tiotropium-bromide and Myocardial-Infarction

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

Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients.. Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI.. Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2) = 0%; p = 0.8090).. An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium's cardiovascular risk.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Cholinergic Antagonists; Epidemiologic Methods; Humans; Muscarinic Antagonists; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Risk Factors; Scopolamine Derivatives; Tiotropium Bromide

There are safety concerns regarding the use of anticholinergics in the COPD patient population. The purpose of this review was to evaluate the cardiovascular risk of regular use of inhaled tiotropium bromide in patients with COPD of any severity.. Systematic searches were conducted in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, manufactures' trial register, and FDA databases, without language restriction. Primary outcomes were a composite of major adverse cardiovascular events, cardiovascular mortality, and nonfatal myocardial infarction (MI) or stroke during the treatment period. Relative risks (RR) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I2 statistic.. Nineteen randomized controlled trials (18,111 participants) were selected. There was no difference in the incidence of adverse cardiovascular events (RR=0.96; 95% CI, 0.82-1.12, I2=6%). Among individual components of the composite outcome, tiotropium did not significantly increase the risk of cardiovascular death (RR=0.93; 95% CI, 0.73-1.20, I2=1%), nonfatal MI (RR=0.84; 95% CI, 0.64-1.09, I2=0%), and nonfatal stroke (RR=1.04; 95% CI, 0.78-1.39, I2=0%). A smoking history of > or = 55 pack-years presented a trend to a higher rate of cardiovascular adverse events in patients receiving tiotropium.. Compared with control (placebo or salmeterol), tiotropium did not significantly increase the risk of adverse major cardiovascular events among COPD patients. Subgroup analysis suggested that smoking history can modify the risk of cardiovascular adverse events.

Topics: Administration, Inhalation; Bronchodilator Agents; Humans; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Assessment; Scopolamine Derivatives; Stroke; Tiotropium Bromide

Inhaled anticholinergics (ipratropium bromide or tiotropium bromide) are widely used in patients with chronic obstructive pulmonary disease (COPD) but their effect on the risk of cardiovascular outcomes is unknown.. To ascertain the cardiovascular risks of inhaled anticholinergics, including cardiovascular death, myocardial infarction (MI), and stroke.. Systematic searches were conducted on March 19, 2008, of relevant articles in MEDLINE, the Cochrane Database of systematic reviews, regulatory authority Web sites in the United States and the United Kingdom, and manufacturers' trial registries with no date restrictions.. Randomized controlled trials of any inhaled anticholinergic for treatment of COPD that had at least 30 days of treatment and reported on cardiovascular events.. The primary outcome was a composite of cardiovascular death, MI, or stroke. The secondary outcome was all-cause mortality. Relative risks (RRs) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I(2) statistic.. After a detailed screening of 103 articles, 17 trials enrolling 13,645 [corrected] patients were analyzed. Follow-up duration ranged from 6 weeks to 5 years. Cardiovascular death, MI, or stroke occurred in 134 of 6984 [corrected] patients (1.9%) [corrected] receiving inhaled anticholinergics and 83 of 6661 [corrected] patients (1.2%) receiving control therapy (RR, 1.60 [corrected] [95% confidence interval {CI}, 1.22-2.10]; [corrected] P < .001, I(2) = 0%). Among individual components of the primary end point, inhaled anticholinergics significantly increased the risk of MI (RR, 1.52 [95% CI 1.04-2.22]; [corrected] P = .03, I(2) = 0%) and cardiovascular death (RR, 1.92 [95% CI, 1.23-3.00]; P = .004, [corrected] I(2) = 0%) without a statistically significant increase in the risk of stroke (RR, 1.46 [95% CI, 0.81-2.62]; P = .20, I(2) = 0%). All-cause mortality was reported in 146 [corrected] of the patients treated with inhaled anticholinergics (2.1%) and 108 [corrected] of the control patients (1.6%) (RR, 1.29 [95% CI, 1.00-1.65]; P = .05, I(2) = 0%) [corrected] A sensitivity analysis restricted to 6 [corrected] long-term trials (>6 months) confirmed the significantly increased risk of cardiovascular death, MI, or stroke (2.9% of patients treated with anticholinergics vs 1.8% of the control patients; RR, 1.73 [95% CI, 1.27-2.35]; [corrected] P < .001, I(2) = 0%).. Inhaled anticholinergics are associated with a significantly increased risk of cardiovascular death, MI, or stroke among patients with COPD.

Topics: Administration, Inhalation; Cardiovascular Diseases; Cholinergic Antagonists; Humans; Ipratropium; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk; Scopolamine Derivatives; Stroke; Tiotropium Bromide

The long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safety study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists.. To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, long-acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA.. This population-based cohort study included patients with COPD aged ≥40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Aurum database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables.. The study included 11,121 new users of aclidinium, 4804 of aclidinium/formoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/formoterol) to 12.4 (LAMA/LABA), for stroke ranged from 4.8 (aclidinium/formoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/formoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/formoterol, 0.95 [0.60-1.52], and highest for LAMA/LABA, 1.23 [0.91-1.67]), stroke (lowest for aclidinium/formoterol, 0.64 [0.39-1.06], and highest for tiotropium, 1.02 [0.81-1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75-1.16], and highest for LAMA/LABA, 1.24 [0.97-1.59]).. Risks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/formoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Bronchodilator Agents; Cohort Studies; Drug Therapy, Combination; Formoterol Fumarate; Humans; Muscarinic Antagonists; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Stroke; Tiotropium Bromide

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

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; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Ipratropium; Male; Myocardial Infarction; Myocardial Ischemia; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Assessment; Scopolamine Derivatives; Stroke; Tiotropium Bromide

Topics: Administration, Inhalation; Bronchodilator Agents; Cause of Death; Evidence-Based Medicine; Female; Humans; Male; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk Assessment; Scopolamine Derivatives; Stroke; Survival Analysis; Tiotropium Bromide; United States; United States Food and Drug Administration

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: Administration, Inhalation; Albuterol; Bronchodilator Agents; Drug Therapy, Combination; Humans; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide