J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 17, Number 9, October 2025, pages 507-517

Evaluating the Effectiveness of Triple Therapy in Chronic Obstructive Pulmonary Disease Patients: An Asian Population-Based Survey

Figure 1. Study flowchart for the composite outcome. COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; ICSs: inhaled corticosteroids.

**Table 1.** Baseline Characteristics of Study Population
Variables	Triple therapy (n = 16,792)	LABA + LAMA (n = 4,205)	Total (n = 20,997)	P value
ACEI: angiotensin-converting enzyme inhibitor; ACOs: asthma-COPD overlap syndrome; ARB: angiotensin II receptor blockers; BZD: benzodiazepine; CCB: calcium channel blocker; GERD: gastroesophageal reflux disease; LABA: long-acting beta2-agonists; LAMA: long-acting muscarinic antagonists; NSAID: non-steroid anti-inflammatory drug; PPI: proton-pump inhibitor; SABA: short-acting beta-agonists; SAMA: short-acting muscarinic antagonist; SCC: systematic corticosteroid.
Age, years old, mean (SD)	67.19 (10.72)	65.77 (11.73)	66.06 (11.54)	< 0.0001
Age group				< 0.0001
< 65yeras old	7,905 (47.08)	1,764 (41.95)	9,669 (46.05)
≥ 65 years old	8,887 (52.92)	2,441 (58.05)	11,328 (53.95)
Gender, n (%)				< 0.0001
Male	9,877 (58.79)	3,100 (73.70)	12,977 (61.80)
Female	6,915 (41.21)	1,105 (26.30)	8,020 (38.20)
Geographic area, n (%)				0.4935
North	9,246 (55.06)	2,129 (50.63)	11,375 (54.17)
Middle	2,656 (15.82)	741 (17.62)	3,397 (16.18)
South	4,513 (26.88)	1,184 (28.16)	5,697 (27.13)
East	377 (2.24)	151 (3.59)	528 (2.52)
COPD exacerbation (moderate or severe)				0.7758
0	13,213 (78.70)	3,325 (79.12)	16,538 (78.78)
1	1,625 (9.74)	392 (9.28)	2,017 (9.61)
≥ 2	1,954 (11.56)	488 (11.60)	24,42 (11.61)
Disease duration	207.8 (277.3)	183.9 (266)	203.1 (275.3)	< 0.0001
Urbanization, n (%)				0.023
Urban	9,583 (57.07)	2,303 (54.77)	11,886 (56.60)
Suburban	5,257 (31.31)	1,348 (32.06)	6,605 (31.46)
Rural	1,870 (11.13)	527 (12.53)	2,397 (11.42)
Unknown	82 (0.49)	27 (0.64)	109 (0.52)
Insurance premium, n (%)				0.4935
Less than minimum monthly wage	4,161 (24.77)	1,064 (25.30)	5,225 (24.88)
More than minimum monthly wage	12,631 (75.23)	3,141 (74.70)	15,772 (75.12)
Comorbidity, n (%)
Hypertension	5,348 (31.80)	1,504 (35.80)	6,852 (32.63)	< 0.0001
Atrial fibrillation	925 (5.50)	242 (5.80)	1,167 (5.56)	0.5327
