Cardiovascular morbidity and the use of inhaled bronchodilators

Figures & data

Table 1 Characteristics of cases (at first hospitalization) and controls

		SVT cases	Controls	MI cases	Controls	HF cases	Controls	Stroke cases	Controls
Number of subjects		2054	20501	3855	38490	5407	53929	4961	49487
Gender	Males	48.2		61.7		49.8		49.8
Age	mean	71.2		69.1		76.0		73.4
	25th , 75th percentile	64, 80		61, 79		70, 84		67, 82
Respiratory Co-morbidity
	Asthma	10.1	10.9	9.6	11.0	7.1	9.1	8.0	10.0
	COPD	27.1	26.3	29.5	25.6	41.7	28.9	31.5	27.9
	Asthma and COPD	10.5	9.1	10.8	9.5	13.3	10.1	9.4	10.0
	Bronchitis	52.3	53.7	50.1	53.9	37.9	52.1	51.1	52.2
Any Non-cardiac Co-morbidity		39.5	34.0	44.4	32.9	51.7	35.8	46.2	34.9
Drug dispensed within
	IB 60 Days	7.8	4.8	6.6	4.7	14.9	5.4	5.6	5.0
	1 Year	11.2	7.6	10.3	7.5	20.4	8.4	10.1	7.9
	BA 60 Days	13.2	9.3	13.1	9.4	24.4	10.1	10.5	9.8
	1 Year	22.4	17.2	21.1	16.8	34.3	17.6	19.3	17.4
	ICS 60 Days	7.2	6.4	7.9	6.2	12.0	6.9	6.1	6.7
	1 Year	13.5	11.3	14.0	11.6	18.7	12.0	11.6	11.7
Cardiac Drugs
	Antiarrhythmics	36.8	9.2	11.8	7.9	34.6	9.8	16.8	9.6
	Nitrates	31.0	16.1	30.1	13.7	40.7	16.6	25.0	16.4
	Antihypertensives	37.5	27.6	32.4	25.7	42.0	28.8	37.8	28.1
	Furosemide	33.9	17.3	23.8	14.5	65.0	18.8	27.8	18.2
	Betablockers	29.4	14.1	20.1	12.8	20.7	13.8	20.4	13.8
	Calcium Channel Blockers	16.5	7.6	12.4	6.6	15.2	7.7	11.3	7.4
	ACEI	37.1	21.9	30.2	20.5	52.4	21.6	34.9	21.9
	Anticholesterol	13.0	10.5	15.1	10.2	12.1	9.2	13.8	9.4
	Any	81.2	55.3	67.4	51.6	88.9	58.6	73.2	56.7

Table 2 Odds ratios for the first hospitalization due to SVT

			Univariate		Multivariate
			All respiratory drugs	Plus respiratory comorbidity	Plus other comorbidity	Plus cardiac drugs	Interaction with cardiac drugs p-value	No cardiac drugs	Cardiac drugs
60 Days	IB	1.68	1.48	1.49	1.49	1.38	0.011	2.38	1.24
		1.41, 2.00	1.19, 1.84	1.20, 1.86	1.20, 1.85	1.10, 1.72		1.51, 3.74	0.99, 1.55
	BA	1.48	1.40	1.40	1.37	1.31	>0.05
		1.29, 1.70	1.17, 1.67	1.16, 1.69	1.14, 1.64	1.09, 1.57
	CS	1.13	0.79	0.79	0.80	0.79	>0.05
		0.95, 1.35	0.64, 0.98	0.64, 0.98	0.65, 0.99	0.64, 0.99
1 year	IB	1.53	1.33	1.36	1.36	1.27	0.046	1.80	1.17
		1.32, 1.77	1.12, 1.59	1.13, 1.63	1.13, 1.63	1.06, 1.53		1.22, 2.65	0.97, 1.41
	BA	1.40	1.32	1.35	1.32	1.25	>0.05
		1.25, 1.56	1.14, 1.53	1.16, 1.57	1.14, 1.54	1.07, 1.46
	CS	1.23	0.93	0.96	0.96	0.93	>0.05
		1.07, 1.40	0.78, 1.09	0.80, 1.14	0.80, 1.14	0.78, 1.11

Table 5 Odds ratios for first hospitalization due to stroke

			Univariate		Multivariate
			All respiratory drugs	Plus respiratory comorbidity	Plus other comorbidity	Plus cardiac drugs	Interaction with cardiac drugs p-value	No cardiac drugs	Cardiac drugs
60 Days	IB	1.18	1.20	1.09	1.10	1.04	<0.001	1.46	0.96
		1.04, 1.33	1.03, 1.40	0.93, 1.27	0.94, 1.28	0.90, 1.22		1.05, 2.03	0.81, 1.14
	BA	1.08	1.11	1.05	1.05	1.01	<0.001	1.32	0.94
		0.98, 1.19	0.98, 1.26	0.92, 1.19	0.92, 1.19	0.90, 1.15		1.05, 1.67	0.81, 1.08
	CS	0.90	0.79	0.78	0.80	0.78	>0.05
		0.80, 1.02	0.68, 0.91	0.67, 0.90	0.69, 0.92	0.67, 0.90
1 year	IB	1.30	1.32	1.20	1.18	1.13	<0.001	1.44	1.06
		1.18, 1.44	1.17, 1.48	1.07, 1.36	1.05, 1.34	1.00, 1.27		1.11, 1.87	0.93, 1.21
	BA	1.13	1.12	1.08	1.06	1.01	<0.001	1.31	0.95
		1.05, 1.22	1.01, 1.24	0.97, 1.19	0.96, 1.17	0.92, 1.12		1.09, 1.57	0.85, 1.07
	CS	0.99	0.84	0.84	0.85	0.83	>0.05
		0.90, 1.08	0.75, 0.93	0.75, 0.94	0.76, 0.96	0.74, 0.94

