Does cardioprotective therapy with perindopril, bisoprolol, and trimetazidine prevent cardiotoxicity and reduce mortality in high-risk cancer patients undergoing antitumor treatment?
Primary pharmacological prevention with perindopril, bisoprolol, and trimetazidine preserves left ventricular systolic function and may reduce mortality in high-risk cancer patients undergoing cardiotoxic chemotherapy.
Aim Search for subclinical manifestations of cardiotoxicity in cancer patients at high and very high risk of cardiotoxicity and evaluation of the effectiveness of drug primary prevention during the antitumor treatment. Material and methods The study included 150 cancer patients with a high and very high Mayo Clinic (USA) Cardiotoxicity Risk Score. The main group consisted of 84 patients at high and very high risk of cardiotoxicity who were prescribed cardioprotective therapy, including a fixed combination of the angiotensin-converting enzyme inhibitor (ACEI) perindopril and the beta-blocker bisoprolol with trimetazidine. The comparison group consisted of 66 patients who refused cardioprotective drugs or had intolerance to them. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) and multibiomarker analysis, including measurements of troponin I (TnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), myeloperoxidase (MPO), soluble tumor suppressor type 2 (sST2), and two-dimensional echocardiography (EchoCG) with assessment of left ventricular global longitudinal systolic strain (LV GLS) before chemotherapy and 1, 3, 6, 9, and 12 months after the start of cardiotoxic antitumor therapy. Results In patients of the comparison group already at 6 months, the left atrial volume index (LAVI) was significantly increased, and the left ventricular end-diastolic volume index (LVEDVi) showed a tendency towards an increase reaching a significant difference by 9 months of observation. In the main group, these parameters did not significantly change during the study. At the last stage of observation, there were statistically significant differences in LAVI and LVEDVi between the compared groups. The dynamics of LV GLS in the compared groups showed multidirectional changes. In the main group, this parameter remained virtually unchanged while in the comparison group, it decreased by ≥15% in 13 patients and reached a statistically significant difference. Clinically pronounced cardiotoxicity and a decrease in the left ventricular ejection fraction (LVEF) developed in 7 of these patients. During the antitumor treatment, the concentrations of the biomarkers remained within the reference values, with the exception of TnI. The greatest differences between the groups were noted in the analysis of mortality. Thus, by the final visit, 13.1% of patients had died in the main group while in the comparison group, mortality was almost two times higher and reached 22.7%. Conclusion The study demonstrated clinical effectiveness of the cardioprotective therapy in cancer patients at high and very high risk of cardiotoxicity. The patients who did not receive the primary drug prevention of cardiovascular toxicity had a statistically significant impairment of the LV systolic function, an increased number of developed complications, and a higher mortality.
Vasyuk et al. (Wed,) studied this question.