Rationale and design of PREvalence of DyspneA in patients treated with TicagrelOR (PREDATOR) program

Abstract

Background: Ticagrelor, a reversible P2Y12 inhibitor, is a mainstay of antiplatelet strategy in patients with acute coronary syndrome (ACS). However, a large number of ticagrelor-induced dyspnea decrease patients’ adherence and reduce an overall efficacy of the therapy. Design: The PREDATOR program consists of phase III and IV, multicenter, randomized, double-blind, placebo-controlled clinical trials and preceding pilot studies that assesses the prevalence and treatment of ticagrelor-induced dyspnea in coronary artery disease (CAD) and ACS patients. The PREDATOR LD is designed to evaluate the occurrence of dyspnea after 180 mg ticagrelor loading dose, and relief of dyspnea by theophylline administration in low-to-high risk acute coronary syndromes without ST-segment elevation (NSTE-ACS) and stable CAD designated to undergo invasive treatment. The PREDATOR MD is a cross-over trial in stable CAD patients 1 year after percutaneous coronary intervention for ACS. Enrolled patients will be randomized to one of four antiplatelet treatment regimens (ticagrelor 2x90 mg, ticagrelor 2x60 mg, ticagrelor 2x45 mg or clopidogrel 75 mg [morning]+placebo [evening]) or placebo and will be assessed for dyspnea at the day 7, then undergo a switch of treatment and reassessment at day 14. The sample size will be estimated based on preceding pilot studies. Discussion: The PREDATOR LD is expected to prospectively assess dyspnea rate with a loading dose of ticagrelor, and analyze a potential of theophylline to elevate symptoms of ticagrelor-induced dyspnea, while the PREDATOR MD will prospectively assess dyspnea and adverse events rate with a maintenance dose of P2Y12 inhibitors prospectively assess. All evaluations will be conducted using standardized metrics for dyspnea quantification.