Ischemic stroke	884 (5.26)	243 (5.78)	1,127 (5.37)	0.1856
Hemorrhagic stroke	93 (0.55)	28 (0.67)	121 (0.58)	0.3907
Heart failure	1,045 (6.22)	297 (7.06)	1,342 (6.39)	0.0465
Dyslipidemia	2,730 (16.25)	743 (17.67)	3,473 (16.54)	0.0276
Cardiac arrhythmia	1,144 (6.81)	334 (7.84)	1,478 (7.04)	0.0104
Peripheral vascular disease	121 (0.72)	31 (0.74)	152 (0.72)	0.9094
Rheumatic heart disease	143 (0.85)	35 (0.83)	178 (0.85)	0.9031
ACOs	2,248 (13.39)	267 (6.35)	2,515(11.98)	< 0.0001
Pneumonia	2,237 (13.32)	645 (15.34)	2,882 (13.73)	0.0007
Acute bronchitis	2,647 (15.76)	689 (16.4)	3,336 (15.89)	0.324
Influenza	335 (1.99)	89 (2.12)	424 (2.02)	0.6163
Dementia	371 (2.21)	100 (2.38)	471 (2.24)	0.5088
Depression	605 (3.60)	123 (2.93)	728 (4.37)	0.0317
Parkinsonism	241 (1.44)	50 (1.19)	291 (1.39)	0.2221
Diabetes mellitus	2,394 (14.26)	674 (16.03)	3,068 (14.61)	0.0036
Chronic kidney disease	651 (3.88)	180 (4.28)	831 (3.96)	0.2298
Chronic liver disease	625 (3.72)	167 (3.97)	792 (3.77)	0.4477
Coronary artery disease	2,040 (12.15)	612 (14.55)	2,652 (12.63)	< 0.0001
GERD	2,222 (13.23)	434 (10.32)	2,656 (12.65)	< 0.0001
Malignancy	2,021 (12.04)	525 (12.49)	2,546 (12.13)	0.4244
Sepsis	371 (2.21)	105 (2.50)	476 (2.27)	0.2624
Co-medication, n (%)
Antiplatelet agents	262 (1.56)	78 (1.85)	340 (1.62)	0.1758
Anticoagulants	4,900 (29.18)	1,128 (26.83)	6,028 (28.71)	0.0025
Lipid-lowering drugs	219 (1.30)	70 (1.66)	289 (1.38)	0.0728
PPI	729 (4.34)	152 (3.61)	881 (4.20)	0.0356
H₂-blocker	220 (1.31)	53 (1.26)	273 (1.30)	0.799
BZD drugs or Z-drugs	133 (0.79)	45 (1.07)	178 (0.85)	0.0786
Antipsychotics	635 (3.78)	143 (3.40)	778 (3.71)	0.2423
Opioids	1,629 (9.70)	377 (8.97)	2,006 (9.55)	0.1468
Systematic corticosteroids	395 (2.35)	95 (2.26)	490 (2.33)	0.7206
NSAID	206 (1.23)	44 (1.05)	250 (1.19)	0.3348
CCB	267 (1.59)	92 (2.19)	359 (1.71)	0.0075
Diuretics	621 (3.70)	162 (3.85)	783 (3.73)	0.6366
ACEI	2,798 (16.66)	667 (15.86)	3,465 (16.50)	0.211
ARB	352 (2.09)	110 (2.62)	20,535 (97.8)	0.0399
Beta-blocker	408 (2.43)	80 (1.90)	488 (2.32)	0.0086
Digoxin	25 (0.15)	7 (0.17)	32 (0.15)	0.7937
Antiarrhythmics	3,123 (18.60)	758 (18.03)	3,881 (18.48)	0.3928
Nitrates	1,567 (9.23)	368 (8.75)	1,935 (9.22)	0.2353
Influenza vaccine	1,635 (9.74)	465 (11.06)	2,100 (10.00)	0.0106
Pneumococcal vaccine	3,196 (19.03)	882 (20.98)	4,078 (19.42)	0.0044

