Alisha Skinner, MD

Background: Long-acting inhaled bronchodilator use (LABA or LAMA) in patients with COPD is the mainstay of treatment. Prior studies have reported a possible interaction between LABA or LAMA use and increased rates of cardiovascular events; however, the results have been variable. The findings have been confounded by incomplete medical records, exclusion of patients with CVD in bronchodilator trials, and high patient drop out rates. This study aims to assess the association between LABA or LAMA use in patients with COPD and the risk of CVD.

Study design: Nested case control study.

Setting: Taiwanese national database.

Synopsis: This study included 284,200 LABA and LAMA naive patients who were aged 40 years or older and had COPD (mean age, 71.4 years); it retrieved health care claims data from 2007 through 2011 for these patients from the Taiwan National Health Insurance Research Database. During a mean follow-up of 2.0 years, 37,719 patients experienced a cardiovascular event, and 146,139 matched controls were identified. LABA or LAMA use was measured in the year preceding the cardiovascular event and stratified by duration since initiation of LABA or LAMA treatment. Logistical regression was performed to estimate the odds ratios of CVD from LABA and LAMA treatment. New LABA use was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) increased cardiovascular risk within 30 days of initiation, and new LAMA use was associated with a 1.52 fold (95% CI, 1.28-1.80; P less than .001) increased risk. In patients with prevalent LABA or LAMA use, the risk of CVD was absent or reduced.

Key limitations included the omission of contributors to cardiovascular disease, including smoking status and alcohol consumption, in the final analysis. Also, the contribution of worsening COPD to cardiovascular events was not accounted for.

Bottom line: Initiation of inhaled LABAs or LAMAs in patients with COPD is associated with a 1.5-fold increased risk of cardiovascular disease – including emergency or inpatient care for coronary artery disease, heart failure, ischemic stroke, or arrhythmia – in the first 30 days.

Citation: Wang MT et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease. JAMA Intern Med. 2018; 178(2):229-38.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Long-acting inhaled bronchodilator use (LABA or LAMA) in patients with COPD is the mainstay of treatment. Prior studies have reported a possible interaction between LABA or LAMA use and increased rates of cardiovascular events; however, the results have been variable. The findings have been confounded by incomplete medical records, exclusion of patients with CVD in bronchodilator trials, and high patient drop out rates. This study aims to assess the association between LABA or LAMA use in patients with COPD and the risk of CVD.

Study design: Nested case control study.

Setting: Taiwanese national database.

Synopsis: This study included 284,200 LABA and LAMA naive patients who were aged 40 years or older and had COPD (mean age, 71.4 years); it retrieved health care claims data from 2007 through 2011 for these patients from the Taiwan National Health Insurance Research Database. During a mean follow-up of 2.0 years, 37,719 patients experienced a cardiovascular event, and 146,139 matched controls were identified. LABA or LAMA use was measured in the year preceding the cardiovascular event and stratified by duration since initiation of LABA or LAMA treatment. Logistical regression was performed to estimate the odds ratios of CVD from LABA and LAMA treatment. New LABA use was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) increased cardiovascular risk within 30 days of initiation, and new LAMA use was associated with a 1.52 fold (95% CI, 1.28-1.80; P less than .001) increased risk. In patients with prevalent LABA or LAMA use, the risk of CVD was absent or reduced.

Key limitations included the omission of contributors to cardiovascular disease, including smoking status and alcohol consumption, in the final analysis. Also, the contribution of worsening COPD to cardiovascular events was not accounted for.

Bottom line: Initiation of inhaled LABAs or LAMAs in patients with COPD is associated with a 1.5-fold increased risk of cardiovascular disease – including emergency or inpatient care for coronary artery disease, heart failure, ischemic stroke, or arrhythmia – in the first 30 days.

Citation: Wang MT et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease. JAMA Intern Med. 2018; 178(2):229-38.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Long-acting inhaled bronchodilator use (LABA or LAMA) in patients with COPD is the mainstay of treatment. Prior studies have reported a possible interaction between LABA or LAMA use and increased rates of cardiovascular events; however, the results have been variable. The findings have been confounded by incomplete medical records, exclusion of patients with CVD in bronchodilator trials, and high patient drop out rates. This study aims to assess the association between LABA or LAMA use in patients with COPD and the risk of CVD.

Study design: Nested case control study.

Setting: Taiwanese national database.

Synopsis: This study included 284,200 LABA and LAMA naive patients who were aged 40 years or older and had COPD (mean age, 71.4 years); it retrieved health care claims data from 2007 through 2011 for these patients from the Taiwan National Health Insurance Research Database. During a mean follow-up of 2.0 years, 37,719 patients experienced a cardiovascular event, and 146,139 matched controls were identified. LABA or LAMA use was measured in the year preceding the cardiovascular event and stratified by duration since initiation of LABA or LAMA treatment. Logistical regression was performed to estimate the odds ratios of CVD from LABA and LAMA treatment. New LABA use was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) increased cardiovascular risk within 30 days of initiation, and new LAMA use was associated with a 1.52 fold (95% CI, 1.28-1.80; P less than .001) increased risk. In patients with prevalent LABA or LAMA use, the risk of CVD was absent or reduced.

Key limitations included the omission of contributors to cardiovascular disease, including smoking status and alcohol consumption, in the final analysis. Also, the contribution of worsening COPD to cardiovascular events was not accounted for.

