No increase in CV events with long-acting bronchodilators in COPD

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.