Table 6 Significant interactions between respiratory drugs and cardiac drug classes associated with causes of hospitalization*

Respiratory drugs	Dispensed within	60 Days			365 Days
Cardiac drugs		Off	On	p value	Off	On	p value
SVT	IB and Antiarrhythmics	1.76	0.72	<0.0001	1.53	0.72	<0.0001
		1.36, 2.27	0.52, 0.99		1.24, 1.89	0.55, 0.94
	BA and Antiarrhythmics	1.32	0.77	0.0004	1.31	0.8	0.0001
		1.09, 1.61	0.60, 1.00		1.12, 1.52	0.65, 0.99
Myocardial infarction	BA and Nitrates				1.26	1.00	0.012
					1.13, 1.41	0.86, 1.17
Heart failure	IB and Furosemide	1.75	1.18	0.0002	1.73	1.26	0.0005
		1.45, 2.10	1.04, 1.34		1.48, 2.03	1.13, 1.40
	BA and Furosemide	2.22	1.45	<0.0001	1.68	1.28	0.0002
		1.94, 2.54	1.30, 1.61		1.50, 1.89	1.17, 1.41
	BA and ACEI	2.17	1.87	0.0417
		1.94, 2.43	1.66, 2.10
Stroke	IB and ACEI	1.26	0.88	0.006	1.33	1.01	0.01
		1.05, 1.50	0.70, 1.09		1.15, 1.54	0.86, 1.20
	BA and Antihypertensives	1.06	0.84	0.018	1.06	0.89	0.03
		0.93, 1.21	0.71, 0.99		0.95, 1.17	0.78, 1.01

* Shown are odds ratios relating bronchodilators (IB or BA) to hospitalization for cardiovascular disease when patients were using (On) and not using (Off) groups of cardiac drugs.

Table 4 Odds ratios for first hospitalization due to heart failure

			Univariate		Multivariate
			All respiratory drugs	Plus respiratory comorbidity	Plus other comorbidity	Plus cardiac drugs	Interaction with cardiac drugs p-value
60 Days	IB	3.07	1.80	1.59	1.59	1.47	>0.05
		2.82, 3.34	1.62, 2.00	1.43, 1.77	1.62, 1.78	1.31, 1.64
	BA	2.88	2.45	2.25	2.21	1.99	>0.05
		2.69, 3.08	2.23, 2.68	2.04, 2.47	2.00, 2.43	1.81, 2.20
	CS	1.84	0.82	0.83	0.87	0.85	>0.05
		1.69, 2.02	0.73, 0.91	0.74, 0.92	0.78, 0.97	0.76, 0.95
1 year	IB	2.80	1.90	1.69	1.68	1.55	>0.05
		2.60, 3.01	1.73, 2.08	1.54, 1.86	1.53, 1.85	1.41, 1.71
	BA	2.45	2.15	2.03	1.96	1.74	>0.05
		2.31, 2.61	1.98, 2.33	1.86, 2.21	1.79, 2.13	1.60, 1.91
	CS	1.69	0.78	0.82	0.84	0.82	>0.05
		1.57, 1.82	0.71, 0.86	0.74, 0.90	0.76, 0.93	0.75, 0.91

Table 3 Odds ratios for first hospitalization due to myocardial infarction

			Univariate		Multivariate
			All respiratory drugs	Plus respiratory comorbidity	Plus other comorbidity	Plus cardiac drugs	Interaction with cardiac drugs p-value
60 Days	IB	1.42	1.13	1.05	1.04	1.00	>0.05
		1.24, 1.63	0.96, 1.33	0.89, 1.23	0.88, 1.23	0.85, 1.18
	BA	1.46	1.39	1.35	1.33	1.31	>0.05
		1.32, 1.61	1.22, 1.59	1.18, 1.55	1.16, 1.53	1.15, 1.51
	CS	1.30	1.01	1.01	1.04	0.99	>0.05
		1.15, 1.48	0.87, 1.17	0.87, 1.18	0.89, 1.22	0.85, 1.16
1 year	IB	1.40	1.22	1.13	1.11	1.07	>0.05
		1.25, 1.57	1.07, 1.39	0.98, 1.29	0.97, 1.28	0.93, 1.23
	BA	1.33	1.24	1.22	1.18	1.15	>0.05
		1.22, 1.44	1.11, 1.39	1.08, 1.36	1.05, 1.32	1.02, 1.29
	CS	1.24	1.00	1.02	1.04	1.01	>0.05
		1.13, 1.37	0.89, 1.13	0.89, 1.16	0.91, 1.18	0.89, 1.15