A systematic review of the cardiovascular risk of inhaled anticholinergics in patients with COPD

Figures & data

Table 1 Publications evaluating the association between inhaled anticholinergics and adverse cardiovascular outcomes

Positive association between anticholinergics and adverse cardiovascular outcomes				Negative association between anticholinergic and adverse cardiovascular outcomes
Author	Year published	Study design	Drug evaluated	Author	Year published	Study design	Drug evaluated
Anthonisen^Citation9 (LHS)	2002	Prospective, randomized, placebo-controlled, double-blind	Ipratropium vs placebo	Oba^Citation8	2008	Meta-analysis	Re-analysis of Singh^Citation7 meta-analysis
				Tashkin^Citation16	2008	Prospective, randomized, placebo-controlled, double-blind	Tiotropium vs placebo
Wedzicha^Citation10 (INSPIRE)	2008	Prospective, randomized, double-blind	Tiotropium vs salmeterol/fluticasone	Kesten^Citation15	2006	Pooled safety analysis	Tiotropium vs placebo
Singh^Citation7	2008	Meta-analysis	Ipratropium or tiotropium vs placebo or LABA or LABA-ICS	Salpeter^Citation17	2006	Meta-analysis	Ipratropium or tiotropium vs LABA or LABA-ICS
Lee^Citation11	2008	Nested case control	Ipratropium vs LABA, ICS or theophylline	Rodrigo^Citation18	2007	Meta-analysis	Ipratropium or tiotropium vs LABA or LABA-ICS
Macie^Citation12	2008	Nested case control	Ipratropium vs LABA or ICS	de Luise^Citation19	2007	Observational cohort	Tiotropium
Guite^Citation13	1999	Observational cohort	Ipratropium vs LABA or ICS	Sin^Citation20	2000	Observational cohort	Ipratropium
Ringback^Citation14	2003	Observational cohort	Ipratropium vs LABA or ICS	Jara^Citation21	2007	Observational cohort	Tiotropium vs LABA

Abbreviations: LABA, long-acting beta-agonist; ICS, inhaled corticosteroid.

Table 2 Comparisons of randomized controlled trials of bronchodilators in patients with COPD

	INSPIRE^Citation10		UPLIFT^Citation16		TORCH^Citation25
	SFC	TIO	TIO	PLAC	SFC	S	F	PLAC
Enrolled	658	665	2987	3006	1523	1521	1534	1524
Withdrew	232 (35%)	279 (42%)	1099 (37%)	1358 (45%)	522 (34%)	561 (37%)	587 (38%)	673 (44%)
Duration	2 years		4 years		3 years
Age	64	65	64	64	65	65	65	65
% men	81	84	75	74	76	76	75	76
Post-bronch Fev1	39	39	47	47	44	44	44	44
Smokers	38	38	29	30	43	43	43	43
Smoking history (pack-year)	41.3	39.5	49	48	49	49	49	47
SGRQ	48.6	49.1	45.7	46.0	49	50	49	49
On ICS	48	51	62	62	47	45	47	51
All cause mortality	21 (3%)	38 (6%)	14.9%	16.5%	12.6%	13.5%	16.0%	15.2%
Cardiac death	9 (1%)	19 (3%)	26 (0.9%)	32 (1.1)	4%	3%	4%	5%
History of CV disease	9 (3%)	24 (8%)	NR	NR	NR	NR	NR	NR

Abbreviations: SFC, salmeterol plus fluticasone combination; TIO, tiotropium; PLAC, placebo; S, salmeterol; F, fluticasone; ICS, inhaled corticosteroids; SGRQ, St George’s Respiratory Questionnaire.

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