First author, country, year of publication (study name) |
Study design |
Study period |
Region |
Mean follow-up (months) |
Patients (n) |
Study (n) |
Control (n) |
All-cause mortality—unadjusted HR (95% CI) |
All-cause mortality—adjusted HR (95% CI) |
HFrEF |
Randomized controlled trials—beneficial treatment effect |
Packer, USA, 2001 (COPERNICUS)128 |
RCT |
1997–2000 |
Multiregional |
10 |
2289 |
1156 |
1133 |
RR: 0.65 (0.52–0.81; P < 0.00013) |
— |
MERIT-HF Study Group, Sweden, 1999 (MERIT-HF)129 |
RCT |
1997–1998 |
Europe, USA |
12 |
3991 |
1990 |
2001 |
RR: 0.66 (0.53–0.81; P < 0.0001) |
— |
CIBIS Investigators, UK, 1999 (CIBIS-II)130 |
RCT |
— |
Europe |
16 |
2647 |
1327 |
1320 |
0.66 (0.54–0.81; P < 0.0001) |
— |
Packer, USA, 1996 (US Carvedilol HF Study Group)131 |
RCT |
1993–1995 |
USA |
7 |
1094 |
696 |
398 |
RR: 0.35 (0.20–0.61; P < 0.001) |
— |
Randomized controlled trials—neutral treatment effect |
van Veldhuisen, Netherlands, 2009 (SENIORS)132 |
Pre-specified subgroup analysis of RCT (EF <35%) (≥70 years) |
2000–2002 |
Europe |
21 |
1359 |
678 |
681 |
0.84 (0.66–1.08) |
— |
BEST Investigators, USA, 2001 (BEST)133 |
RCT |
1995–1998 |
USA, Canada |
24 |
2708 |
1354 |
1354 |
0.90 (0.78–1.02; P > 0.10) |
— |
ANZ HF Research Collaborative Group, New Zealand, 1997 (ANZ)134 |
RCT (IHD) |
— |
Australia, New Zealand |
19 |
415 |
207 |
208 |
RR: 0.76 (0.42–1.36; P > 0.1) |
— |
CIBIS Investigators, France, 1994 (CIBIS-I)135 |
RCT |
1989–1992 |
Europe |
23 |
641 |
320 |
321 |
— |
RR: 0.80 (0.56–1.15) |
Observational studies—beneficial treatment effect |
Cadrin-Tourigny, Canada, 2017 (AF-CHF)47 |
Post hoc analysis of RCT (PSM) (AF) |
2001–2005 |
Multiregional |
37a |
655 |
426 |
229 |
— |
0.72 (0.55–0.95; P < 0.018) |
Bhatia, USA, 2015 (Alabama HF Project)48 |
Retrospective cohort study (PSM) (≥65 years) |
1998–2001 |
USA |
48 |
760 |
380 |
380 |
— |
0.81 (0.67–0.98) |
Ushigome, Japan, 2015 (2. CHART-2)30 |
Prospective cohort study |
2006–2010 |
Japan |
36 |
1360 |
870 |
490 |
— |
0.59 (0.44–0.81; P < 0.001) |
Del Carlo, Brazil, 201449 |
Retrospective cohort study |
1992, 1994, 1996, 1999, 2005–2006 |
Brazil |
12 |
333 |
199 |
134 |
0.3 (0.2–0.5; P < 0.001) |
0.3 (0.2–0.5; P < 0.001) |
Liu, China, 201428 |
Prospective cohort study |
2005–2010 |
China |
52a |
2154 |
1471 |
683 |
— |
0.75 (0.57–0.999; P < 0.049) |
Lund, Sweden, 2014 (Swedish HF Registry)50 |
Registry (PSM) |
2005–2012 |
Sweden |
23a |
6081 |
4054 |
2027 |
— |
0.89 (0.82–0.97; P < 0.005) |
El-Refai, USA, 201351 |
Retrospective cohort study |
2000–2008 |
