PCI With GDMT Versus GDMT Alone for Patients With Ischemic Cardiomyopathy and Reduced LVEF

Official title

Percutaneous Coronary Intervention With Guideline-Directed Medical Therapy Versus Guideline-Directed Medical Therapy Alone for Patients With Ischemic Cardiomyopathy and Reduced Left Ventricular Ejection Fraction: A Randomized, Controlled, Open-Label, Multicenter PCI-GULF Trial

Overview

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

• Procedure Percutaneous coronary intervention
  PCI will be performed according to standard techniques. Use of a contemporary, FDA/CE-approved drug-eluting stent is mandatory.
• Drug Guideline-directed medical therapy
  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 estimate

Primary outcome measures

• Major adverse cardiovascular events (MACE) [Time frame: From randomization to the time when the last enrolled patient reaches 12-month follow-up.]

Secondary outcome measures (12)

• Rate of cardiovascular death plus myocardial infarction and revascularization [Time frame: The last patient reaches the 12-month follow-up]
• Rate of cardiovascular death [Time frame: The last patient reaches the 12-month follow-up]
• Rate of myocardial infarction [Time frame: The last patient reaches the 12-month follow-up period]
• Rate of any unplanned revascularization [Time frame: The last patient reaches the 12-month follow-up period]
• Rate of heart failure-related rehospitalization [Time frame: The last patient reaches the 12-month follow-up period]
• Incidence of device implantation procedure [Time frame: The last patient reaches the 12-month follow-up period]
• Heart transplantation [Time frame: The last patient reaches the 12-month follow-up period]
• Rate of worsening heart failure [Time frame: The last patient reaches the 12-month follow-up period]
• All-cause mortality [Time frame: The last patient reaches the 12-month follow-up period]
• Change in LVEF [Time frame: The last patient reaches the 12-month follow-up period]
• Change from baseline in NT-proBNP concentration at 12 months [Time frame: The last patient reaches the 12-month follow-up period]
• Total number of (first and recurrent) MACE [Time frame: The last patient reaches the 12-month follow-up period]

Eligibility criteria

Inclusion criteria

• Age ≥18 years at screening.
• Documented LVEF ≤40% assessed by quantitative transthoracic echocardiography confirmed at the core laboratory within 90 days prior to randomization.
• 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.
• 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.
• On stable GDMT for at least 4 weeks prior to randomization under the advisor's assessment at each site.
• 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

• Class III or IV angina requiring revascularization.
• Any unplanned hospitalization within 30 days.
• Any PCI within 12 months.
• Any prior CABG.
• Cardiogenic shock or end-stage heart failure (NYHA class IVb - unable to ambulate)
• Non-cardiac life expectancy <1 year at screening (e.g., malignancy, advanced liver disease).
• Coronary anatomy requiring surgical revascularization by local heart team determination.
• Coronary anatomy unsuitable for PCI.
• HF due to specific cardiomyopathies, including restrictive/infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic obstructive cardiomyopathy (HOCM).
• Severe stenosis or regurgitation of any heart valve.
• Contraindication to dual antiplatelet therapy or iodinated contrast.
• 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.
• Participation in another interventional trial that may interfere with the PCI and GDMT as specified in this protocol.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Nanjing First Hospital, Nanjing Medical University — Nanjing

Identifiers

NCT: NCT07349979 · KY20251223-09 · BE2019615

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