Coronary Artery Disease, Heart Failure With Reduced Ejection Fraction, Stable GDMT
Conditions
Keywords
HFrEF, PCI, GDMT, MACE
Brief summary
To evaluate whether percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) combined with guideline-directed medical therapy (GDMT), compared to GDMT alone, reduces the time to first occurrence of major adverse cardiovascular events (MACE) during a median follow-up of at least 24 months, measured at the time the last enrolled patient reaches 12 months, in patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤40%. MACE is a composite of cardiovascular \[CV\] death, myocardial infarction (MI), heart failure (HF) related rehospitalization, heart transplantation, requirement for durable left ventricular assist device \[LVAD\] implantation, or worsening heart failure treated as an out-patient requiring treatment with intravenous medications.
Detailed description
A prospective, randomized, controlled, open-label, multicenter trial with blinded endpoint adjudication (PROBE design) A total of 1154 patients with LVEF ≤40%, angiographically proven coronary artery disease (CAD) amenable to PCI, and symptomatic heart failure (NYHA Class II-IV) on stable GDMT，will be assigned at 1:1 ratio to: Experimental Group: PCI with contemporary DES + GDMT. Control Group: GDMT alone. Angiographically proven CAD is defined as 1) a visually estimated diameter stenosis (DS) of ≥90%, or 2) a chronic total occlusion with a high likelihood (\>80%) of PCI success, or 3) a visually estimated diameter stenosis (DS) of \<90%, or 4) a ≥50% left main stenosis, with conditions 3) and 4) both requiring a QFR ≤0.80, and all planned PCI lesions are considered amenable to PCI with DES by an interventional cardiologist. Randomization will be stratified by the presence of planned CTO PCI, planned left main PCI and center. Complete revascularization of all angiographically significant lesions is encouraged, to be performed either during the index procedure or within a staged procedure within 30 days. However, it is recommended that chronic total occlusions are only treated if they supply viable myocardium (preserved regional wall motion or viability by cardiac MR or PET). All PCIs in any lesion with reference vessel diameter ≥2.5 mm MUST be guided by intravascular imaging (IVUS or OCT). The use of mechanical circulatory system (including IABP, Impella, or ECMO) is left at operator's discretion. Drug-coated balloon (DCB) alone is not recommended, but the combination of DES with DCB (e.g. for diffuse distal disease or side branch treatment of a bifurcation lesion) is left to operator's discretion. Both arms receive optimized GDMT according to current guidelines. Given the nature of the intervention (PCI vs. no PCI), treating physicians and patients cannot be blinded. To minimize bias, a PROBE design is employed with a blinded independent Clinical Events Committee (CEC), blinded core laboratories, and blinded statisticians. The catheterization laboratory team is unblinded but not involved in follow-up decisions or endpoint assessments. Clinic/telephone follow-up is conducted at 30 days, 3, 6, 9, 12 months and then yearly until the time that the last patient enrolled has reached 12-month follow-up. In addition, at this time, a final "sweep" visit (phone call) will be made to all patients who have not had a follow-up completed within 30 days. All subjects in both groups receive evidence based GDMT and dual antiplatelet therapy (DAPT) per guidelines throughout the study.
Interventions
PROCEDUREPercutaneous coronary intervention
PCI will be performed according to standard techniques. Use of a contemporary, FDA/CE-approved drug-eluting stent is mandatory.
GDMT optimization follows a structured titration algorithm: Week 0: introducing angiotensin-converting enzyme inhibitor (ACEi)/ angiotensin II receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI) and beta-blockers. Week 1: adding mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Adjust every 2-4 weeks to reach target or tolerable dose unless symptomatic hypotension (systolic blood pressure \[SBP\] \< 90 mmHg) or estimated glomerular filtration rate (eGFR) drop \> 30 % or serum potassium \>5.2 mmol/L.
Sponsors
Nanjing First Hospital, Nanjing Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
Given the nature of the intervention (PCI vs. no PCI), treating physicians and patients cannot be blinded. To minimize bias, a PROBE design is employed with a blinded independent Clinical Events Committee (CEC), blinded core laboratories, and blinded statisticians. The catheterization laboratory team is unblinded but not involved in follow-up decisions or endpoint assessments.
Intervention model description
PCI with DES plus GDMT versus GDMT alone
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years at screening. 2. Documented LVEF ≤40% assessed by quantitative transthoracic echocardiography confirmed at the core laboratory within 90 days prior to randomization. 3. Symptomatic heart failure (NYHA Functional Class II, III, or ambulatory Class IVa) or hospitalization for heart failure within the prior 12 months or NT-proBNP ≥600 pg/mL. 4. Angiographically proven CAD with at least one lesion with 1) a visually estimated diameter stenosis (DS) of ≥90% or 2) chronic total occlusion with a high likelihood (\>80%) of PCI success, or 3) a visually estimated DS of \<90%, or 4) a ≥50% left main stenosis, with conditions 3) and 4) both requiring a QFR ≤0.80, and all planned PCI lesions considered amenable to PCI with DES by an interventional cardiologist. 5. On stable GDMT for at least 4 weeks prior to randomization under the advisor's assessment at each site. 6. The subject, or their legal guardian, has a clear understanding of the trial's design and procedures, provide written informed consent, and is able to comply with all follow-up procedures.