USA |
25a |
1094 |
927 |
167 |
— |
0.26 (0.17–0.40; P < 0.001) |
Xu, China, 201352 |
Retrospective cohort study |
2007–2012 |
China |
31a |
685 |
555 |
130 |
— |
0.69 (0.50–0.95; P < 0.021) |
Teng, Australia, 2010 (WAHMD)46 |
Retrospective cohort study |
1996–2006 |
Australia |
12 |
225 |
100 |
125 |
— |
0.53 (0.32–0.87; P < 0.011) |
Hernandez, USA, 2009 (OPTIMIZE-HF)53 |
Registry (≥65 years) |
— |
USA |
12 |
3001 |
1800 |
1201 |
0.65 (0.57–0.73) |
0.77 (0.68–0.87) |
Miyagishima, Japan, 200954 |
Retrospective cohort study |
2000–2004 |
Japan |
36 |
431 |
297 |
134 |
— |
0.48 (0.32–0.73) |
Fauchier, France, 2009 (41% HFrEF)55 |
Retrospective cohort study (AF) |
2000–2004 |
France |
29 |
1269 |
449 |
820 |
— |
RR: 0.60 (0.40–0.89; P < 0.01) |
Pascual-Figal, Spain, 200856 |
Registry (>70 years) |
2002–2003 |
Spain |
31a |
272 |
139 |
133 |
0.45 (0.31–0.65; P < 0.001) |
0.53 (0.34–0.80; P < 0.003) |
Jost, Germany, 2005 (Ludwigshafen HF Registry) (1. 'Trial patients')57 |
Registry |
1995–2004 |
Germany |
31 |
278 |
166 |
112 |
— |
0.57 (0.38–0.86) |
Jost, Germany, 2005 (Ludwigshafen HF Registry) (2. 'Non-trial patients')57 |
Registry |
1995–2004 |
Germany |
31 |
397 |
204 |
193 |
— |
0.72 (0.53–0.97) |
Bobbio, Italy, 2003 (BRING-UP)58 |
Prospective cohort study |
1998 |
Italy |
12 |
2843 |
1582 |
1261 |
RR: 0.46 (0.38–0.57) |
0.64 (0.48–0.86) |
Observational studies—neutral treatment effect |
Ushigome, Japan, 2015 (1. CHART-1)30 |
Prospective cohort study |
2000–2005 |
Japan |
36 |
543 |
184 |
359 |
— |
0.87 (0.50–1.50; P < 0.610) |
Huan Loh, UK, 200759 |
Retrospective cohort study |
— |
UK |
36a |
900 |
738 |
162 |
0.54 (0.40–0.73; P < 0.001) |
0.73 (0.53–1.02; P < 0.067) |
HFpEF |
Randomized controlled trials—neutral treatment effect |
Yamamoto, Japan, 2013 (J-DHF)136 |
PROBE |
2004–2009 |
Japan |
38 |
245 |
120 |
125 |
0.99 (0.53–1.86; P < 0.975) |
— |
van Veldhuisen, Netherlands, 2009 (SENIORS)132 |
Pre-specified subgroup analysis of RCT (EF >35%) (≥70 years) |
2000–2002 |
Europe |
21 |
752 |
380 |
372 |
0.91 (0.62–1.33; P < 0.718) |
— |
Observational studies—beneficial treatment effect |
Ruiz, Spain, 201660 |
Prospective cohort study (PSM) |
2006–2015 |
Spain |
22a |
1970 |
985 |
985 |
RR: 0.76 (0.70–0.83; P < 0.001) |
0.78 (0.71–0.85; P < 0.001) |
Lund, Sweden, 2014 (Swedish HF Registry)50 |
Registry (PSM) |
2005–2012 |
Sweden |
23a |
8244 |
5496 |
2748 |
— |
0.93 (0.86–0.996; P < 0.04) |
El-Refai, USA, 201351 |
Retrospective cohort study |
2000–2008 |
USA |
25a |
741 |
570 |
171 |
— |
0.43 (0.27–0.68; P < 0.001) |