Table 1. Baseline Characteristics of Study Population

Variables

Triple therapy (n = 16,792)

LABA + LAMA (n = 4,205)

Total (n = 20,997)

P value

ACEI: angiotensin-converting enzyme inhibitor; ACOs: asthma-COPD overlap syndrome; ARB: angiotensin II receptor blockers; BZD: benzodiazepine; CCB: calcium channel blocker; GERD: gastroesophageal reflux disease; LABA: long-acting beta2-agonists; LAMA: long-acting muscarinic antagonists; NSAID: non-steroid anti-inflammatory drug; PPI: proton-pump inhibitor; SABA: short-acting beta-agonists; SAMA: short-acting muscarinic antagonist; SCC: systematic corticosteroid.

Age, years old, mean (SD)

67.19 (10.72)

65.77 (11.73)

66.06 (11.54)

< 0.0001

Age group

< 0.0001

< 65yeras old

7,905 (47.08)

1,764 (41.95)

9,669 (46.05)

≥ 65 years old

8,887 (52.92)

2,441 (58.05)

11,328 (53.95)

Gender, n (%)

< 0.0001

Male

9,877 (58.79)

3,100 (73.70)

12,977 (61.80)

Female

6,915 (41.21)

1,105 (26.30)

8,020 (38.20)

Geographic area, n (%)

0.4935

North

9,246 (55.06)

2,129 (50.63)

11,375 (54.17)

Middle

2,656 (15.82)

741 (17.62)

3,397 (16.18)

South

4,513 (26.88)

1,184 (28.16)

5,697 (27.13)

East

377 (2.24)

151 (3.59)

528 (2.52)

COPD exacerbation (moderate or severe)

0.7758

13,213 (78.70)

3,325 (79.12)

16,538 (78.78)

1,625 (9.74)

392 (9.28)

2,017 (9.61)

≥ 2

1,954 (11.56)

488 (11.60)

24,42 (11.61)

Disease duration

207.8 (277.3)

183.9 (266)

203.1 (275.3)

< 0.0001

Urbanization, n (%)

0.023

Urban

9,583 (57.07)

2,303 (54.77)

11,886 (56.60)

Suburban

5,257 (31.31)

1,348 (32.06)

6,605 (31.46)

Rural

1,870 (11.13)

527 (12.53)

2,397 (11.42)

Unknown

82 (0.49)

27 (0.64)

109 (0.52)

Insurance premium, n (%)

0.4935

Less than minimum monthly wage

4,161 (24.77)

1,064 (25.30)

5,225 (24.88)

More than minimum monthly wage

12,631 (75.23)

3,141 (74.70)

15,772 (75.12)

Comorbidity, n (%)

Hypertension

5,348 (31.80)

1,504 (35.80)

6,852 (32.63)

< 0.0001

Atrial fibrillation

925 (5.50)

242 (5.80)

1,167 (5.56)

0.5327

Ischemic stroke

884 (5.26)

243 (5.78)

1,127 (5.37)

0.1856

Hemorrhagic stroke

93 (0.55)

28 (0.67)

121 (0.58)

0.3907

Heart failure

1,045 (6.22)

297 (7.06)

1,342 (6.39)

0.0465

Dyslipidemia

2,730 (16.25)

743 (17.67)

3,473 (16.54)

0.0276

Cardiac arrhythmia

1,144 (6.81)

334 (7.84)

1,478 (7.04)

0.0104

Peripheral vascular disease

121 (0.72)

31 (0.74)

152 (0.72)

0.9094

Rheumatic heart disease

143 (0.85)

35 (0.83)

178 (0.85)

0.9031

ACOs

2,248 (13.39)

267 (6.35)

2,515(11.98)

< 0.0001

Pneumonia

2,237 (13.32)

645 (15.34)

2,882 (13.73)

0.0007

Acute bronchitis

2,647 (15.76)

689 (16.4)

3,336 (15.89)

0.324

Influenza

335 (1.99)

89 (2.12)

424 (2.02)

0.6163

Dementia

371 (2.21)

100 (2.38)

471 (2.24)

0.5088

Depression

605 (3.60)

123 (2.93)

728 (4.37)

0.0317

Parkinsonism

241 (1.44)

50 (1.19)

291 (1.39)

0.2221

Diabetes mellitus

2,394 (14.26)

674 (16.03)

3,068 (14.61)

0.0036

Chronic kidney disease

651 (3.88)

180 (4.28)

831 (3.96)

