Aernoud Fiolet

103 The LoDoCo2 trial rationale, design, and baseline characteristics Safety measures of interest Safety measures include (1) neutropenia, defined as absolute neutrophil count <1500/μL (<1.5 × 109/L), (2) neuropathy, and (3) myotoxicity as evidenced by myositis or myopathy as classified by the European Consensus document. 35 End-point definitions Universal definitions have been used for CV death, myocardial infarction, and ischemic stroke. 36 Cardiovascular death is defined as any deathwith a clear relationship to underlying CV disease, including death secondary to acute myocardial infarction causing sudden death, or acute heart failure, a complication of a coronary revascularization procedure where the cause of death is clearly related to the procedure, death due to CV hemorrhage and death due to other CV causes. Death due to myocardial infarction refers to a death by any CV mechanism (e.g., arrhythmia, sudden death, heart failure, stroke, pulmonary embolus, peripheral arterial disease) ≤30 days after a myocardial infarction. Acute myocardial infarction is defined by the ACC/AHA/ESC 3rd universal definition of (acute) myocardial infarction. 37 Ischemia-driven coronary revascularization requires a history of new or accelerating ischemic symptoms without a rise in serum troponin together with angiographic evidence of a new culprit lesion and/or supporting clinical evidence of ischemia including fractional flow reserve and/or other forms of functional testing, which then leads to coronary revascularization. Ischemic stroke is defined as symptoms of acute focal cerebral, spinal, or retinal dysfunction due to a vascular cause with other non-vascular etiologies excluded. The symptoms must last >24 hours in the absence of brain imaging. The symptoms may last <24 hours in the presence of pathological, imaging or other objective evidence of acute, focal cerebral, spinal, or retinal ischemia or hemorrhage. Ischemic stroke requires pathological, imaging, or other objective evidence of acute, focal cerebral, spinal, or retinal ischemic injury in a defined vascular distribution; or clinical evidence of acute, focal cerebral spinal cord, or retinal ischemic injury based on symptoms persisting >24 hours or until death, and other etiologies excluded. Ischemic stroke includes hemorrhagic infarction but not intra- cerebral or subarachnoid hemorrhage. The primary outcome will therefore include atherosclerotic, cardio-embolic and lacunar stroke.