Nevzorov, Israel, 201261 |
Retrospective cohort study |
2001–2005 |
Israel |
24 |
345 |
154 |
191 |
— |
0.69 (0.47–0.99; P < 0.046) |
Gomez-Soto, Spain, 201162 |
Prospective cohort study (propensity score adjusted) |
2001–2005 |
Spain |
30a |
1085 |
378 |
707 |
RR: 0.37 (0.21–0.50; P < 0.001) |
0.72 (0.58–0.84) |
Teng, Australia, 2010 (WAHMD)46 |
Retrospective cohort study |
1996–2006 |
Australia |
12 |
284 |
101 |
183 |
— |
0.62 (0.39–0.99; P < 0.048) |
Fauchier, France, 2009 (35% HFpEF)55 |
Retrospective cohort study (AF) |
2000–2004 |
France |
29 |
1269 |
449 |
820 |
— |
RR: 0.45 (0.26–0.80; P < 0.006) |
Shah, USA, 2008 (NHC)32 |
Retrospective cohort study (≥65 years) |
1998–1999, 2000–2001 |
USA |
36 |
13 533 |
4562 |
8971 |
— |
RR: 0.92 (0.87–0.97) |
Dobre, Netherlands, 200763 |
Prospective cohort study (propensity score adjusted) |
2000–2005 |
Netherlands |
25 |
443 |
227 |
216 |
— |
0.57 (0.37–0.88; P < 0.01) |
Observational studies—neutral treatment effect |
Ushigome, Japan, 2015 (1. CHART-1)30 |
Prospective cohort study |
2000–2005 |
Japan |
36 |
463 |
104 |
359 |
— |
0.89 (0.45–1.75; P < 0.734) |
Ushigome, Japan, 2015 (2. CHART-2)30 |
Prospective cohort study |
2006–2010 |
Japan |
36 |
2316 |
1018 |
1298 |
— |
0.94 (0.73–1.22; P < 0.654) |
Patel, USA, 2014 (OPTIMIZE-HF)64 |
Registry (PSM) (≥65 years) |
2003–2004 |
USA |
72 |
2198 |
1099 |
1099 |
— |
0.99 (0.90–1.10; P < 0.897) |
Hernandez, USA, 2009 (OPTIMIZE-HF)53 |
Registry (≥65 years) |
— |
USA |
12 |
4153 |
1621 |
2532 |
0.87 (0.77–0.97) |
0.94 (0.84–1.07) |
Mixed/unspecified HF phenotype |
Randomized controlled trials—neutral effect |
Flather, UK, 2005 (SENIORS) (65% HFrEF, 35% HFpEF)137 |
RCT (≥70 years) |
2000–2002 |
Multiregional |
21 |
2128 |
1067 |
1061 |
0.88 (0.71–1.08; P < 0.21) |
— |
Observational studies—beneficial treatment effect |
Katz, Israel, 2016 (HFSIS) (38% HFrEF, 15% HFmrEF, 22% HFpEF, 26% unknown)65 |
Prospective cohort study |
2003 |
Israel |
120 |
2402 |
1481 |
921 |
— |
0.83 (0.77–0.89; P < 0.001) |
Maison, France, 201366 |
Registry (propensity score adjusted) |
2000 |
France |
96 |
281 |
101 |
180 |
— |
0.54 (0.34–0.84) |
Gastelurrutia, Spain, 2012 (75% HFrEF, 25% HFrEF)45 |
Prospective cohort study |
2001–2008 |
Spain |
44a |
960 |
776 |
184 |
— |
0.51 (0.39–0.66; P < 0.001) |
Marijon, France, 2010 (EVADEF)67 |
Prospective cohort study (ICD) |
2001–2003 |
France |
22 |
1030 |
721 |
309 |
0.53 (0.30–0.91; P < 0.02) |
0.56 (0.32–0.98; P < 0.04) |
Teng, Australia, 2010 (WAHMD) (24% HFrEF, 30% HFpEF, 46% unknown)46 |
