Introduction: The management of acute myocardial injury following acute ischemic stroke (AMI-AIS), a frequent complication that severely worsens prognosis, is challenging. Remote ischemic conditioning (RIC) has demonstrated therapeutic potential in separate cardiac and cerebrovascular diseases, and preliminary single-center evidence suggests its safety and efficacy in patients with acute ischemic stroke (AIS) complicating acute myocardial infarction. Therefore, we propose to conduct a multicenter, randomized controlled trial to definitively evaluate the safety and efficacy of RIC in patients with AMI-AIS.

Methods: This is a multicenter, randomized, double-blind, sham-controlled trial of 580 participants with AMI-AIS. Participants will be randomized to receive either the RIC procedures or sham RIC procedures twice daily for 14 consecutive days. A 3-month follow-up will be conducted to assess the safety and efficacy of RIC in AMI-AIS patients. The primary study outcome is the incidence of major adverse cardio-cerebrovascular events (MACCEs). The secondary outcomes include mortality, neurological and cardiac function, cerebral infarct volume, and cerebral perfusion.

Inclusion Criteria:

1. Age ≥ 18 years, regardless of sex;
2. AIS confirmed by neuroimaging within 72 hours of symptom onset (or last known well time);
3. Acute myocardial injury confirmed by serial measurements of plasma cardiac troponin (cTn) within 72 hours of symptom onset [19];
4. Written informed consent provided by the participant or their legal authorized representative.

Exclusion Criteria:

1. Pre-stroke mRS score ≥ 2;
2. AIS patients receiving intravenous thrombolysis or endovascular thrombectomy;
3. Definite history of coronary heart disease, severe valvular heart disease, arrhythmia, heart failure, cardiomyopathy, elevated cTn, and abnormal electrocardiogram (ECG) before onset;
4. Suspicious cardiac-related symptoms (recurrent/persistent chest pain/chest tightness/palpitations, etc.) within 14 days before the index stroke;
5. Any disorder that could potentially lead to elevated pre-stroke cTn: sepsis, acute kidney injury, rhabdomyolysis, major cardiac surgery or myocardial infarction, previous ischemic or hemorrhagic stroke, congestive heart failure, pulmonary embolism, deep vein thrombosis, endocarditis, severe anemia, thyroid dysfunction, Drug application, etc.;
6. Patients who are planning for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for the index AMI within 3 months;
7. Severe liver or kidney dysfunction or malignant tumors;
8. Uncontrolled hypertension (systolic blood pressure ≥ 200mmHg at enrollment despite medication);
9. Any limb deformity, vascular or soft tissue injury, orthopedic trauma, or other conditions affecting the implementation of RIC;
10. Pregnancy or lactation period;
11. Patients with psychiatric disorders or other reasons unable to cooperate with treatment and follow-up.