Preoperative vs Postoperative Revascularization in Coronary Heart Disease Patients Undergoing Time-Sensitive Non-Cardiac Surgery (CHRONOS-PCI)

• Study overview This study is a prospective, open-label, randomized, multicenter trial to evaluate the safety and efficacy of preoperative versus postoperative revascularization strategies in patients with coronary heart disease undergoing time-sensitive non-cardiac surgery.

The primary hypothesis is that the postoperative (surgery-first) revascularization strategy will show a non-inferior rate of major adverse cardiovascular events (MACE) at 180 days after randomization compared with the preoperative (revascularization-first) strategy.

• Study population and sample size calculation Based on previous data, the 180-day incidence of MACE was approximately 5.5% in patients undergoing postoperative revascularization and 5.7% in those undergoing preoperative revascularization. Using a non-inferiority margin (delta) of 4%, a two-sided type I error rate (α) of 0.05, and a power of 78%, a total of 140 patients (70 in each group) will be enrolled. An attrition rate of 10% was considered.

• Primary endpoint: MACE at 180 days after randomization, defined as a composite of all-cause death, myocardial infarction, and any repeat revascularization.
• Design: Non-inferiority, delta = 4%.
• Sampling ratio: 1:1 (surgery-first vs. revascularization-first).
• Type I error (α): Two-sided 0.05.
• Accrual time: 3 years.
• Total time: 3.5 years (3 years accrual + 6 months follow-up).
• Assumption: MACE 5.5% vs. 5.7% in surgery-first and revascularization-first groups, respectively.
• Statistical power (1-β): 78%.
• Primary statistical method: Farrington-Manning non-inferiority test for binary outcomes.
• Potential withdrawal rates: 10%.
• Stratification in randomization: Randomization will be stratified according to (1) the estimated cardiovascular risk of the non-cardiac surgery and (2) the bleeding risk of the surgery.
• Research materials and treatment strategies

• Surgery-first group: Patients will undergo the time-sensitive non-cardiac surgery first. Coronary revascularization (PCI) will be performed after surgery.
• Revascularization-first group: Patients will undergo coronary revascularization (PCI) prior to the non-cardiac surgery, according to guideline-based recommendations and operator judgment.

Inclusion criteria

• Age ≥18 years
• Diagnosis of coronary heart disease with non-emergent indication for PCI confirmed by coronary angiography：

• Non-ST-elevation acute coronary syndrome (NSTE-ACS) at low or intermediate ischemic risk
• Chronic coronary syndrome (CCS) with one of the following anatomical characteristics (see Appendix 1 for definition):

• Moderate or severe stenosis of the left main coronary artery
• Multivessel disease involving the ostium of the left anterior descending artery
• Three-vessel disease with ≥70% stenosis in each major epicardial vessel
• Indication for time-sensitive non-cardiac surgery
• Planned non-cardiac surgery under general anesthesia in the following surgical departments: thoracic surgery, gastrointestinal surgery, colorectal surgery, hepatobiliary and pancreatic surgery, or gynecology
• For patients with malignant tumors requiring time-sensitive surgery: written informed consent confirming understanding and acceptance that, if randomized to the "PCI-first" group, their tumor surgery will be delayed until 90±14 days after PCI, with acknowledgement of potential risks (e.g., tumor progression, change in resectability)
• Ability to understand the study requirements and sign written informed consent in the language provided by the research team

Exclusion criteria

• Age >80 years
• Severe thrombocytopenia (platelet count <50×10⁹/L)
• Cardiogenic shock, severe heart failure (NYHA class IV, Killip class IV, or LVEF ≤35%), malignant arrhythmias (including cardiac arrest, asystole, ventricular fibrillation, or sustained ventricular tachycardia), or other life-threatening conditions requiring resuscitation
• Moderate-to-severe valvular heart disease, high-grade atrioventricular block, or other severe cardiac/pulmonary dysfunction incompatible with the planned surgery
• Planned surgery with extremely high bleeding risk (e.g., intracranial surgery, spinal surgery, retinal surgery)
• Patients with malignant tumors undergoing non-palliative surgery who are in poor general condition, defined as meeting any of the following:

• Karnofsky performance score <60
• Eastern Cooperative Oncology Group (ECOG) performance status >2
• Disease stage beyond surgical indications or estimated life expectancy <1 year
• Patients requiring emergency or urgent surgery due to critical illness
• Severe renal dysfunction: serum creatinine >442 μmol/L, GFR ≤30 mL/min/1.73 m², or currently on renal replacement therapy
• Severe hepatic dysfunction: Child-Pugh class C or higher
• Severe uncontrolled systemic infection
• Advanced dementia with significant decline in quality of life requiring full-time care and support
• Systemic thromboembolic disease (e.g., pulmonary embolism) making surgery unsuitable
• Women who are pregnant, breastfeeding, or planning pregnancy during the study period
• Severe, uncontrolled comorbid conditions continuously impairing physiological or psychological function
• Participation in another clinical study within 3 months prior to enrollment
• Any condition judged by the investigator to interfere with participation or study conduct