tiotropium-bromide and Arrhythmias--Cardiac

Topics: Arrhythmias, Cardiac; Benzoxazines; Bronchodilator Agents; Cardiovascular Diseases; Drug Combinations; Heart Failure; Humans; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Tiotropium Bromide

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.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cause of Death; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Ipratropium; Male; Middle Aged; Myocardial Ischemia; Prognosis; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Assessment; Safety Management; Scopolamine Derivatives; Survival Analysis; Tiotropium Bromide; Treatment Outcome

Patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidities may have an increased risk of medication-related cardiac arrhythmias. We therefore performed an analysis of Holter electrocardiogram (ECG) data from two large, long-term, controlled clinical COPD trials to investigate whether tiotropium/olodaterol increased the risk of cardiac arrhythmia and mean heart rate.. After 12 weeks of treatment, there was no difference in the number of patients who had an increase or decrease from baseline in 24-hour supraventricular premature beats or ventricular premature beats between tiotropium/olodaterol 5/5 µg combination therapy and its monocomponents. Compared with baseline, a small but statistically significant increase in adjusted mean heart rate was observed for tiotropium 5 µg (+1.6 beats per minute [bpm]; P=0.0010), but no difference was observed for olodaterol 5 µg (+0.3 bpm; P=0.2778) or tiotropium/olodaterol 5/5 µg (-0.1 bpm; P=0.4607). MACE and fatal MACE were limited to 1 to 3 patients across treatment groups.. Compared with the compounds given as monotherapy, treatment with tiotropium/olodaterol fixed-dose combination therapy is not associated with medically relevant or statistically significant effects on arrhythmia as assessed by Holter ECG. Based on these findings, there is no evidence to assume a clinically relevant impact on cardiac function from dual tiotropium/olodaterol treatment.. TONADO 1 (ClinicalTrials.gov: NCT01431274); TONADO 2 (ClinicalTrials.gov: NCT01431287).

Topics: Administration, Inhalation; Arrhythmias, Cardiac; Benzoxazines; Bronchodilator Agents; Double-Blind Method; Electrocardiography, Ambulatory; Forced Expiratory Volume; Heart Rate; Humans; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Treatment Outcome

The cardiovascular risk of concurrently using long-acting β

Topics: Adrenergic beta-2 Receptor Agonists; Algorithms; Arrhythmias, Cardiac; Bronchodilator Agents; Cardiovascular Diseases; Cholinergic Antagonists; Cohort Studies; Heart Failure; Humans; Muscarinic Antagonists; Myocardial Infarction; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Research Design; Risk Factors; Tiotropium Bromide; Treatment Outcome; United Kingdom

Tiotropium has been associated with an increased risk of mortality and/or cardiovascular events. Recent data from RCTs suggests tiotropium Handihaler to be safe, but its safety has not yet been fully investigated under real-life circumstances.. We conducted 2 nested case-control studies in a COPD cohort from the Dutch IPCI database. In the first case-control study, cases had a cardiovascular or cerebrovascular endpoint (CCVE): stroke and transient ischemic attack (TIA), myocardial infarction, heart failure and/or ventricular arrhythmia. In the second, cases were all patients who died. Cases were matched to controls on age, sex and index date. Conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (CI) for tiotropium vs. long-acting beta-agonists (LABA).. Within a cohort of 6788 COPD patients, 784 CCVE's and 1032 deaths were reported. Compared to current LABA use, use of tiotropium Handihaler was neither associated with an increased risk of a CCVE (OR(adj) 0.89, 95% 0.55-1.44) nor with an increased risk of death (OR(adj) 0.79, 95% CI 0.49-1.28).. In real life, use of tiotropium Handihaler in COPD patients is not associated with an increased risk of a CCVE or mortality compared to LABA.

Topics: Adrenergic beta-Agonists; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Bronchodilator Agents; Cardiovascular Diseases; Case-Control Studies; Cerebrovascular Disorders; Cohort Studies; Confidence Intervals; Databases, Factual; Endpoint Determination; Female; Heart Failure; Humans; Ischemic Attack, Transient; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nebulizers and Vaporizers; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Sex Factors; Stroke; Tiotropium Bromide

Topics: Arrhythmias, Cardiac; Bronchodilator Agents; Dyspnea; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Smoking; Smoking Cessation; Tiotropium Bromide