Exclusion criteria
1. Class III or IV angina requiring revascularization. 2. Any unplanned hospitalization within 30 days. 3. Any PCI within 12 months. 4. Any prior CABG. 5. Cardiogenic shock or end-stage heart failure (NYHA class IVb - unable to ambulate) 6. Non-cardiac life expectancy \<1 year at screening (e.g., malignancy, advanced liver disease). 7. Coronary anatomy requiring surgical revascularization by local heart team determination. 8. Coronary anatomy unsuitable for PCI. 9. HF due to specific cardiomyopathies, including restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic obstructive cardiomyopathy (HOCM). 10. Severe stenosis or regurgitation of any heart valve. 11. Contraindication to dual antiplatelet therapy or iodinated contrast. 12. Pregnancy, lactation, or women of childbearing potential not using effective contraception. A negative urine pregnancy test is required within 7 days prior to randomization for women of childbearing potential. 13. Participation in another interventional trial that may interfere with the PCI and GDMT as specified in this protocol. 14. Any other circumstances that the investigator deems inappropriate for participation, including but not limited to conditions that may jeopardize patient safety, confound data interpretation, or patients unlikely to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular events (MACE) | From randomization to the time when the last enrolled patient reaches 12-month follow-up. | MACE is a composite of cardiovascular \[CV\] death, myocardial infarction, HF-related rehospitalization, heart transplantation, requirement for durable LVAD, or worsening heart failure treated as an out-patient requiring treatment with intravenous medications (out-patient worsening HF) through a median of at least 24-month follow-up, measured at the time the last enrolled patient reaches 12-month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of cardiovascular death plus myocardial infarction and revascularization | The last patient reaches the 12-month follow-up | This endpoint measures the time to first occurrence of any component of the composite of cardiovascular death, myocardial infarction, or unplanned ischemia-driven revascularization. |
| Rate of cardiovascular death | The last patient reaches the 12-month follow-up | A death that is primarily caused by a cardiovascular event or condition. This includes deaths resulting from acute myocardial infarction, stroke, heart failure, arrhythmias, and other cardiovascular diseases. |
| Rate of myocardial infarction | The last patient reaches the 12-month follow-up period | The diagnosis of an myocardial infarction should be made according to standard clinical practice but is expected to align with the criteria from Fourth Universal Definition of MI, i.e. detection of a rise and/or fall of cardiac biomarkers such as troponin and at least one of the following: typical clinical symptoms, ischaemic ECG findings, imaging evidence of myocardial injury, or detection of an intracoronary thrombus by angiography or autopsy. |
| Rate of any unplanned revascularization | The last patient reaches the 12-month follow-up period | Unplanned revascularization includes all coronary revascularization procedures (PCI/CABG) performed during the study. |
| Rate of heart failure-related rehospitalization | The last patient reaches the 12-month follow-up period | Heart failure readmission is defined as a hospitalization or extended emergency visit due to acute worsening of heart failure, requiring all of the following: a primary HF diagnosis, symptom deterioration, objective evidence of worsening, and intensified HF-specific therapy. |
| Incidence of device implantation procedure | The last patient reaches the 12-month follow-up period | Device implants include valve therapy, pacemakers or left ventricular assistive devices. |
| Heart transplantation | The last patient reaches the 12-month follow-up period | Rate of heart transplantation refers to the frequency at which patients in a study undergo surgical replacement of their native heart with a donor heart. |
| Rate of worsening heart failure | The last patient reaches the 12-month follow-up period | worsening HF including intravenous medications in outpatients. |
| All-cause mortality | The last patient reaches the 12-month follow-up period | All-cause mortality refers to the death of a participant from any cause during the study period. |
| Change in LVEF | The last patient reaches the 12-month follow-up period | Change in LVEF refers to the absolute or relative difference in Left Ventricular Ejection Fraction measured from randomization to the 12-month follow-up period. |
| Change from baseline in NT-proBNP concentration at 12 months | The last patient reaches the 12-month follow-up period | Change in NT-proBNP refers to the absolute or relative difference in NT-proBNP measured from randomization to the 12-month follow-up period. |
| Total number of (first and recurrent) MACE | The last patient reaches the 12-month follow-up period | heart failure and cardiovascular death will be combined to report heart failure-related health status. |
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) | The last patient reaches the 12-month follow-up period | The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) is a percentage-based health index ranging from 0 to 100, where higher scores indicate better heart failure-related health status. |
Countries
China
Contacts
CONTACTShao-Liang Chen, MD
CONTACTJing Kan, PhD
PRINCIPAL_INVESTIGATORShao-Liang Chen, MD
Nanjing First Hospital, Nanjing Medical University
Outcome results
None listed