Retrospective cohort study |
1996–2006 |
Australia |
12 |
944 |
318 |
626 |
— |
0.68 (0.53–0.86; P < 0.002) |
Fauchier, France, 2009 (41% HFrEF, 35% HFpEF, 24% unknown)55 |
Retrospective cohort study (AF) |
2000–2004 |
France |
29 |
1269 |
449 |
820 |
0.59 (0.45–0.78; P < 0.0002) |
0.60 (0.43–0.84; P < 0.003) |
Jordán, Spain, 2009 (BADAPIC) (77% HFrEF, 23% HFpEF)68 |
Registry |
2000–2002 |
Spain |
35 |
3162 |
2242 |
920 |
— |
RR: 0.82 (0.47–0.95) |
Dobre, Netherlands, 2007 (55% HFrEF, 45% HFpEF)69 |
Prospective cohort study (propensity score adjusted) |
2000–2004 |
Netherlands |
22 |
625 |
308 |
317 |
|
0.55 (0.39–0.78; P < 0.001) |
Keyhan, Canada, 2007 (1. female cohort)70 |
Retrospective cohort study (≥65 years) |
1998–2003 |
Canada |
30 |
14 693 |
7584 |
7109 |
0.67 (0.64–0.70) |
0.79 (0.75–0.83) |
Keyhan, Canada, 2007 (2. male cohort)70 |
Retrospective cohort study (≥65 years) |
1998–2003 |
Canada |
30 |
13 144 |
6499 |
6645 |
0.64 (0.61–0.67) |
0.76 (0.72–0.80) |
Chan, USA, 2005 (CHS) (19% HFrEF, 36% HFpEF, 45% unknown)71 |
Prospective cohort study (≥65 years) |
1989–2000 |
USA |
120 |
950 |
157 |
793 |
0.74 (0.56–0.98) |
0.74 (0.56–0.98) |
Tandon, Canada, 2004 (75% HFrEF, 25% HFpEF)41 |
Prospective cohort study |
1989–2001 |
Canada |
32a |
1041 |
475 |
566 |
— |
OR: 0.52 (0.39–0.70) |
Maggioni, Italy, 2003 (BRING-UP) (1. no BB vs. continued BB)72 |
Registry |
1998 |
Italy |
12 |
2226 |
771 |
1455 |
— |
0.74 (0.55–0.99; P < 0.045) |
Maggioni, Italy, 2003 (BRING-UP) (2. no BB vs. initiated BB)72 |
Registry |
1998 |
Italy |
12 |
2320 |
865 |
1455 |
— |
0.60 (0.45–0.80; P < 0.0003) |
McCullough, USA, 2003 (REACH)73 |
Retrospective cohort study |
1995–1998 |
USA |
12 |
1317 |
647 |
670 |
— |
OR: 0.75 (0.57–0.98; P < 0.04) |
Sin, Canada, 2002 (19% HFrEF, 36% HFpEF, 45% unknown)44 |
Retrospective cohort study (≥65 years) (propensity score adjusted) |
1994–1998 |
Canada |
21a |
11 942 |
1162 |
10 780 |
— |
0.72 (0.65–0.80) |
McAlister, Canada, 1999 (78% HFrEF, 22% HFpEF)74 |
Prospective cohort study |
1989–1995 |
Canada |
17 |
566 |
147 |
419 |
— |
OR: 0.5 (P < 0.006–95% CI not reported) |
Observational studies—neutral treatment effect |
Ushigome, Japan, 2015 (1. CHART-1) (54% HFrEF, 46% HFpEF)30 |
Prospective cohort study |
2000–2005 |
Japan |
36 |
1006 |
288 |
718 |
— |
0.96 (0.63–1.44; P < 0.829) |
Ushigome, Japan, 2015 (1. CHART-2) (37% HFrEF, 63% HFpEF)30 |
Prospective cohort study |
2006–2010 |
Japan |
36 |
3676 |
1886 |
1790 |
— |
0.82 (0.68–1.00; P < 0.055) |
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