Breathing patterns and ventilator efficiency in patients with acute coronary syndrome receiving ticagrelor - an analysis of the Bern Rehab Registry

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Abstract Background Ticagrelor has been documented to cause dyspnea, though without inducing significant hyperventilation or metabolic alterations at rest. We analysed cardiopulmonary exercise test (CPET) data of patients with acute coronary syndrome (ACS) under different dual antiplatelet therapies (DAPT) at beginning and end of a 12-week ambulatory cardiac rehabilitation (CR) programme. Purpose To describe breathing patterns and ventilatory efficiency of ticagrelor during exercise compared to other DAPTs used in ACS. Methods Data from the Bern Rehab Registry of patients completing CR after ACS between 1.1.2021 and 31.5.2024 were included in the analysis. All patients performed a CPET on a stationary bicycle. Ventilation (VE), end-tidal partial pressure of carbon dioxide (PetCO2) were determined during the last minute of a 3-min resting period in sitting position on the ergometer and at peak exercise. Peak power output and peak oxygen uptake (VO2) per kg of body weight were determined. The VE/VCO2 slope was determined between the start of the ramp to the second vntilatory threshold. Mixed linear models were performed for CPET parameters with fixed effects type of DAPT and time (including interaction effect) and patients as random intercepts, adjusted for age, sex, and heart failure (HF) group (no HF, HF with preserved ejection fraction (EF), HF with mildly reduced EF, and HF with reduced EF). Results 392 patients completed the entry examination of whom 329 (83.9%) also completed the conclusion examination. 198 (50.5%), 120 (30.6%), 74 (18.9%) patients were on ticagrelor, prasugrel, or clopidogrel, respectively. Seven patients (3.2%) discontinued ticagrelor (3.2%) because of dyspnea. Patients on prasugrel were significantly fitter with higher peak power output and VO2 than patients on ticagrelor and patients on clopidrogrel, while the latter two groups were comparable with regard to fitness (Figure 1). At CR entry, patients on ticagrelor had significantly lower PetCO2 at rest (p=0.002) and peak exercise (p=0.003) and higher VE/VCO2 slope (p=0.023) compared to patients on clopidogrel. Patients who discontinued ticagrelor during CR before the conclusion visit increased their PetCO2 significantly more at rest and peak exercise (p=0.005 and p=0.001, respectively, for group x time interaction) and decreased their VE/VCO2 slope significantly more than all other patients (p=0.046 for group x time interaction). VE, breathing frequency and tidal volume at rest were not different between DAPT groups. Conclusion Patients on ticagrelor and clopidogrel were comparable for fitness, but those on ticagrelor had lower PetCO2 at rest and peak exercise in the absence of marked hyperventilation, suggesting mild respiratory alkalosis. Abnormally low PetCO2 resolved upon discontinuation with signs of overcompensation. Our results are in line with previously documented increased chemosensitivity in patients on ticagrelor compared to clopidogrel.1Figure 1

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