Ticagrelor is associated with periodic breathing during exercise in coronary patients undergoing cardiac rehabilitation: a retrospective observational study.

PURPOSE: Ticagrelor, a reversible P2Y12 inhibitor widely prescribed after acute coronary syndrome (ACS), induces dyspnoea and central sleep apnoea through effects on respiratory centre activity. During cardiac rehabilitation, we observed apparent ventilatory disturbances in patients receiving ticagrelor during cardiopulmonary exercise tests (CPET). This study aimed to evaluate whether ticagrelor significantly increases the risk of periodic breathing during exercise and whether this impairs functional or metabolic performance.

METHODS

We performed a single-centre retrospective observational study (October 2012-December 2021) including 84 coronary patients (36 ticagrelor, 48 thienopyridines) who underwent cardiac rehabilitation following angioplasty with coronary stenting. The primary endpoint was exercise-induced periodic breathing, defined as ≥ 3 consecutive oscillation cycles of VE, VO2, or VCO2 with amplitude ≥ 30% of mean values. Secondary endpoints were peak VO2, end-tidal CO2 pressure (PETCO2), and ventilatory equivalent for CO2 (EqCO2) at peak VO2. Univariable and multivariable logistic and linear regression analyses were performed (R v4.0.0).

RESULTS

Ticagrelor was independently associated with a > 7-fold increased risk of periodic breathing during exercise in both univariable (OR = 7.82, 95% CI [2.80-24.72], p < 0.001) and multivariable analyses (OR = 7.17, 95% CI [2.31-25.19], p < 0.001), after adjustment for age, BMI, LVEF, smoking, obstructive lung disease, and neurological risk. No significant effect on PETCO2 (p = 0.759) or EqCO2 (p = 0.442) at peak VO2 was observed. In multivariable analysis, patients on ticagrelor had significantly higher peak VO2 than those on thienopyridines (+ 3.17 ml/min/kg, 95% CI [1.34-4.99], p < 0.001).

CONCLUSION

Ticagrelor is significantly associated with periodic breathing during exercise in coronary patients undergoing cardiac rehabilitation. However, this ventilatory disturbance does not impair gas exchange or aerobic capacity. These findings support maintaining ticagrelor therapy in patients presenting with exercise-induced periodic breathing.