0.2298

Chronic liver disease

625 (3.72)

167 (3.97)

792 (3.77)

0.4477

Coronary artery disease

2,040 (12.15)

612 (14.55)

2,652 (12.63)

< 0.0001

GERD

2,222 (13.23)

434 (10.32)

2,656 (12.65)

< 0.0001

Malignancy

2,021 (12.04)

525 (12.49)

2,546 (12.13)

0.4244

Sepsis

371 (2.21)

105 (2.50)

476 (2.27)

0.2624

Co-medication, n (%)

Antiplatelet agents

262 (1.56)

78 (1.85)

340 (1.62)

0.1758

Anticoagulants

4,900 (29.18)

1,128 (26.83)

6,028 (28.71)

0.0025

Lipid-lowering drugs

219 (1.30)

70 (1.66)

289 (1.38)

0.0728

PPI

729 (4.34)

152 (3.61)

881 (4.20)

0.0356

H₂-blocker

220 (1.31)

53 (1.26)

273 (1.30)

0.799

BZD drugs or Z-drugs

133 (0.79)

45 (1.07)

178 (0.85)

0.0786

Antipsychotics

635 (3.78)

143 (3.40)

778 (3.71)

0.2423

Opioids

1,629 (9.70)

377 (8.97)

2,006 (9.55)

0.1468

Systematic corticosteroids

395 (2.35)

95 (2.26)

490 (2.33)

0.7206

NSAID

206 (1.23)

44 (1.05)

250 (1.19)

0.3348

CCB

267 (1.59)

92 (2.19)

359 (1.71)

0.0075

Diuretics

621 (3.70)

162 (3.85)

783 (3.73)

0.6366

ACEI

2,798 (16.66)

667 (15.86)

3,465 (16.50)

0.211

ARB

352 (2.09)

110 (2.62)

20,535 (97.8)

0.0399

Beta-blocker

408 (2.43)

80 (1.90)

488 (2.32)

0.0086

Digoxin

25 (0.15)

7 (0.17)

32 (0.15)

0.7937

Antiarrhythmics

3,123 (18.60)

758 (18.03)

3,881 (18.48)

0.3928

Nitrates

1,567 (9.23)

368 (8.75)

1,935 (9.22)

0.2353

Influenza vaccine

1,635 (9.74)

465 (11.06)

2,100 (10.00)

0.0106

Pneumococcal vaccine

3,196 (19.03)

882 (20.98)

4,078 (19.42)

0.0044

**Table 2.** The Study Outcomes of Counting Cox Model
	Observation period (days)	Event number	Crude HR (95% CI)	Adjusted HR (95% CI)
COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; HR: hazard ratio; CI: confidence interval.
Primary outcomes
Primary outcome 1
LABA + LAMA	2,490,676	1,534	1 (reference)
Triple therapy	7,355,285	5,105	1.081 (1.020 - 1.145)	1.162 (1.098 - 1.230)
Primary outcome 2
LABA + LAMA	2,490,676	1,475	1 (reference)
Triple therapy	7,355,285	4,982	1.097 (1.034 - 1.164)	1.171 (1.105 - 1.241)
Secondary outcomes
All-cause mortality
LABA + LAMA	3,676,382	779	1 (reference)
Triple therapy	10,547,405	1,902	0.842 (0.779 - 0.910)	1.074 (0.994 - 1.161)
Respiratory-related mortality
LABA + LAMA	3,676,405	524	1 (reference)
Triple therapy	10,547,405	1,292	0.846 (0.770 - 0.930)	1.089 (0.991 - 1.196)
Moderate COPD exacerbation
LABA + LAMA	3,146,834	494	1 (reference)
Triple therapy	9,247,962	1,688	1.033 (0.934 - 1.143)	1.027 (0.931 - 1.134)
Sever COPD exacerbation
LABA + LAMA	3,572,160	88	1 (reference)
Triple therapy	10,221,161	445	1.335 (1.059 - 1.683)	1.346 (1.078 - 1.682)
Acute respiratory failure
LABA + LAMA	3,628,098	95	1 (reference)
Triple therapy	10,425,265	323	1.132 (1.061 - 1.207)	1.315 (1.047 - 1.653)
Pneumonia
LABA + LAMA	3,325,536	539	1 (reference)
Triple therapy	9,563,094	1,715	1.149 (1.043 - 1.266)	1.221 (1.109 - 1.344)
Respiratory-related admission
LABA + LAMA	2,748,346	614	1 (reference)
Triple therapy	7,986,776	2,163	1.189 (1.087 - 1.301)	1.264 (1.157 - 1.382)

