Resting heart rate is a risk factor for mortality in chronic obstructive pulmonary disease, but not for exacerbations or pneumonia.

BACKGROUND: Although it is known that patients with chronic obstructive pulmonary disease (COPD) generally do have an increased heart rate, the effects on both mortality and non-fatal pulmonary complications are unclear. We assessed whether heart rate is associated with all-cause mortality, and non-fatal pulmonary endpoints. METHODS: A prospective cohort study of 405 elderly patients with COPD was performed. All patients underwent extensive investigations, including electrocardiography. Follow-up data on mortality were obtained by linking the cohort to the Dutch National Cause of Death Register and information on complications (exacerbation of COPD or pneumonia) by scrutinizing patient files of general practitioners. Multivariable cox regression analysis was performed. RESULTS: During the follow-up 132 (33%) patients died. The overall mortality rate was 50/1000 py (42-59). The major causes of death were cardiovascular and respiratory. The relative risk of all-cause mortality increased with 21% for every 10 beats/minute increase in heart rate (adjusted HR: 1.21 [1.07-1.36], p = 0.002). The incidence of major non-fatal pulmonary events was 145/1000 py (120-168). The risk of a non-fatal pulmonary complication increased non-significantly with 7% for every 10 beats/minute increase in resting heart rate (adjusted HR: 1.07 [0.96-1.18], p = 0.208). CONCLUSIONS: Increased resting heart rate is a strong and independent risk factor for all-cause mortality in elderly patients with COPD. An increased resting heart rate did not result in an increased risk of exacerbations or pneumonia. This may indicate that the increased mortality risk of COPD is related to non-pulmonary causes. Future randomized controlled trials are needed to investigate whether heart-rate lowering agents are worthwhile for COPD patients.

Safety information on QT-interval prolongation: comparison of European Union and United States drug labeling.

Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approved (1st January 2006 to 1st June 2012) in the European Union (EU) and the United States (US), of which 66 mentioned the term 'QT' (two EU only, 28 US only, 36 both). The agreement between authorities about the message on QT prolongation (does not prolong, unclear, possibly prolongs, prolongs) was moderate (kappa 0.434). However, the agreement in expected clinical decisions based on the product labels was much higher (kappa 0.673). The US drug label tends to be more explicit, especially when it considers absence of QT effects.

Quality of drug label information on QT interval prolongation.

BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product characteristics (SPC) of recently approved medicinal products. METHODS: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT-prolongation': 100%). CONCLUSIONS: The extent and content of information on QT-prolongation varies considerably between SPCs, and in almost half of the drugs a clear message on QT-prolongation was lacking in the SPC.

QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population: a cross-sectional study.

OBJECTIVE: To investigate the association between the use of a selective serotonin reuptake inhibitor (SSRI) and the occurrence of QT interval prolongation in an elderly surgical population. METHOD: A cross-sectional study was conducted among patients (> 60 years) scheduled for outpatient preanesthesia evaluation in the period 2007 until 2012. The index group included elderly users of an SSRI. The reference group of nonusers of antidepressants was matched to the index group on sex and year of scheduled surgery (ratio, 1:1). The primary outcome was the occurrence of QT interval prolongation shown on electrocardiogram. The QT interval was corrected for heart rate (QTc interval). The secondary outcome was the duration of the QTc interval. The outcomes were adjusted for confounding by using regression techniques. RESULTS: The index and reference groups included 397 users of an SSRI and 397 nonusers, respectively. QTc interval prolongation occurred in 25 (6%) and 19 (5%) index and reference patients, respectively. After adjustment for confounding, users of an SSRI did not have a higher risk for QTc interval prolongation compared to nonusers: OR = 1.1 (95% CI, 0.5 to 2.0). The adjusted mean QTc interval length in users of an SSRI and nonusers was comparable (difference of 1.5 milliseconds [95% CI, -1.8 to 4.8]). Use of the most frequently used SSRIs citalopram and paroxetine was not associated with a higher risk of QTc interval prolongation nor with lengthening of the QTc interval duration. CONCLUSIONS: The use of an SSRI by elderly surgical patients was not associated with the occurrence of QT interval prolongation.

