***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Anthracycline ( ANT ) chemotherapy is associated with cardiotoxicity . Prevention with β-blockers remains controversial . OBJECTIVES This prospect i ve , r and omized , double-blind , placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity . METHODS The authors r and omized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction ( LVEF ) referred for ANT ( 240 mg/m2 ) to receive carvedilol or placebo until chemotherapy completion . The primary endpoint was prevention of a ≥10 % reduction in LVEF at 6 months . Secondary outcomes were effects of carvedilol on troponin I , B-type natriuretic peptide , and diastolic dysfunction . RESULTS Primary endpoint occurred in 14 patients ( 14.5 % ) in the carvedilol group and 13 patients ( 13.5 % ) in the placebo group ( p = 1.0 ) . No differences in changes of LVEF or B-type natriuretic peptide were noted between groups . A significant difference existed between groups in troponin I levels over time , with lower levels in the carvedilol group ( p = 0.003 ) . Additionally , a lower incidence of diastolic dysfunction was noted in the carvedilol group ( p = 0.039 ) . A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group ( 44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm ; p = 0.057 ) . CONCLUSIONS In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage , the authors noted a 13.5 % to 14.5 % incidence of cardiotoxicity . In this scenario , carvedilol had no impact on the incidence of early onset of LVEF reduction . However , the use of carvedilol result ed in a significant reduction in troponin levels and diastolic dysfunction . ( Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [ CECCY ] ; NCT01724450 ) Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2-overexpressing ( HER2-positive ) breast cancer is dose-independent cardiac dysfunction . Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure . We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity . Patients and Methods In this double-blinded , placebo-controlled trial , patients with HER2-positive early breast cancer were r and omly assigned to receive treatment with perindopril , bisoprolol , or placebo ( 1:1:1 ) for the duration of trastuzumab adjuvant therapy . Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle 17 for the determination of  left ventricular volumes and left ventricular ejection fraction ( LVEF ) . Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF . Results Thirty-three patients received perindopril , 31 received bisoprolol , and 30 received placebo .  Baseline demographic , cancer , and cardiovascular profiles were similar between groups . Study drugs were well tolerated with no serious adverse events . After 17 cycles of trastuzumab , indexed left ventricular end diastolic volume increased in patients treated with perindopril ( + 7 ± 14 mL/m2 ) , bisoprolol ( + 8 mL ± 9 mL/m2 ) , and placebo ( + 4 ± 11 mL/m2 ; P = .36 ) . In secondary analyses , trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients ( -1 ± 5 % ) relative to the perindopril ( -3 ± 4 % ) and placebo ( -5 ± 5 % ) groups ( P = .001 ) . Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis . Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy-related declines in LVEF ; however , trastuzumab-mediated left ventricular remodeling-the primary outcome -was not prevented by these pharmacotherapies BACKGROUND The use of antracycline ( ANT ) in breast cancer has been associated with adverse cardiac events . Two-dimensional ( 2D ) strain imaging ( SI ) can provide a more sensitive measure of altered left ventricular ( LV ) systolic function . We aim ed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT .  METHODS Patients receiving ANT  were r and omly assigned to the carvedilol- or placebo-receiving group . Each received an echocardiographic examination with conventional 2D echocardiography , pulsed tissue Doppler , and 2D SI prior to and 6 months post ANT treatment . RESULTS During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity . Both left ventricular ejection fraction ( LVEF ) and fractional shortening ( FS ) were within normal limits for all patients before and after ANT therapy . EF , FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy . The mean EF , FS , and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months . Though baseline SI parameters were similar between the groups , there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group . CONCLUSIONS These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose : Anthracyclines ( ANTs ) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer . We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity . Methods : In this r and omized , single-blind , placebo-controlled study , 91 women with recently diagnosed breast cancer undergoing ANT therapy  were r and omly assigned to groups treated with either carvedilol ( n = 46 ) or placebo ( n = 45 ) . Echocardiography was performed before and at 6 months after r and omization , and absolute changes in the mean left ventricular ejection fraction , left ventricular end diastolic volume , and left ventricular end systolic volume were determined . Furthermore , the percentage change in the left atrial ( LA ) diameter and other variables of left ventricular ( LV ) diastolic function , such as transmitral Doppler parameters , including early ( E wave ) and late ( A wave ) diastolic velocities , E/A ratio and E wave deceleration time , pulmonary venous Doppler signals , including forward systolic ( S wave ) and diastolic ( D wave ) velocities into LA , late diastolic atrial reversal velocity , and early diastolic tissue Doppler mitral annular velocity ( e ' ) were measured . In addition , tissue Doppler mitral annular systolic ( s ' ) velocity , as a marker of early stage of LV systolic dysfunction , E/e ' ratio , as a determinant of LV filling pressure , and troponin I level , as a marker of myocardial necrosis were measured . Results : At the end of follow-up period , left ventricular ejection fraction did not change in the carvedilol group . However , this parameter was significantly reduced in the control group ( P < 0.001 ) . Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group . In pulse Doppler studies , pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group . Moreover , a significant decrease in the mitral annuli early diastolic ( e ' ) and peak systolic ( s ' ) velocities and a significant increase in the E ( the peak early diastolic velocity)/e ' ratio in the control group were also observed . However , none of these variables were adversely changed at the end of follow-up in the carvedilol group . Furthermore , the TnI level was significantly higher in the control group than in the carvedilol group ( P = 0.036 ) at 30 days after the initiation of chemotherapy . Conclusions : Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity , even at low doses Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction . We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker c and esartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction ( LVEF ) associated with adjuvant , anthracycline-containing regimens with or without trastuzumab and radiation . Methods and results In a 2 × 2 factorial , r and omized , placebo-controlled , double-blind trial , we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker c and esartan cilexetil , the β-blocker metoprolol succinate , or matching placebos in parallel with adjuvant anticancer therapy . The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging . A priori , a change of 5 percentage points was considered clinical ly important . There was no interaction between c and esartan and metoprolol treatments ( P = 0.530 ) . The overall decline in LVEF was 2.6 ( 95 % CI 1.5 , 3.8 ) percentage points in the placebo group and 0.8 ( 95 % CI −0.4 , 1.9 ) in the c and esartan group in the intention-to-treat analysis ( P-value for between-group difference : 0.026 ) . No effect of metoprolol on the overall decline in LVEF was observed . Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation , concomitant treatment with c and esartan provides protection against early decline in global left ventricular function BACKGROUND We aim ed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients . METHODS In this small , prospect i ve , double-blind study , we r and omly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive  nebivolol 5 mg daily ( n=27 ) or placebo ( n=18 ) . Echocardiographic measurements and N-terminal pro-brain natriuretic peptide ( NT-pro-BNP ) levels were obtained at baseline and at 6-month of chemotherapy . RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline . At 6-month , the left ventricular ( LV ) end-systolic and end-diastolic diameters increased in the placebo group ( LVESD : 29.7 ± 3.4 to 33.4 ± 4.5 mm ; LVEDD : 47.2 ± 3.8 to 52.0 ± 4.6 mm , p=0.01 for both ) but remained unchanged in the nebivolol group ( LVESD : 30.4 ± 3.5 to 31.0 ± 3.6 mm , p=0.20 ; LVEDD : 47.0 ± 4.4 to 47.1 ± 4.0 mm , p=0.93 ) . The placebo group also had lower LVEF than the nebivolol group ( 57.5 ± 5.6 % vs. 63.8 ± 3.9 % , p=0.01 ) at 6-month . NT-pro-BNP level remained static in the nebivolol group ( 147 ± 57 to 152 ± 69 pmol/l , p=0.77 ) while it increased in the placebo group ( 144 ± 66 to 204 ± 73 pmol/l , p=0.01 ) . CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients Background & objectives : Adriamycin though considered as an effective anticancer drug , leads to irreversible cardiomyopathy ( CMP ) and congestive heart failure ( CHF ) . The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy 
    Output:
    
The prophylactic use of carvedilol exerted no impact on the early asymptomatic LVEF decrease but seemed to attenuate the frequency of clinical ly overt cardiotoxicity and prevent ventricular remodeling