Beta-Blockers in COPD: A Methodological Review of the Observational Studies

Figures & data

Table 1. Observational studies investigating the effects of beta-blockers in COPD on the risk of death or COPD exacerbation, affected by confounding bias.

Study	Year	Outcome event	Rate ratio (95% CI)
Gottlieb (13)	1998	Death	0.60 (0.57–0.63)
Chen (14)	2001	Death	0.89 (0.79–1.00)*
		Exacerbation	0.75 (0.59–0.96)*
Au (15)	2004	Death	0.57 (0.33–0.89)
		Exacerbation	0.65 (0.29–1.48)
van Gestel (16)	2008	Death (short-term)	0.37 (0.19–0.72)
		Death (long-term)	0.73 (0.60-–0.88)
Hawkins (17)	2009	Death	0.72 (0.61–0.86)*
Ekström (19)	2013	Death	1.19 (1.04–1.37)
Mentz (18)	2015	Death	0.49 (0.30–0.80)*
Bhatt (20)	2016	Death	0.85 (0.54–1.32)
		Exacerbation	0.73 (0.60–0.90)
Duffy (21)	2017	Exacerbation	0.85 (0.60–1.00)*
Coiro (22)	2017	Death	0.73 (0.60–0.90)

* Our calculation.

Table 2. Observational studies investigating the effects of beta-blockers in COPD on the risk of death or exacerbation, affected by immortal time bias.

Study	Year	Outcome event	Rate ratio (95% CI)
Sin (23)	2002	Death	0.78 (0.63–0.95)
Dransfield (24)	2002	Death	0.39 (0.14–0.99)
Olenchock (25)	2009	Death	0.52 (0.45–0.60)
Rutten (26)	2010	Death	0.68 (0.56–0.83)
		Exacerbation	0.71 (0.60–0.83)
Short (27)	2011	Death	0.78 (0.67–0.92)
Quint (28)	2013	Death	0.50 (0.36–0.69)

Figure 1. Illustration of immortal time bias in cohort studies: The immortal time between the diagnosis of COPD (cohort entry) and the first beta-blocker prescription is misclassified as “exposed to beta-blocker” when, in fact ,the patient is unexposed.

Figure 2. Forest plot of hazard and rate ratios of mortality associated with beta-blocker use in COPD from observational studies from Tables 1 and 2, and pooled estimates by a random effects approach, according to confounding and immortal time biases.

Figure 3. Forest plot of hazard and rate ratios of COPD exacerbation associated with beta-blocker use in COPD from observational studies from Tables 1 and 2, and pooled estimates by a random effects approach, according to confounding and immortal time biases.

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