Table 2. The Study Outcomes of Counting Cox Model

Observation period (days)

Event number

Crude HR (95% CI)

Adjusted HR (95% CI)

COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; HR: hazard ratio; CI: confidence interval.

Primary outcomes

Primary outcome 1

LABA + LAMA

2,490,676

1,534

1 (reference)

Triple therapy

7,355,285

5,105

1.081 (1.020 - 1.145)

1.162 (1.098 - 1.230)

Primary outcome 2

LABA + LAMA

2,490,676

1,475

1 (reference)

Triple therapy

7,355,285

4,982

1.097 (1.034 - 1.164)

1.171 (1.105 - 1.241)

Secondary outcomes

All-cause mortality

LABA + LAMA

3,676,382

779

1 (reference)

Triple therapy

10,547,405

1,902

0.842 (0.779 - 0.910)

1.074 (0.994 - 1.161)

Respiratory-related mortality

LABA + LAMA

3,676,405

524

1 (reference)

Triple therapy

10,547,405

1,292

0.846 (0.770 - 0.930)

1.089 (0.991 - 1.196)

Moderate COPD exacerbation

LABA + LAMA

3,146,834

494

1 (reference)

Triple therapy

9,247,962

1,688

1.033 (0.934 - 1.143)

1.027 (0.931 - 1.134)

Sever COPD exacerbation

LABA + LAMA

3,572,160

1 (reference)

Triple therapy

10,221,161

445

1.335 (1.059 - 1.683)

1.346 (1.078 - 1.682)

Acute respiratory failure

LABA + LAMA

3,628,098

1 (reference)

Triple therapy

10,425,265

323

1.132 (1.061 - 1.207)

1.315 (1.047 - 1.653)

Pneumonia

LABA + LAMA

3,325,536

539

1 (reference)

Triple therapy

9,563,094

1,715

1.149 (1.043 - 1.266)

1.221 (1.109 - 1.344)

Respiratory-related admission

LABA + LAMA

2,748,346

614

1 (reference)

Triple therapy

7,986,776

2,163

1.189 (1.087 - 1.301)

1.264 (1.157 - 1.382)

