ticagrelor and Pulmonary-Disease--Chronic-Obstructive

To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence.. This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21-3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58-1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm.. In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected.. NCT01813435.

Topics: Aged; Coronary Artery Disease; Drug Administration Schedule; Dual Anti-Platelet Therapy; Dyspnea; Female; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Adenosine; Aged; Anticoagulants; Apoptosis; Blood Platelets; Clopidogrel; Coronary Artery Disease; Cytokines; Endothelium, Vascular; Female; Human Umbilical Vein Endothelial Cells; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Nitric Oxide; Percutaneous Coronary Intervention; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Ticagrelor; Ticlopidine

Topics: Coronary Artery Disease; Diagnostic Errors; Endothelium, Vascular; Female; Humans; Long Term Adverse Effects; Male; Mass Screening; Middle Aged; Outcome Assessment, Health Care; Peak Expiratory Flow Rate; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Surveys and Questionnaires; Ticagrelor

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients.. In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results.. In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Dyspnea; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Ticagrelor is a direct-acting, reversibly binding, oral P2Y12 platelet inhibitor that reduces thrombotic cardiovascular events in patients with acute coronary syndrome. Dyspnea is one of the most commonly reported adverse events associated with ticagrelor.. To determine the effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease (COPD) patients.. Two randomized, double-blind, placebo-controlled, two-way crossover, single-center studies were conducted: 1) healthy elderly volunteers (55-75 years; n = 12); 2) patients with mild asthma (n = 11) or mild-to-moderate COPD (n = 7). Subjects were randomized to receive ticagrelor (a single 450 mg dose, 180 mg 12 hours later, twice daily for 2 days, and once on day 4) or placebo, with a 7 day washout. Pulmonary function at rest and during exercise was monitored using similar schedules and assessments across the two studies.. Resting pulmonary function parameters, including respiratory rate, minute ventilation, or tidal volume, were similar between ticagrelor and placebo in any cohort. Furthermore, bronchospasm (as determined by spirometry and pulse oximetry), was not observed with either ticagrelor or placebo in any cohort. Perception of breathing was generally similar following ticagrelor or placebo. Exercise performance was not affected, and no clinically relevant differences were seen in pulmonary parameters during exercise for ticagrelor or placebo. There was no apparent relationship between plasma concentrations of ticagrelor and its main metabolite and pulmonary function. Ticagrelor was well tolerated in all cohorts. Study limitations include the use of relatively few subjects without documented coronary artery disease.. Short-term administration of high doses of ticagrelor did not appear to alter pulmonary function at rest and during exercise in subjects at risk of (healthy elderly) or with respiratory impairment (mild asthma or mild-to-moderate COPD).

Topics: Adenosine; Aged; Asthma; Double-Blind Method; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Purinergic P2Y Receptor Antagonists; Respiratory Rate; Respiratory Transport; Ticagrelor

Ticagrelor is a reversible inhibitor of platelet-aggregation, and is used instead of clopidogrel in the treatment of acute coronary syndrome (ACS). Ticagrelor has documented better outcomes as shown in the PLATO-study, when compared to clopidogrel. However, more major non-CABG bleedings are observed with ticagrelor. Treatment of ACS with platelet-inhibitors is the standard, but there is no antidote for ticagrelor or clopidogrel, making haemostasis problematic in the case of a major bleeding. The following case describes a 76-year-old woman, who after admission for chronic obstructive pulmonary disease and ACS, was treated with ticagrelor and developed a major gastrointestinal bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Artery Bypass; Female; Gastrointestinal Hemorrhage; Humans; Pulmonary Disease, Chronic Obstructive; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome