Impact of selective and nonselective beta-blockers on the risk of severe exacerbations in patients with COPD

Figures & data

Table 1 Characteristics of severe AE cases and their matched controls selected from a cohort of patients with COPD

Characteristics	Controls	Cases
	n=55,970	n=16,067
Male, n (%)	42,750 (76.4)	11,978 (74.6)
Age, mean ± SD	72.12±8.25	72.50±9.01
Days from COPD diagnosis to drug date, mean ± SD	662.10±820.68	753.42±890.29
One year before the event date
Exacerbation,a n (%)	21,631 (38.6)	8,200 (51.0)
Hospitalization for COPD, n (%)	8,050 (14.4)	4,266 (26.6)
Emergency department visits, n (%)	4,271 (7.6)	2,618 (16.3)
Oral steroids, n (%)	9,039 (16.1)	4,146 (25.8)
Antibiotics, n (%)	5,864 (10.5)	2,482 (15.4)
Comorbidity
Osteoporosis, n (%)	4,153 (7.4)	1,327 (8.3)
DM, n (%)	11,893 (21.2)	4,001 (24.9)
Cancer, n (%)	5,531 (9.9)	2,275 (14.2)
Asthma, n (%)	21,257 (38.0)	8,063 (50.2)
Depression, n (%)	1,098 (2.0)	350 (2.2)
Anxiety	12,467 (22.3)	3,664 (22.8)
Dyslipidemia, n (%)	54 (22.0)	3,077 (19.2)
Chronic liver disease, n (%)	7,198 (12.9)	2,165 (13.5)
Renal failure, n (%)	5,198 (9.3)	2,011 (12.5)
Hypertension, n (%)	39,620 (70.8)	11,299 (70.3)
Heart failure, n (%)	7,023 (12.5)	3,347 (20.8)
Cardiac arrhythmia, n (%)	10,298 (18.4)	3,557 (22.1)
AMI, n (%)	778 (1.4)	409 (2.5)
Stroke, n (%)	9,137 (16.3)	3,114 (19.4)
Ischemic heart disease, n (%)	20,685 (37.0)	6,523 (40.6)
CCI (mean ± SD)	2.15±1.65	2.73±1.98

Note:

a Exacerbation includes use of antibiotics and oral steroids, emergency visits, and hospitalization for COPD.

Abbreviations: AE, adverse event; AMI, acute mycardial infarction; CCI, Charlson comorbidity index; DM, diabetes mellitus.

Table 2 Crude and adjusted rate ratios of severe AE associated with current use, dose, and past use of beta-blockers

Use of beta-blocker	Cases	Controls	Crude OR	95% CI	Adjusteda OR	95% CI
Selective beta-blockers
Number of subjects	16,067	55,970
No use,b n (%)	12,022 (74.8)	39,483 (70.5)	1.00		1.00	Reference
Current use,c n (%)	2,212 (13.8)	9,860 (17.6)	0.76	0.72–0.80	0.90	0.85–0.96
Past use,d n (%)	1,833 (11.4)	6,627 (11.8)	0.95	0.90–1.01	0.98	0.92–1.04
Nonselective beta-blockers
Number of subjects	16,067	55,970
No use,b n (%)	8,402 (52.3)	31,705 (56.6)	1.00		1.00	Reference
Current use,c n (%)	4,316 (26.9)	12,878 (23.0)	1.35	1.29–1.42	1.21	1.14–1.27
Past use,d n (%)	3,349 (20.8)	11,387 (20.3)	1.14	1.08–1.20	1.03	0.98–1.09

Notes:

a Adjusted for age, living region, income, occupation, calendar year, antibiotics and oral steroids use, number of hospitalization and emergency visits for COPD, days from COPD diagnosis to beta-blockers use, and comorbidities (including osteoporosis, DM, cancer, and asthma).

b No use in recent year.

c At least one prescription in the 60 days before the event date.

d At least one prescription in the year before the event date, but no prescription in the 60 days before the event date.

Abbreviations: AE, adverse event; OR, odds ratio; CI, confidence interval; DM, diabetes mellitus.

Table 3 Risk of severe AE associated with any current use of selective/nonselective beta-blockers in patients with COPD

Drug type	Cases	Controls	Crude OR	95% CI	Adjusteda OR	95% CI
Selective
Acebutolol	150	804	0.71	0.59–0.84	0.85	0.71–1.02
Atenolol	1,568	6,804	0.82	0.77–0.87	0.97	0.91–1.03
Betaxolol	92	542	0.63	0.50–0.78	0.75	0.60–0.95
Bisoprolol	195	768	0.77	0.66–0.91	0.85	0.71–1.01
Metoprolol	183	795	0.81	0.69–0.96	0.88	0.74–1.04
Nonselective
Alprenolol	13	66	0.69	0.38–1.27	0.70	0.38–1.30
Carteolol	28	100	1.05	0.69–1.60	1.02	0.65–1.61
Carvedilol	753	2,397	1.08	0.99–1.17	0.97	0.88–1.06
Labetalol	525	1,167	1.62	1.46–1.81	1.49	1.32–1.67
Nadolol	45	149	1.12	0.80–1.57	1.17	0.82–1.66
Pindolol	5	42	0.41	0.16–1.05	0.39	0.15–1.01
Propranolol	3,031	9,131	1.24	1.18–1.31	1.16	1.10–1.23
Sotalol	4	30	0.49	0.17–1.40	0.57	0.19–1.71

Note:

a Adjusted for age, living region, income, occupation, calendar year, antibiotics and oral steroids use, number of hospitalization and emergency visits for COPD, days from COPD diagnosis to beta-blockers use, and comorbidities.

Abbreviations: AE, adverse event; OR, odds ratio; CI, confidence interval.

Figure 1 Subgroup analysis of COPD severe exacerbation among (A) nonselective and (B) selective beta-blockers.

Figure S1 Study flow chart.

Figure S2 Occurrence of severe acute exacerbation vs mean daily dose (DDD) of (A) nonselective and (B) selective beta-blockers.

Abbreviation: DDD, defined daily dose.

Figure S3 Occurrence of severe acute exacerbation vs duration (days) of (A) nonselective and (B) selective beta-blockers.