Electrocardiographic characteristics of patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease. Electrocardiography (ECG) carries information about cardiac disease and prognosis, but studies comparing ECG characteristics between patients with and without COPD are lacking. We related ECG characteristics of patients with COPD, to ECG characteristics of patients without COPD, and determined whether ECG abnormalities are related to COPD severity. A cross-sectional study was conducted within a cohort of 243 COPD patients, aged 65 years or older. All patients underwent extensive examinations, including resting 12-lead ECG and pulmonary function tests. The reference group (n = 293) was a sample from the general population, also aged 65 or older, without COPD. Abnormal ECGs were more prevalent in COPD patients (50%) than in patients without COPD (36%, p = 0.054). Conduction abnormalities were the most common ECG abnormality in COPD patients (28%) being significantly more prevalent than in patients without COPD (11%, p < 0.001). The mean heart rate was higher in COPD patients (72 bpm (SD 14)) compared to controls (65 bpm (SD 13), p < 0.001), and QTc prolongation was less frequent in COPD patients (9% versus 14%, p = 0.01). The prevalence of ECG abnormalities increased with severity of pulmonary obstruction. ECG abnormalities, especially conduction abnormalities are common in COPD patients, and the prevalence of ECG abnormalities increases with severity of COPD. This underlines the importance of an integrated-care approach for COPD patients, paying attention to early detection of unrecognized coexisting cardiac disorders.

Smoking cessation strategies in patients with COPD.

Smoking cessation is the cornerstone of treatment of chronic obstructive pulmonary disease (COPD) patients. This systematic review evaluates the effectiveness of behavioural and pharmacological smoking cessation strategies in COPD patients. MEDLINE was searched from January 2002 to October 2011. Randomised controlled trials evaluating the effect of smoking cessation interventions for COPD patients, published in English, were selected. The methodological quality of included trials was assessed using the Delphi list by two reviewers independently. The relative risks of smoking cessation due to the intervention, compared with controls, were calculated. Eight studies met the inclusion criteria. Heterogeneity was observed for study population, the intervention strategy, the follow-up period and the outcome. According to the Delphi list methodological quality scores, five studies were considered to be of acceptable quality. Pharmacological therapy combined with behavioural counselling was more effective than each strategy separately. In COPD patients, the intensity of counselling did not seem to influence the results, nor did the choice of drug therapy make a difference. This systematic review makes clear that in COPD patients, pharmacological therapy combined with behavioural counselling is more effective than each strategy separately. Neither the intensity of counselling nor the type of anti-smoking drug made a difference.

Cardiac arrhythmias in adult patients with asthma.

OBJECTIVE: The pathogenesis of cardiac arrhythmias in asthma patients has not been fully elucidated. Adverse drug effects, particularly those of ß2-mimetics, may play a role. The aim of this study was to determine whether asthma is associated with the risk of cardiac arrhythmias and electrocardiographic characteristics of arrhythmogenicity (ECG) and to explore the role of ß2-mimetics. METHODS: A cross-sectional study was conducted among 158 adult patients with a diagnosis of asthma and 6303 participants without asthma from the cohort of the Utrecht Health Project-an ongoing, longitudinal, primary care-based study. All patients underwent extensive examinations, including resting 12-lead electrocardiogram (ECG) and pulmonary function tests. The primary outcome was "any arrhythmia on the ECG" (including tachycardia, bradycardia, premature ventricular contraction (PVC), and atrial fibrillation or flutter). Secondary outcomes were tachycardia, bradycardia, PVC, atrial fibrillation or flutter, mean heart rate, mean corrected QT (QTc) interval length, and prolonged QTc interval. RESULTS: Tachycardia and PVCs were more prevalent in patients with asthma (3% and 4%, respectively) than those without asthma (0.6%, p < .001; 2%, p = .03, respectively). The prevalence of QTc interval prolongation was similar in participants with (2%) and without asthma (3%, odds ratio [OR]: 0.6 and 95% confidence interval [95% CI]: 0.2-2.0). In 74 asthma patients, who received ß2-mimetics, tachycardia and PVCs were more common (OR: 12.4 [95% CI: 4.7-32.8] and 3.7 [95% CI: 1.3-10.5], respectively). CONCLUSIONS: The adult patients with asthma more commonly show tachycardia and PVCs on the ECG than those without asthma. The patients with asthma received ß2-mimetics; the risk of tachycardia and PVCs is even more pronounced.