PRADA: Do Cardioprotective Drugs During Adjuvant Therapy For Breast Cancer Improve CV Outcomes?

Cardioprotective drugs during adjuvant therapy for early-stage breast cancer do not protect against long-term decline in cardiac function, according to new data from the PRADA trial presented May 16 during ACC.21 and simultaneously published in Circulation.

In the single center, double-blind trial, Siri Lagethon Heck, MD, PhD, et al., assessed the long-term impact of candesartan cilexetil (32 mg), metoprolol succinate (100 mg), a combination, or a placebo on preventing a decrease in cardiac function and myocardial injury. Using a 2x2 factorial design, 120 patients with early-stage breast cancer receiving anthracycline-containing chemotherapy after surgery were randomized 1:1:1:1 to the four treatment arms. Cardiac MRI was performed at the start of the study and after a median of 23 months.

In the intention-to-treat analysis, no between-group differences were seen for the primary outcome of change in left ventricular ejection fraction (LVEF) assessed by cardiac MRI. The overall decline in LVEF was 1.7% and 1.8% in patients who did and did not take candesartan, and it was 1.6% and 1.9% in patients who did and did not take metoprolol. Results were similar for the per-protocol analysis and for low vs. high anthracycline doses.

Regarding secondary endpoints, end-diastolic volume was reduced with candesartan (by 5 ml) vs. an increase of 2 ml without candesartan, and end-systolic volume increased in patients not taking candesartan but not in those taking candesartan (3 ml vs. 0 ml). No effect was seen in cardiac troponins. The decline in global longitudinal strain was attenuated with candesartan but not metoprolol.

These findings suggest that cardioprotective medications aren't necessary during adjuvant therapy for patients without preexisting cardiovascular risk factors or at high cardiovascular risk, says Heck, the study's lead author. "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."

To advance efforts to prevent heart failure in these patients, the researchers are now conducting a separate, multicenter trial to test sacubitril/valsartan in more high-risk patients. They are also further analyzing data from PRADA to determine factors that may increase a person's risk for heart damage.

"We want to try to identify the patients who are at higher risk for heart problems and who might benefit more from cardioprotective drugs," the authors conclude. "With this information, we can really put the effort where the help is needed."

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia

Keywords: ACC Annual Scientific Session, ACC21, Dyslipidemias, Neoplasms

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