tiotropium-bromide and Cerebrovascular-Disorders

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

As COPD patients commonly suffer cardio- and cerebrovascular (CCV) co-morbidities, our purpose was to establish the CCV safety profile of indacaterol, a novel, inhaled, long-acting β(2)-agonist for COPD.. The indacaterol clinical trial database comprised 4635 patients with moderate-to-severe COPD enrolled into studies of ≥6 months' duration treated with indacaterol, placebo or other bronchodilators (formoterol, salmeterol, tiotropium). Adverse events (AEs) were analysed overall and according to Anti-Platelet Trialists' Collaboration (APTC) criteria and baseline cardiovascular risk factors. A subset of patients had Holter monitoring.. Compared with placebo, indacaterol did not increase the risk of CCV AEs; relative risks were not significantly different for indacaterol versus other treatments. In all treatment groups, including placebo, most CCV AEs occurred in patients with pre-existing cardiovascular risk factors. The risk of APTC events (e.g. myocardial infarction, stroke, cardiovascular-related death) was not significantly increased for indacaterol versus placebo. The incidence of notable QTc interval increases >60 ms was low with all active treatments (0-0.5%, versus 0.3% with placebo). Holter monitoring in the subset of patients receiving indacaterol, tiotropium or placebo showed no clinically relevant effect of indacaterol or tiotropium relative to placebo on the development of arrhythmias. The number of deaths adjusted for exposure was lower with all active treatments than with placebo, with a trend to reduced risk with indacaterol (relative risk 0.30, p = 0.054).. The overall CCV safety profile of indacaterol was similar to placebo and comparable with other long-acting bronchodilators, providing reassurance for regular long-term use of indacaterol in COPD. Data for this analysis were pooled from three studies, registered at ClinicalTrials.gov as: NCT00393458, NCT00463567 and NCT00567996.

Topics: Adult; Albuterol; Bronchodilator Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Indans; Male; Middle Aged; Placebos; Pulmonary Disease, Chronic Obstructive; Quinolones; Risk Factors; Salmeterol Xinafoate; Scopolamine Derivatives; Smoking; Tiotropium Bromide

The aim of this study was to examine the risk of cardiovascular diseases among users of both inhaled (ipratropium bromide or tiotropium bromide) and oral (oxybutynin and propantheline, solifenacin, tolterodine) anticholinergics.. A retrospective study was undertaken on data obtained from the Food and Drug Administration (FDA) from subjects who had received either an inhaled or oral form of an anticholinergic drug and experienced some side effect during the period from 1988 to 2009. The recorded data included: patient's age, sex, list of drugs and side effects. Side effect rates for the anticholinergic drugs were compared using univariate (Chi-square) and multivariate (logistic regression) methods.. The files from the FDA held data for 36 491 different subjects, of whom 2610 (7.15%) experienced a cardiovascular or neurovascular side effect. Subjects were classified as taking the oral (45%) or inhaled (55%) class of the drug, with only 109 subjects (0.3%) taking drugs in both forms. Side effect rates differed between anticholinergic drugs. Stroke and hypertension were significantly more common for subjects taking oral anticholinergic drug compared with tiotropium, while other reported vascular side effects (cardiac ischaemia or arrhythmiascardiac failure, cardiac arrest) tended to be more commonly associated with the use of inhaled anticholingerics. These differences persisted after adjustment for age and gender.. This observational study of recorded side effects showed that, except for stroke and hypertension, patients who were treated with an inhaled anticholinergic drug appeared to be at higher risk of developing neurovascular or cardiovascular side effects, than those treated with an oral drug. However, physicians should also be aware that oral anticholinergic drugs may have similar adverse impacts on health. Further studies on the association between anticholinergic drugs and cardiovascular and neurovascular side effects are recommended.

Topics: Administration, Inhalation; Administration, Oral; Aged; Aged, 80 and over; Bronchodilator Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Cholinergic Antagonists; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk; Scopolamine Derivatives; Stroke; Tiotropium Bromide