Bottom line: Initiation of inhaled LABAs or LAMAs in patients with COPD is associated with a 1.5-fold increased risk of cardiovascular disease – including emergency or inpatient care for coronary artery disease, heart failure, ischemic stroke, or arrhythmia – in the first 30 days.

Citation: Wang MT et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease. JAMA Intern Med. 2018; 178(2):229-38.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Antibiotic use is associated with an increased risk of C. difficile infection. Multiple studies have investigated the effects of probiotics in reducing the risk of C. difficile infection with varied results. This meta-analysis aims to assess the efficacy and safety of probiotics in reducing the risk of CDAD in patients taking antibiotics.

Study design: Meta-analysis.

Setting: A comprehensive electronic search for randomized, controlled trials investigating probiotics for prevention of CDAD or C. difficile infection were considered for inclusion. There were no language, publication status, or date limits applied.

Synopsis: This meta-analysis included 31 trials (8,672 participants) evaluating the relationship between probiotics and CDAD. The outcomes were pooled using a random effects model to calculate risk ratios and 95% confidence intervals. A complete case analysis suggested that probiotics reduce the risk of CDAD by 60% (1.5% vs. 4.0%; relative risk, 0.40; 95% confidence interval, 0.3-0.52), although a post-hoc subgroup analysis showed a statistically significant benefit only among patients with a high CDAD baseline risk (greater than 5%). Adverse events were assessed in 32 trials (8,305 participants), and the pooled analysis indicated that probiotic use reduced the risk of adverse events by 17% (RR, 0.83; 95% CI, 0.71-0.97).

Limitations to this meta-analysis include missing data from patients lost to follow-up and lack of success in testing all fecal samples. Lastly, that the strongest data for the beneficial effects of probiotics were demonstrated in patients with a high baseline risk of developing CDAD limits the study’s applicability to the general population.

Bottom line: Probiotic use in immunocompetent patients undergoing treatment with antibiotics decreases the incidence of CDAD without an increase in adverse events.

Citation: Goldenberg JZ et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017. doi: 10.1002/14651858.CD006095.pub4.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Antibiotic use is associated with an increased risk of C. difficile infection. Multiple studies have investigated the effects of probiotics in reducing the risk of C. difficile infection with varied results. This meta-analysis aims to assess the efficacy and safety of probiotics in reducing the risk of CDAD in patients taking antibiotics.

Study design: Meta-analysis.

Setting: A comprehensive electronic search for randomized, controlled trials investigating probiotics for prevention of CDAD or C. difficile infection were considered for inclusion. There were no language, publication status, or date limits applied.

Synopsis: This meta-analysis included 31 trials (8,672 participants) evaluating the relationship between probiotics and CDAD. The outcomes were pooled using a random effects model to calculate risk ratios and 95% confidence intervals. A complete case analysis suggested that probiotics reduce the risk of CDAD by 60% (1.5% vs. 4.0%; relative risk, 0.40; 95% confidence interval, 0.3-0.52), although a post-hoc subgroup analysis showed a statistically significant benefit only among patients with a high CDAD baseline risk (greater than 5%). Adverse events were assessed in 32 trials (8,305 participants), and the pooled analysis indicated that probiotic use reduced the risk of adverse events by 17% (RR, 0.83; 95% CI, 0.71-0.97).

Limitations to this meta-analysis include missing data from patients lost to follow-up and lack of success in testing all fecal samples. Lastly, that the strongest data for the beneficial effects of probiotics were demonstrated in patients with a high baseline risk of developing CDAD limits the study’s applicability to the general population.

Bottom line: Probiotic use in immunocompetent patients undergoing treatment with antibiotics decreases the incidence of CDAD without an increase in adverse events.

Citation: Goldenberg JZ et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017. doi: 10.1002/14651858.CD006095.pub4.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Background: Antibiotic use is associated with an increased risk of C. difficile infection. Multiple studies have investigated the effects of probiotics in reducing the risk of C. difficile infection with varied results. This meta-analysis aims to assess the efficacy and safety of probiotics in reducing the risk of CDAD in patients taking antibiotics.

Study design: Meta-analysis.

Setting: A comprehensive electronic search for randomized, controlled trials investigating probiotics for prevention of CDAD or C. difficile infection were considered for inclusion. There were no language, publication status, or date limits applied.

Synopsis: This meta-analysis included 31 trials (8,672 participants) evaluating the relationship between probiotics and CDAD. The outcomes were pooled using a random effects model to calculate risk ratios and 95% confidence intervals. A complete case analysis suggested that probiotics reduce the risk of CDAD by 60% (1.5% vs. 4.0%; relative risk, 0.40; 95% confidence interval, 0.3-0.52), although a post-hoc subgroup analysis showed a statistically significant benefit only among patients with a high CDAD baseline risk (greater than 5%). Adverse events were assessed in 32 trials (8,305 participants), and the pooled analysis indicated that probiotic use reduced the risk of adverse events by 17% (RR, 0.83; 95% CI, 0.71-0.97).

Limitations to this meta-analysis include missing data from patients lost to follow-up and lack of success in testing all fecal samples. Lastly, that the strongest data for the beneficial effects of probiotics were demonstrated in patients with a high baseline risk of developing CDAD limits the study’s applicability to the general population.

Bottom line: Probiotic use in immunocompetent patients undergoing treatment with antibiotics decreases the incidence of CDAD without an increase in adverse events.

Citation: Goldenberg JZ et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017. doi: 10.1002/14651858.CD006095.pub4.

Dr. Skinner is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.