**Table 3.** The Study Outcomes of Conventional Cox Model
	Observation period (days)	Event number	Crude HR (95% CI)	Adjusted HR (95% CI)
The multivariable models were adjusted for baseline characteristics, comorbidities, and concomitant medications. COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; HR: hazard ratio; CI: confidence interval.
Primary outcomes
Primary outcome 1
LABA + LAMA	2,490,676	1,534	1 (reference)
Triple therapy	7,355,285	5,105	0.978 (0.930 - 1.030)	1.004 (0.954 - 1.056)
Primary outcome 2
LABA + LAMA	2,490,676	1,475	1 (reference)
Triple therapy	7,355,285	4,982	0.988 (0.938 - 1.041)	1.013 (0.961 - 1.067)
Secondary outcomes
All-cause mortality
LABA + LAMA	3,676,382	779	1 (reference)
Triple therapy	10,547,405	1,902	0.989 (0.916 - 1.068)	1.110 (1.011 - 1.219)
Respiratory-related mortality
LABA + LAMA	3,676,405	524	1 (reference)
Triple therapy	10,547,405	1,292	1.032 (0.936 - 1.137)	1.179 (1.046 - 1.329)
Moderate COPD exacerbation
LABA + LAMA	3,146,834	494	1 (reference)
Triple therapy	9,247,962	1,688	1.159 (1.058 - 1.271)	1.134 (1.034 - 1.244)
Sever COPD exacerbation
LABA + LAMA	3,572,160	88	1 (reference)
Triple therapy	10,221,161	445	0.333 (0.300 - 0.371)	0.323 (0.291 - 0.361)
Acute respiratory failure
LABA + LAMA	3,628,098	95	1 (reference)
Triple therapy	10,425,265	323	1.313 (1.041 - 1.658)	1.406 (1.112 - 1.780)
Pneumonia
LABA + LAMA	3,325,536	539	1 (reference)
Triple therapy	9,563,094	1,715	1.007 (0.919 - 1.105)	1.040 (0.948 - 1.141)
Respiratory-related admission
LABA + LAMA	2,748,346	614	1 (reference)
Triple therapy	7,986,776	2,163	1.168 (1.072 - 1.273)	1.200 (1.101 - 1.308)

Table 3. The Study Outcomes of Conventional Cox Model

Observation period (days)

Event number

Crude HR (95% CI)

Adjusted HR (95% CI)

The multivariable models were adjusted for baseline characteristics, comorbidities, and concomitant medications. COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; HR: hazard ratio; CI: confidence interval.

Primary outcomes

Primary outcome 1

LABA + LAMA

2,490,676

1,534

1 (reference)

Triple therapy

7,355,285

5,105

0.978 (0.930 - 1.030)

1.004 (0.954 - 1.056)

Primary outcome 2

LABA + LAMA

2,490,676

1,475

1 (reference)

Triple therapy

7,355,285

4,982

0.988 (0.938 - 1.041)

1.013 (0.961 - 1.067)

Secondary outcomes

All-cause mortality

LABA + LAMA

3,676,382

779

1 (reference)

Triple therapy

10,547,405

1,902

0.989 (0.916 - 1.068)

1.110 (1.011 - 1.219)

Respiratory-related mortality

LABA + LAMA

3,676,405

524

1 (reference)

Triple therapy

10,547,405

1,292

1.032 (0.936 - 1.137)

1.179 (1.046 - 1.329)

Moderate COPD exacerbation

LABA + LAMA

3,146,834

494

1 (reference)

Triple therapy

9,247,962

1,688

1.159 (1.058 - 1.271)

1.134 (1.034 - 1.244)

Sever COPD exacerbation

LABA + LAMA

3,572,160

1 (reference)

Triple therapy

10,221,161

445

0.333 (0.300 - 0.371)

0.323 (0.291 - 0.361)

Acute respiratory failure

LABA + LAMA

3,628,098

1 (reference)

Triple therapy

10,425,265

323

1.313 (1.041 - 1.658)

1.406 (1.112 - 1.780)

Pneumonia

LABA + LAMA

3,325,536

539

1 (reference)

Triple therapy

9,563,094

1,715

1.007 (0.919 - 1.105)

1.040 (0.948 - 1.141)

Respiratory-related admission

LABA + LAMA

2,748,346

614

1 (reference)

Triple therapy

7,986,776

2,163

1.168 (1.072 - 1.273)

1.200 (1.101 - 1.308)

