor receptor 2 (HER2) antibodies, and radiotherapy. Researchers hypothesized that long-term decline in cardiac function may be prevented by using concomitant metoprolol, a beta-blocker, and/or candesartan, an angiotensin receptor blocker, during treatment for early breast cancer.

Participants were randomly assigned to a combination of metoprolol and candesartan; metoprolol and placebo; candesartan and placebo; or double placebo in addition to adjuvant breast cancer therapy.

Baseline characteristics such as age (median age, 51 years), BMI, smoking status and presence of hypertension and diabetes were similar in all four groups.

The primary outcome was change in LVEF assessed by cardiac MRI from baseline to a median of 23 months follow-up, and secondary outcomes included changes in LV volumes and cardiac troponin I and T concentrations.

Researchers reported that, from baseline to follow-up, decline in LVEF in patients receiving candesartan was 1.7 percentage points (95% CI, 0.5-2.8), compared with 1.8 percentage points (95% CI, 0.6-3) among patients not receiving candesartan in the intention-to-treat analysis (P for between-group difference = .91).

Among patients receiving metoprolol, decline in LVEF was 1.6 percentage points (95% CI, 0.4-2.7) compared with 1.9 percentage points (95% CI, 0.7-3) in patients not receiving metoprolol (P for between-group difference = .73).

Candesartan treatment was associated with an average reduction in the secondary outcome measure of LV end-diastolic volume of 5 mL compared with an increase of 2 mL among patients not receiving candesartan (P = .021).

Researchers also observed that patients not receiving candesartan experienced increased LV end-systolic volumes of about 3 mL compared with patients receiving candesartan, who experienced no change (P = .086).

Researchers reported no effect of concomitant metoprolol and/or candesartan during treatment for early breast cancer on change in cardiac troponins.

Moreover, there was a slight decline in global longitudinal strain that was attenuated by candesartan (0.2 percentage points; 95% CI, –0.3 to 0.8; vs. 1 percentage point in patients not receiving candesartan; 95% CI, 0.5-1.5; P for between-group difference = .046).

Additionally, there were no between-group differences in incidence of HF or decline in LVEF.

“Therapy with candesartan and metoprolol during adjuvant therapy for early breast cancer did not protect against the decline in systolic function at follow-up 2 years after randomization,” Heck said during the presentation. “As decline in systolic function was small and not prevented by the intervention, routine cardioprotective therapy with angiotensin receptor blockers and beta-blockers seems not to be required for most patients.”

Bonnie Ky

Discussant Bonnie Ky, MD, MSCE, director of the Penn Cardio-Oncology Translational Center of Excellence at Penn Medicine, framed these results in the context of the short-term data from the PRADA study presented in 2015.

“In candesartan, metoprolol or placebo, there is no effect at 2 years as measured by cardiac MRI and cardiac injury measures such as troponin; but a very modest protective effect on end-diastolic volume and global longitudinal strain with candesartan,” Ky said. “In contrast, the short-term PRADA results in 2015 suggested there was a 2.6% decline in EF in the no candesartan group, which was attenuated in those patients treated with candesartan, potentially suggesting that candesartan may have a protective effect. There are many important strengths of this study related to the design and execution and the careful phenotyping using cardiac MRI, echo and biomarkers in the long-term follow-up. A critical take-home message for our field is that we need to target cardioprotective therapy according to risk and personalize cardioprotective therapy according to who’s at increased risk, be it by treatment factors or host factors.”

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