Beta-Blockers for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: An Updated Meta-Analysis of Randomized Clinical Trials

Table 1

Characteristics of the included studies.

Study

Number

Age() or (range)

Gender (female %)

Malignancy (%)

Beta-blocker regimen

ANT dosage(SD)

Radiation (%)

Primary end point

EF cut off

IA

CA

IA

CA

IA

CA

IA

CA

IA

CA

Kalay et al. [5]

25

25

.8

22(88%)

21(84%)

Breast cancer 34 (68%); Lymphoma 9 (18%); Others 7 (14%)

Carvedilol

DOX 525.3 mg/m^2; EPI 787.9 mg/m^2

DOX 513.6 mg/m^2; EPI 770.4 mg/m^2

0

0

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters; (4) Troponin

LVEF <50%

Georgakopoulos et al. [17]

85

40

20 (48%)

19(47%)

Lymphoma 125 (100%)

Metoprolol

DOX 387.5 mg/m^2

DOX 386.4 (5.7) mg/m^2

8 (19)

9 (23)

(1) Echocardiographic parameters; (2) Pulsed tissue Doppler imaging parameters

LVEF <50%; LVEF drop >10%

Salehi et al. [12]

44

22

32(72.2%)

14(63.6%)

Lymphoma 19 (28.8%); Breast 47 (71.2%)

Carvedilol

DOX 525.32 mg/m^2; EPI 767.57 mg/m^2

DOX 540.3 mg/m^2; EPI 768.44 mg/m^2

0

0

(1) Echocardiographic parameters; (2) Pulsed tissue Doppler imaging parameters

NA

Liu et al. [16]

20

20

53 (39–68)

53 (37–65)

NA

NA

Breast cancer 40 (100%)

Carvedilol

NA

NA

NA

NA

(1) Electrocardiogram; (2)Echocardiographic parameters; (3)Troponin I

LVEF<45%

Kaya et al. [19]

27

18

100%

100%

Breast cancer 45(100%)

Nebivolol

DOX 257 (29) mg/m^2; EPI 361(88) mg/m^2

DOX 235(48) mg/m^2; EPI 348(84) mg/m^2

7 (26%)

5 (28%)

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters; (4) Troponin I; (5) Plasma BNP

LVEF <45%; LVEF drop >10%

Bosch et al. [15]

45

45

18 (40%)

21 (47%)

Acute leukemia 36 (40); Hodgkin lymphoma 9 (10); Non-Hodgkin lymphoma 23 (26); Multiple myeloma 22 (24)

Carvedilol

290(189) mg/m^2

241(162) mg/m^2

12 (27)

4 (9)

(1) Mortality; (2) Echocardiographic parameters; (3) CMRI; (4) Pulsed tissue Doppler imaging parameters; (5) Troponin I; (6) Plasma BNP

LVEF <45%; LVEF drop >10%

Elitok et al. [9]

40

40

40(100%)

40(100%)

Breast cancer 80 (100%)

Carvedilol

DOX 535.6 mg/m^2

DOX 523.3 mg/m^2

0

0

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters

(1) LVEF drop >10%; (2) LVEF drop>5% accompanying signs or symptoms of HF

Heck et al. [18]

62

58

62(100%)

58(100%)

Breast cancer 120(100%)

Metoprolol

NA

NA

45(72.5%)

40(66.7%)

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters

(1) LVEF drop >10%; (2) LVEF drop>5% accompanying signs or symptoms of HF; (3) Death

Jhorawat et al. [10]

27

27

4(14.8%)

9(33.3%)

Lymphoma 53 (98); Acute leukemia 1 (2)

Carvedilol

DOX 267.36(76.126) mg/m^2

DOX 252.65(77.82) mg/m^2

0

0

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters; (4) Troponin I; (5) Plasma BNP

LVEF <50%; Drop >10%-30%

Tashakori et al. [13]

30

40

30(100%)

40(100%)

Breast cancer70(100%)

Carvedilol

DOX 240 mg/m^2

DOX 240 mg/m^2

0

0

(1) Echocardiographic parameters; (2) Pulsed tissue Doppler imaging parameters

LVEF <50%; Drop >10%-30%

Nabati et al. [11]

46

45

100%

100%

Breast cancer 91 (100)

Carvedilol

DOX 348.56 (40.34) mg/m^2

DOX 359.91 (27.13) mg/m^2

0

0

(1) Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters; (4) Troponin I

LVEF drop of >5% to <55% with HF; LVEF drop of >10% to <55% without HF

Avila et al. [6]

96

96

96(100%)

96(100%)

Breast cancer 192 (100)

Carvedilol

DOX 240 mg/m^2

DOX 240 mg/m^2

0

0

(1)Mortality; (2) Echocardiographic parameters; (3) Pulsed tissue Doppler imaging parameters; (4)Troponin I; (5) Plasma BNP

LVEF <50%; LVEF drop >10%

Lee et al. [14]

70

43

70(100%)

43(100%)

Breast cancer 113 (100)

Carvedilol

DOX 240 mg/m^2

DOX 240 mg/m^2

50(71.4%)

35(81.4%)

(1) Presence of DISC; (2) Echocardiographic parameters

NA

Wihandono et al. [22]

26

25

26(100%)

25(100%)

Breast cancer 51 (100)

Lisinopril and Bisoprolol

DOX 579.48(65.10) mg

DOX 579.48 (65.10)mg

NA

NA

(1) Echocardiography paramenters

NA

Cochera et al. [20]

30

30

30(100%)

30(100%)

Breast cancer 60 (100)

Nebivolol

DOX 521(6) mg/m^2

DOX 519(9) mg/m^2

0

0

(1) Echocardiographic parameters

LVEF <50%; LVEF drop >10%

Livi et al. [21]

45

42

42(100%)

45(100%)

Breast cancer 174(100%)

Bisoprolol

NA

NA

26(62%)

27(60%)

(1) Echocardiographic parameters

1.LVEF drop >10%

IA: interverion arm; CA: control arm; ANT: anthracyclines; DOX: doxorubicin; EPI: epirubicin: LVEF: left ventricular ejection fraction; HF: heart failure; NA: not available, DISC: doxorubicin-induced subclinical cardiotoxicity; BNP: brain natriuretic peptide. The cumulative dose belongs to different anthracyclines.