Effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease patients

Abstract

Background:

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.

Objective:

To determine the effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease (COPD) patients.

Methods:

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.

Results:

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.

Conclusions:

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).

Keywords::

• Asthma
• Chronic obstructive pulmonary disease
• Dyspnea
• Exercise test
• Respiratory function tests
• Ticagrelor

Transparency

Declaration of funding

This study was funded by AstraZeneca.

Declaration of financial/other relationships

K.B., J.M., and R.T. have disclosed that they are employees of AstraZeneca.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Dr. E. Bernton (Principal Investigator, healthy elderly study) and his team at the Clinical Pharmacology Research Unit (Harbor Hospital Center, Baltimore, MD, USA) and Dr. J Herron (Principal Investigator, asthma/COPD study) and his team at Arkansas Research Medical Testing LLC (Little Rock, AR, USA). H Sillén (Bioanalyses Responsible Scientist; AstraZeneca R&D, Mölndal, Sweden), staff at York Bioanalytical Solutions, York, UK, and Quality Data Services, King of Prussia, PA, USA are acknowledged for their contribution to the pharmacokinetic sample analyses and data management. Editorial support in the preparation of this manuscript was provided by Jackie Phillipson (Medical Writer, Gardiner–Caldwell Communications); this support was funded by AstraZeneca.