Republished: Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications.
ABSTRACT The majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associated with a statistically significant increased risk of mortality (RR 1.52; 95% CI 1.06 to 2.16) and cardiovascular death (RR 2.05; 95% CI 1.06 to 3.99) compared with placebo in a meta-analysis of clinical trials. In the largest study, the subgroup of patients with COPD in the Respimat group with known rhythm and cardiac disorders at baseline had an especially high risk for cardiac death (RR 8.6; 95% CI 1.1 to 67.2). Although there was no significantly increased risk of mortality (HR 0.89; 95% CI 0.79 to 1.02) or myocardial infarction (MI) (RR 0.73; 95% CI 0.53 to 1.00) with tiotropium handihaler in the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, the reported excess of angina (RR 1.44; 95% CI 0.91 to 2.26), imbalance in strokes related to ischaemia and rates of supraventricular tachyarrhythmias are consistent with the pro-ischemic and pro-arrhythmic effects. The subjects at greatest risk of cardiovascular death, such as those with a recent history of MI, unstable or life-threatening cardiac arrhythmias or hospitalisation with heart failure, were excluded from the UPLIFT trial. The Prevention of Exacerbations with Tiotropium in COPD trial showed an excess of serious coronary ischaemic events of angina, myocardial ischaemia and MI with the tiotropium Handihaler compared with salmeterol. The authors urge caution in prescribing inhaled anticholinergics for patients with pre-existing arrhythmias or cardiac disorders.
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ABSTRACT: The treatment of older and oldest old patients with COPD poses several problems and should be tailored to specific outcomes, such as physical functioning. Indeed, impaired homeostatic mechanisms, deteriorated physiological systems, and limited functional reserve mainly contribute to this complex scenario. Therefore, we reviewed the main difficulties in managing therapy for these patients and possible remedies. Inhaled long acting beta-agonists (LABA) and anticholinergics (LAMA) are the mainstay of therapy in stable COPD, but it should be considered that pharmacological response and safety profile may vary significantly in older patients with multimorbidity. Their association with inhaled corticosteroids is recommended only for patients with severe or very severe airflow limitation or with frequent exacerbations despite bronchodilator treatment. In hypoxemic patients, long-term oxygen therapy (LTOT) may improve not only general comfort and exercise tolerance, but also cognitive functions and sleep. Non-pharmacological interventions, including education, physical exercise, nutritional support, pulmonary rehabilitation and telemonitoring can importantly contribute to improve outcomes. Older patients with COPD should be systematically evaluated for the presence of risk factors for non-adherence, and the inhaler device should be chosen very carefully. Comorbidities, such as cardiovascular diseases, chronic kidney disease, osteoporosis, obesity, cognitive, visual and auditory impairment, may significantly affect treatment choices and should be scrutinized. Palliative care is of paramount importance in end-stage COPD. Finally, treatment of COPD exacerbations has been also reviewed. Therapeutic decisions should be founded on a careful assessment of cognitive and functional status, comorbidity, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics in order to minimize adverse drug events, drug-drug or drug-disease interactions, and non-adherence to treatment.
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation and punctuated by episodes of acute exacerbation. There is growing recognition that the inflammatory state associated with COPD is not confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs. Epidemiologic and mechanistic studies indicate that COPD is associated with a high frequency of coronary artery disease, congestive heart failure and cardiac arrhythmias, independent of shared risk factors. Possible pathways include complex interrelationships between chronic low-grade systemic inflammation and oxidative stress as well as shared risk factors such as age, cigarette smoking, and environmental pollutants. In this review, we provide an overview of the epidemiologic data linking COPD with cardiovascular disease, comment on the interrelationships among COPD, inflammation, and cardiovascular disease, and highlight diagnostic and therapeutic challenges.Translational Research 10/2013; 162(4):237-251. DOI:10.1016/j.trsl.2013.05.001 · 4.04 Impact Factor
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ABSTRACT: studies have raised concerns that medications with anticholinergic property have potential adverse effects on health outcomes. the objective of this study is to examine the prospective relationships between total anticholinergic burden (ACB) from medications and mortality, and cardiovascular disease (CVD) in a general population. observational study. community cohort. we examined data collected from 21,636 men and women without cancer at the baseline who participated in a baseline survey 1993-97 in the European Prospective Investigation into Cancer (EPIC)-Norfolk. They were followed until 2009/11. we performed Cox-proportional hazards models to determine the associations between total ACB and the subsequent risk of all-cause mortality and incident CVD during the follow-up. there were a total of 4,342 people died and 7,328 had an incident CVD during the study follow-up (total person years = 322,321 years for mortality and 244,119 years for CVD event). Compared with people with no anticholinergic burden (ACB = 0), people with total ACB ≥3 from medications had hazards ratios of 1.83 (1.53, 2.20) and 2.17 (1.87, 2.52) for mortality and CVD incidence outcomes, respectively, after adjusting for potential confounders. Repeating the analyses after excluding people with prevalent illnesses, and events occurring within the first 2 years of follow-up, only slightly attenuated the results. there appear to be a class effect as well as dose-response relationship between the ACB and both outcomes. Future research should focus on understanding the relationship between ACB and mortality, and cardiovascular disease and possibly minimising ACB load where feasible. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: email@example.com.Age and Ageing 11/2014; DOI:10.1093/ageing/afu185 · 3.11 Impact Factor