Abstract
BackgroundTiotropium is an anticholinergic bronchodilator for symptom relief and reducing exacerbations with an established safety profile in patients with chronic obstructive pulmonary disease (COPD). Using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study, we re-evaluated the safety of tiotropium HandiHaler® in patients who experienced recent myocardial infarction (MI), heart failure or unstable rhythm disorder during the study.MethodsA post-hoc analysis of all-cause mortality and serious cardiac adverse events (cardiac SAEs), including cardiac deaths and death unknown, was conducted in patients who had experienced cardiac arrhythmia, MI or cardiac failure during UPLIFT® and who completed the study. Descriptive analyses were performed.ResultsMost patients experiencing cardiac events, for which they would have been excluded at baseline, remained in the trial. Kaplan-Meier analyses revealed a trend to later occurrence of cardiac SAEs with tiotropium HandiHaler® versus placebo. Patients who experienced a cardiac event and continued in UPLIFT® were not found to be at subsequently increased risk of all-cause mortality or cardiac SAEs with tiotropium treatment. Evaluation of deaths by major adverse cardiac events composite endpoints also showed that patients treated with tiotropium were not at increased risk of mortality or cardiac SAEs compared with placebo.ConclusionsRisk of cardiac events, mortality or SAEs was not increased by tiotropium in patients experiencing cardiac events for which they would have been excluded at study baseline. The findings support the cardiac safety of tiotropium HandiHaler® in patients with COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0216-4) contains supplementary material, which is available to authorized users.
Highlights
Tiotropium is a once-daily maintenance anticholinergic bronchodilator for the relief of symptoms and reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD) [1,2,3]
Kaplan-Meier analysis revealed a trend to later onset of the initial cardiac arrhythmia event in the tiotropium group (Figure 1A)
Mean treatment duration after the first cardiac arrhythmia event was 576.0 days for placebo and 518.8 days (SD: 438.0) for tiotropium patients. Among those patients who were administered placebo and who experienced a cardiac arrhythmia during the study, 60.2% (109/181) subsequently experienced an Serious adverse event (SAE) and 20.4% (37/181) experienced a cardiac SAE
Summary
Full details of the UPLIFT® methodology, including patient eligibility criteria, have been published previously [9]. Analysis of outcomes in patients experiencing a cardiac event during the study Patients who were selected for the post-hoc analyses had to have experienced a cardiac event with onset during treatment, but following the first occurrence of the cardiac event, they did not withdraw from UPLIFT® (either due to the event or for another reason). For the vital status analysis, FAEs were counted if the death occurred ≥1 day following the first cardiac event of interest (arrhythmia, MI or cardiac failure) and within 1440 days of drug start. A composite endpoint of MACE was included in the analyses This endpoint represents fatal events in the system organ class (SOC) cardiac disorders and SOC vascular disorders combined with MI (fatal and nonfatal), stroke (fatal and non-fatal) and the following preferred terms: sudden death, sudden cardiac death and cardiac death.
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