Cardiac safety of tiotropium in patients with cardiac events: a retrospective analysis of the UPLIFT® trial

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.

Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care

“…Similarly, the cardiac safety of inhaled antimuscarinic agents has been debated for more than a decade (17,100). Short-acting bronchodilators, such as ipratropium, may slightly increase the risk of HF (101), whereas there seems to be no additional risk of incident HF due to tiotropium use (102,103) or with newer long-acting antimuscarinic antagonists (LAMAs) (i.e., glycopyrronium [104], aclidinium [105], and umeclidinium [106]) or even with the LABA/LAMA combination indacaterol/glycopyrronium (107).…”

An update on LAMA/LABA combinations for COPD

“…Increased mortality was noted with inhaled tiotropium via the Respimat device,34 although a study in 17,135 people with a mean follow-up of 2.3 years found tiotropium delivered by Respimat to be non-inferior to tiotropium delivered by Handihaler with respect to the risk of death 35. Post-hoc analysis of data from the 4-year UPLIFT study reported no excess of deaths or serious cardiac events in people receiving tiotropium via the Handihaler compared with placebo 36. Patients treated with tiotropium were not found to be at increased risk of cardiac events compared with placebo.…”

Receptores muscarínicos na doença pulmonar obstrutiva crônica: o que é importante saber da Biologia à prática clínica?

“…A prevenção das exacerbações com tiotrópio em pacientes com DPOC apresentou um excesso de eventos isquêmicos coronários graves com o tiotrópio em comparação com o salmeterol. Os autores recomendam cautela na prescrição de anticolinérgicos inalados para pacientes com arritmias pré-existentes ou doenças cardíacas [16][17][18] . Concluímos que a prescrição de medicamentos como os antimuscarínicos é um item importante para a reabilitação pulmonar em pacientes com DPOC porque melhoram os sintomas, particularmente a dispneia e a capacidade de fazer as atividades diárias.…”