**Table 4.** Sensitivity Analysis of Population Excluding Asthma-COPD Overlap Patients
	Observation period (days)	Event number	Crude HR (95% CI)	Adjusted HR (95% CI)
The multivariable models were adjusted for baseline characteristics, comorbidities, and concomitant medications. COPD: chronic obstructive pulmonary disease; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; HR: hazard ratio; CI: confidence interval.
Primary outcomes
Primary outcome 1
LABA + LAMA	2,442,682	1,490	1 (reference)
Triple therapy	6,333,410	4,473	1.117 (1.053 - 1.185)	1.174 (1.107 - 1.246)
Primary outcome 2
LABA + LAMA	2,442,682	1,434	1 (reference)
Triple therapy	6,333,410	4,359	1.130 (1.064 - 1.200)	1.187 (1.117 - 1.261)
Secondary outcomes
All-cause mortality
LABA + LAMA	3,616,963	868	1 (reference)
Triple therapy	9,158,924	1,988	0.905 (0.835 - 0.980)	1.017 (0.938 - 1.102)
Respiratory-related mortality
LABA + LAMA	3,616,986	590	1 (reference)
Triple therapy	9,158,924	1,352	0.902 (0.819 - 0.994)	1.027 (0.932 - 1.132)
Moderate COPD exacerbation
LABA + LAMA	3,068,886	491	1 (reference)
Triple therapy	7,999,751	1,493	1.031 (0.930 - 1.143)	1.064 (0.959 - 1.180)
Sever COPD exacerbation
LABA + LAMA	3,521,047	89	1 (reference)
Triple therapy	8,863,890	387	1.312 (1.039 - 1.657)	1.370 (1.084 - 1.732)
Acute respiratory failure
LABA + LAMA	3,201,942	81	1 (reference)
Triple therapy	8,157,867	259	1.227 (0.955 - 1.577)	1.375 (1.066 - 1.772)
Pneumonia
LABA + LAMA	3,303,350	492	1 (reference)
Triple therapy	8,449,309	1,283	1.064 (0.959 - 1.181)	1.162 (1.046 - 1.291)
Respiratory-related admission
LABA + LAMA	3,201,942	569	1 (reference)
Triple therapy	8,157,867	1,681	1.122 (1.020 - 1.235)	1.216 (1.104 - 1.338)

Table 4. Sensitivity Analysis of Population Excluding Asthma-COPD Overlap Patients

Observation period (days)

Event number

Crude HR (95% CI)

Adjusted HR (95% CI)

Primary outcomes

Primary outcome 1

LABA + LAMA

2,442,682

1,490

1 (reference)

Triple therapy

6,333,410

4,473

1.117 (1.053 - 1.185)

1.174 (1.107 - 1.246)

Primary outcome 2

LABA + LAMA

2,442,682

1,434

1 (reference)

Triple therapy

6,333,410

4,359

1.130 (1.064 - 1.200)

1.187 (1.117 - 1.261)

Secondary outcomes

All-cause mortality

LABA + LAMA

3,616,963

868

1 (reference)

Triple therapy

9,158,924

1,988

0.905 (0.835 - 0.980)

1.017 (0.938 - 1.102)

Respiratory-related mortality

LABA + LAMA

3,616,986

590

1 (reference)

Triple therapy

9,158,924

1,352

0.902 (0.819 - 0.994)

1.027 (0.932 - 1.132)

Moderate COPD exacerbation

LABA + LAMA

3,068,886

491

1 (reference)

Triple therapy

7,999,751

1,493

1.031 (0.930 - 1.143)

1.064 (0.959 - 1.180)

Sever COPD exacerbation

LABA + LAMA

3,521,047

1 (reference)

Triple therapy

8,863,890

387

1.312 (1.039 - 1.657)

1.370 (1.084 - 1.732)

Acute respiratory failure

LABA + LAMA

3,201,942

1 (reference)

Triple therapy

8,157,867

259

1.227 (0.955 - 1.577)

1.375 (1.066 - 1.772)

Pneumonia

LABA + LAMA

3,303,350

492

1 (reference)

Triple therapy

8,449,309

1,283

1.064 (0.959 - 1.181)

1.162 (1.046 - 1.291)

Respiratory-related admission

LABA + LAMA

3,201,942

569

1 (reference)

Triple therapy

8,157,867

1,681

1.122 (1.020 - 1.235)

1.216 (1.104 - 1.338)