Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients Receiving Combination Therapy of Candesartan and Carvedilol for Primary Prevention: A Prospective Longitudinal Study.

BACKGROUND: The use of renin-angiotensin system inhibitors and beta-blockers for primary prevention of cancer therapy-related cardiac dysfunction (CTRCD) remains controversial. This study investigated the incidence, severity and predictors of CTRCD under cardioprotective therapy with a combination of candesartan and carvedilol.

METHODS: We included 851 subjects with a normal left ventricular ejection fraction (LVEF) (> 55%) who were scheduled to receive chemotherapy and/or trastuzumab (TZ) for breast cancer. Candesartan plus carvedilol were administered on the first day of chemotherapy or TZ and continued during and after cancer therapy. Patients underwent serial real-time three-dimensional (3D) echocardiograms before initiation of chemotherapy or TZ, every 3 months during cancer therapy, 6 months after completion of cancer therapy, and annually thereafter. CTRCD was defined by the European Society of Cardiology definitions using LVEF and global longitudinal strain (GLS) derived from 3D-echocardiographic images.

RESULTS: A total of 577 patients (257 anthracycline [AC]/non-TZ, 111 AC/TZ, 47 non-AC/TZ, and 162 non-AC/non-TZ) were analyzed. During a median follow-up of 17.9 months, 24.6% of patients (28.8% AC/non-TZ vs. 43.2% AC/TZ vs. 21.3% non-AC/TZ vs. 6.2% non-AC/non-TZ; P < 0.001) developed CTRCD. No symptomatic CTRCD was observed throughout the study period and most CTRCD cases had mild severity (96.5%). Older age, hypertension, and lower LVEF and better GLS value at baseline, and stage II disease or higher, but not the use of AC and/or TZ, were associated with the risk of developing CTRCD. For patients receiving AC and/or TZ, hypertension was a predictor of CTRCD in both the low (adjusted hazard ratio [HR], 5.471; 95% confidence interval [CI], 2.440-12.269; P < 0.001) and intermediate-to-high (adjusted HR, 2.147; 95% CI, 1.329-3.469; P = 0.002) baseline cardiovascular toxicity risk groups.

CONCLUSION: In a primary prevention strategy with combined therapy of candesartan and carvedilol, asymptomatic CTRCD was still not uncommon and hypertension was a strong risk factor of CTRCD in breast cancer patients treated with cardiotoxic cancer therapy.