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: Chronic obstructive pulmonary disease (COPD) is characterized by a diverse array of pulmonary and nonpulmonary manifestations, but our understanding of COPD pathogenesis and the factors that influence its heterogeneity in disease presentation is poor. Despite this heterogeneity, treatment algorithms are primarily driven by a single measurement, forced expiratory volume in 1 second (FEV1) as a percentage of its predicted value (FEV1%). In 2011, a major shift in Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment recommendations was proposed that stratifies patients with COPD on the basis of symptoms and exacerbation history. This article reviews the work reported in 2013 that enlightens our understanding of COPD with respect to COPD classification systems, phenotype, biomarker, exacerbation, and management for patients with COPD.Tuberculosis and Respiratory Diseases 10/2014; 77(4):155-60.
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ABSTRACT: Small peripheral airways are an important target for the anti-inflammatory treatment of asthma. To make anti-inflammatory drugs (inhaled corticosteroids [ICS]) effectively reach small airways, they should be delivered using inhalation techniques containing high proportions of fine or super-fine particles. Higher proportions of fine particles are associated with higher systemic absorption of ICS leading to an increased risk of endogenous cortisol suppression. Ciclesonide, despite the highest proportion of fine and super-fine particle fractions, is the only ICS not associated with an increased risk of systemic adverse effects, including cortisol suppression. In contrary to ICS, bronchodilators should not be administered to peripheral airways. This does not improve their efficacy and may increase their risk of cardiotoxicity. Thus, from a pharmacological point of view and the theory of aerosols' deposition, fixed combinations of ICS and long-acting beta agonists are always suboptimal. In many cases, the best solution may be to use fine-particle ciclesonide and a non-fine particle beta agonist administered from separate inhalers.Advances in Therapy 08/2014; · 2.44 Impact Factor
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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.Current pharmaceutical design. 01/2015;