Statins in High-Risk Chronic Obstructive Pulmonary Disease Outpatients: No Impact on Time to First Exacerbation and All-Cause Mortality – The STATUETTE Cohort Study

Figures & data

Figure 1 Schematic overview of study design and Mantel-Byar approach to immortal-time bias in a retrospective cohort of 950 COPD outpatients followed for 3.5 years.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 1 Demographics of 950 COPD Patients, Divided by Statin Treatment Status, at an University Hospital Outpatient Clinic

	Total, N = 950^a	Statin Users, N = 393^a	Non-Users, N = 557^a	p-value^b
Male (sex)	448 (47%)	207 (53%)	241 (43%)	0.005
Age	71 (11)	73 (9)	69 (11)	< 0.001
BMI	25.5 (5.8)	26.3 (5.5)	24.9 (5.9)	< 0.001
History of smoking				0.701
Current smoker	247 (26%)	101 (26%)	146 (26%)
Ex. smoker	665 (70%)	279 (71%)	386 (69%)
Never-smoker	37 (3.9%)	13 (3.3%)	24 (4.3%)
Missing values	1	1	0
Pack years of smoking	43 (30, 51)	45 (32, 55)	40 (30, 50)	< 0.001
Missing values	74	26	48
FEV1%pred	44 (33, 57)	45 (35, 60)	43 (31, 56)	0.015
Missing values	1	0	1
GOLD stage 1–4				0.137
GOLD 1	39 (4.1%)	19 (4.8%)	20 (3.6%)
GOLD 2	332 (35%)	149 (38%)	183 (33%)
GOLD 3	392 (41%)	162 (41%)	230 (41%)
GOLD 4	186 (20%)	63 (16%)	123 (22%)
MRC	3.30 (1.21)	3.33 (1.16)	3.28 (1.25)	0.633
Missing values	11	6	5
History of severe exacerbations (previously)	211 (22%)	89 (23%)	122 (22%)	0.848
GOLD A-D groups				0.626
A	219 (24%)	83 (22%)	136 (26%)
B	308 (34%)	134 (35%)	174 (33%)
C	57 (6.3%)	24 (6.3%)	33 (6.2%)
D	327 (36%)	138 (36%)	189 (36%)
Missing values	39	14	25
Comorbidities
Atrial fibrillation	157 (17%)	82 (21%)	75 (13%)	0.003
Hypertension	469 (49%)	266 (68%)	203 (36%)	<0.001
Stable ischemic heart disease	79 (8.3%)	67 (17%)	12 (2.2%)	<0.001
History of ACS	59 (6.2%)	49 (12%)	10 (1.8%)	<0.001
Diabetes type I or II	140 (15%)	110 (28%)	30 (5.4%)	<0.001
History of stroke	102 (11%)	77 (20%)	25 (4.5%)	<0.001
Congestive heart failure	76 (8.0%)	53 (13%)	23 (4.1%)	<0.001
Cancer (any type)	128 (13%)	56 (14%)	72 (13%)	0.623
Peripheral vascular disease	57 (6.0%)	44 (11%)	13 (2.3%)	<0.001
Osteoporosis	241 (25%)	101 (26%)	140 (25%)	0.903
Concomitant asthma	176 (19%)	58 (15%)	118 (21%)	0.015
Total cholesterol (mM)	4.62 (1.62)	4.98 (1.07)	4.23 (1.12)	<0.001
Missing values	196	32	164
Single bronchodilator (LABA or LAMA)	631 (66%)	377 (68%)	254 (65%)	0.362
Dual bronchodilators (LABA and LAMA)	260 (27%)	154 (28%)	106 (27%)	0.876
ICS	69 (7.3%)	41(7.4%)	28 (7.1%)	0.991

Notes: ^aStatistics presented: n (%); mean (SD); median (IQR). ^bStatistical tests performed: chi-square test of independence; Wilcoxon rank-sum test.

Abbreviations: LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroids; ACS, acute coronary syndrome; BMI, Body Mass Index, GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV1%pred, predicted forced expiratory volume in one second; MRC, Medical Research Council score.

Table 2 A Time-Varying Covariate Cox Proportional Hazard Regression for Association of Statin Use and Hazard Ratio (HR) for Time to First Exacerbation in 950 COPD High-Risk Outpatients

	Crude			Adjusted			Interaction CVD
	HR	95% CI	p-value	HR	95% CI	p-value	HR	95% CI	p-value
Statin use	1.10	0.92, 1.32	0.276	1.15	0.96, 1.39	0.135	1.13	0.87, 1.46	0.359
Age				1.02	1.01, 1.02	<0.001	1.02	~1.01, 1.03	<0.001
Sex
Male				1			1
Female				1.08	0.91, 1.30	0.365	1.09	0.91, 1.31	0.334
Congestive heart failure				1.04	0.76, 1.42	0.816	1.03	0.74, 1.42	0.875
BMI				0.98	0.97, ~1.00	0.0344	0.98	0.97, ~1.00	0.0309
GOLD 1–4 stage
GOLD 1				1			1
GOLD 2				3.73	1.49, 9.0	0.00411	3.71	1.51, 9.12	0.00429
GOLD 3				5.74	2.34, 14.00	<0.001	5.71	2.33, 14.0	<0.001
GOLD 4				9.85	4.00, 24.2	<0.001	9.81	3.98, 24.1	<0.001
LABA or LAMA				1.23	0.98, 1.54	0.0749	1.23	0.98, 1.55	0.0702
LABA and LAMA				0.97	0.76, 1.23	0.792	0.97	0.76, 1.24	0.824
ICS				1.134	0.95, 1.88	0.0973	1.34	0.95, 1.89	0.0959
Cardiovascular disease							1.06	0.76, 1.48	0.718
Statin use * Cardiovascular disease							0.99	0.63, 1.54	0.968

Note: The analysis was stratified for smoking status.

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease severity staging; LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroids.

Table 3 A Time-Varying Covariate Cox Proportional Hazard Regression for Association of Statin Use and Hazard Ratio (HR) for All-Cause Mortality in 950 COPD High-Risk Outpatients

	Crude			Adjusted			Interaction CVD
	HR	95% CI	p-value	HR	95% CI	p-value	HR	95% CI	p-value
Statin use	1.25	0.96, 1.64	0.102	1.05	0.75, 1.47	0.777	0.81	0.49, 1.33	0.402
Congestive heart failure				1.44	0.86, 2.40	0.163	1.31	0.79, 2.19	0.298
BMI				0.97	0.94, ~1.00	0.008	0.96	0.93, 0.99	0.0185
GOLD I–V stage
GOLD 1				1	1		1	1
GOLD 2				1.54	0.45, 5.33	0.490	1.45	0.42, 5.00	0.557
GOLD 3				2.31	0.68, 7.87	0.179	2.12	0.62, 7.23	0.227
GOLD 4				4.07	1.18, 14.1	0.0269	4.02	1.16, 13.9	0.0282
Cardiovascular disease							1.81	1.04, 3.14	0.0345
Statin use * Cardiovascular disease							1.03	0.49, 2.19	0.992

Note: The analysis was stratified for age, sex and smoking status.

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease severity staging.