Impact of β-blocker selectivity on long-term outcomes in congestive heart failure patients with chronic obstructive pulmonary disease

Figures & data

Table 1 Clinical characteristics of the study population

Variables	β-blocker use (n=86)	No β-blocker (n=46)	P-value	Carvedilol (n=52)	Bisoprolol (n=34)	P-value
Age (years)	78.5±.6	79.5±9.2	0.513	78.2±8.2	79.1±6.5	0.615
Male sex (%)	90.9	78.6	0.060	91.6	89.7	0.770
BMI (kg/m^2	20.9±3.8	20.4±3.3	0.502	21.2±3.1	20.5±4.6	0.403
SBP (mmHg)	123.0±19.5	129.5±27.3	0.207	122.5±16.8	123.5±17.7	0.863
HR (bpm, baseline)	80.0±11.9	86.0±18.1	0.183	75.9±13.3	84.1±10.5	0.048
HR (bpm, at 1 year)	70.4±10.1	85.0±14.1	0.023	70.6±9.7	70.3±10.3	0.909
IHD (%)	38.1	34.2	0.445	44.4	31.8	0.349
Hypertension (%)	62.3	52.6	0.348	60.0	66.7	0.617
AF (%)	43.3	58.8	0.152	42.5	44.1	0.857
CKD (%)	64.1	50.0	0.290	68.0	57.1	0.511
EF (%)	45.8±18.7	45.2±17.7	0.323	38.2±15.1	54.3±16.5	0.002
TRPG (mmHg)	38.0±21.5	36.4±11.9	0.835	32.2±15.2	43.9±27.6	0.485
BNP (pg/mL)	307.3±242	306.1±229	0.056	300.9±182	313.7±292	0.850
FEV1 (L, baseline)	1.61±0.57	1.53±0.61	0.694	1.70±0.56	1.52±0.58	0.344
GOLD 3,4 (%)	30.9	37.0	0.589	25.7	36.9	0.400
ACE-I or ARB (%)	70.3	67.6	0.562	80.6	60.0	0.099
Inhaled tiotropium (%)	35.9	37.8	0.659	29.7	42.1	0.364

Note: Values are presented as means ± SD, unless otherwise specified.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; HR, heart rate; IHD, ischemic heart disease; AF, atrial fibrillation; CKD, chronic kidney disease; EF, ejection fraction; TRPG, tricuspid regurgitation pressure gradient; BNP, brain natriuretic peptide; FEV₁, forced expiratory volume in 1 second; GOLD, global initiative for chronic obstructive lung disease; ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker.

Table 2 HRs for the risk of all-cause mortality

	Unadjusted HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
Age	0.99 (0.95–1.05)	0.978
Male sex	0.98 (0.23–4.28)	0.988
BMI	0.97 (0.85–1.10)	0.652	0.94 (0.78–1.12)	0.478
Hypertension	2.59 (0.90–7.46)	0.077	2.25 (0.82–6.21)	0.118
Atrial fibrillation	2.98 (0.94–9.39)	0.063	2.32 (0.78–6.89)	0.130
β-blockers	0.41 (0.17–0.99)	0.047	0.46 (0.19–1.11)	0.087
BNP (≥300 pg/mL)	0.74 (0.17–3.32)	0.696	0.71 (0.29–6.36)	0.708
EF (<40%)	1.59 (0.42–6.04)	0.479	1.66 (0.41–6.70)	0.472
ACE-I or ARB	0.56 (0.21–1.52)	0.255	0.57 (0.21–1.56)	0.277
GOLD 3,4	0.82 (0.35–1.92)	0.652	0.75 (0.31–1.80)	0.511
Past history of COPD exacerbation	1.59 (0.84–3.02)	0.158	1.82 (0.90–3.67)	0.093
Inhaled tiotropium	0.42 (0.15–1.15)	0.090	0.42 (0.15–1.18)	0.099

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; BNP, brain natriuretic peptide; EF, ejection fraction; ACE-I, angiotensin I converting enzyme inhibitor; ARB, angiotensin II receptor blocker; GOLD, global initiative for chronic obstructive lung disease; COPD, chronic obstructive pulmonary disease.

Figure 1 Cumulative incidence of all-cause death.

Note: During the mean follow-up period of 33.9 months, the mortality was higher in heart failure and COPD patients treated without vs with β-blockers (log-rank P=0.039).
Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 3 HRs for the risk of COPD or CHF exacerbation

	Unadjusted HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
Age	1.03 (0.97–1.09)	0.363
Male sex	0.76 (0.23–2.54)	0.660
BMI	0.95 (0.87–1.04)	0.249	0.89 (0.72–1.10)	0.092
Hypertension	2.05 (0.84–5.00)	0.114	1.47 (0.63–3.43)	0.379
Atrial fibrillation	0.90 (0.39–2.07)	0.809	0.83 (0.36–1.91)	0.656
Bisoprolol	0.38 (0.15–0.98)	0.046	0.47 (0.18–1.24)	0.126
BNP (≥300 pg/mL)	2.12 (0.76–5.82)	0.147	1.91 (0.69–5.30)	0.215
EF (<40%)	2.09 (0.79–5.52)	0.136	2.10 (0.79–5.54)	0.135
ACE-I or ARB	0.71 (0.25–2.02)	0.523	0.51 (0.20–1.30)	0.157
GOLD 3,4	0.75 (0.26–2.22)	0.607	0.62 (0.20–1.94)	0.414
Past history of COPD exacerbation	2.51 (1.27–4.97)	0.008	3.11 (1.47–6.61)	0.003
Inhaled tiotropium	0.94 (0.49–1.83)	0.863	0.99 (0.50–1.97)	0.974

Abbreviations: HR, hazard ratio; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; CI, confidence interval; BMI, body mass index; BNP, brain natriuretic peptide; EF, ejection fraction; ACE-I, angiotensin I converting enzyme inhibitor; ARB, angiotensin II receptor blocker; GOLD, global initiative for chronic obstructive lung disease.

Table 4 Changes of the factors associated with heart failure

Variables	Carvedilol		P-value	Bisoprolol		P-value
	Baseline	Follow-up		Baseline	Follow-up
SBP (mmHg)	122.5±16.8	120.3±10.7	0.652	123.5±17.7	121.4±11.4	0.698
Heart rate (bpm)	75.9±13.3	70.6±9.7	0.122	84.1±10.5	70.3±10.3	<0.05
Data
eGFR (mL/min/1.73 m^2)	54.5±21.1	49.6±23.3	0.533	56.8±13.2	51.1±14.4	0.364
BNP (pg/mL)	300.9±181.8	248.0±273.8	0.547	313.7±291.8	230.7±224.8	0.421
TTE
EF Simpson (%)	38.2±15.1	41.8±11.4	0.200	54.3±16.5	57.1±18.8	0.870
TRPG (mmHg)	32.2±15.2	30.2±7.3	0.437	43.9±27.6	41.6±12.7	0.756

Note: Values are presented as means ± SD, unless otherwise specified.

Abbreviations: SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; TTE, trans-thoracic echocardiogram; EF, ejection fraction; TRPG, tricuspid regurgitation pressure gradient.

Figure 2 Cumulative incidence of all-cause death and CHF/COPD exacerbation.

Note: No significant difference was observed between the carvedilol and bisoprolol groups (log-rank P=0.112).

Abbreviations: CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease.

Figure 3 Cumulative incidence of CHF or COPD exacerbation.

Note: The event rate was higher in patients treated with carvedilol compared with those with bisoprolol (log-rank P=0.033).
Abbreviations: CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease.