PCI With GDMT Versus GDMT Alone for Patients With Ischemic Cardiomyopathy and Reduced LVEF (PCI-GULF)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Heart Failure With Reduced Ejection Fraction; Stable GDMT
• Intervention / Treatment: Procedure: Percutaneous coronary intervention; Drug: Guideline-directed medical therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 1154
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shao-Liang Chen, MD; Phone Number: +86-25-52271351; Email: chmengx@126.com
• Study Contact Backup: Name: Jing Kan, PhD; Phone Number: +86-25-52279862; Email: kanjingok@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital, Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GDMT only; The control group will receive GDMT; this is approved treatments for preventing HF that could be utilised as a comparator. All patients will be treated according to local guidelines on standard of care treatment for patients with HFrEF and post PCI, focusing on treatment of HF symptoms (e.g. diuretics) and comorbidities (including treatment for high blood pressure, ischaemic heart disease).	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 estimated glomerular filtration rate (eGFR) drop > 30 % or serum potassium >5.2 mmol/L.; Other Names: GDMT
Active Comparator: PCI with contemporary DES + GDMT; 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 two arms. 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.	Procedure: Percutaneous coronary intervention; PCI will be performed according to standard techniques. Use of a contemporary, FDA/CE-approved drug-eluting stent is mandatory.; Other Names: PCI; 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 estimated glomerular filtration rate (eGFR) drop > 30 % or serum potassium >5.2 mmol/L.; Other Names: GDMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACE)	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.	From randomization to the time when the last enrolled patient reaches 12-month follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cardiovascular death plus myocardial infarction and revascularization	This endpoint measures the time to first occurrence of any component of the composite of cardiovascular death, myocardial infarction, or unplanned ischemia-driven revascularization.	The last patient reaches the 12-month follow-up
Rate of cardiovascular death	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.	The last patient reaches the 12-month follow-up
Rate of myocardial infarction	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.	The last patient reaches the 12-month follow-up period
Rate of any unplanned revascularization	Unplanned revascularization includes all coronary revascularization procedures (PCI/CABG) performed during the study.	The last patient reaches the 12-month follow-up period
Rate of heart failure-related rehospitalization	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.	The last patient reaches the 12-month follow-up period
Incidence of device implantation procedure	Device implants include valve therapy, pacemakers or left ventricular assistive devices.	The last patient reaches the 12-month follow-up period
Heart transplantation	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.	The last patient reaches the 12-month follow-up period
Rate of worsening heart failure	worsening HF including intravenous medications in outpatients.	The last patient reaches the 12-month follow-up period
All-cause mortality	All-cause mortality refers to the death of a participant from any cause during the study period.	The last patient reaches the 12-month follow-up period
Change in LVEF	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.	The last patient reaches the 12-month follow-up period
Change from baseline in NT-proBNP concentration at 12 months	Change in NT-proBNP refers to the absolute or relative difference in NT-proBNP measured from randomization to the 12-month follow-up period.	The last patient reaches the 12-month follow-up period
Total number of (first and recurrent) MACE	heart failure and cardiovascular death will be combined to report heart failure-related health status.	The last patient reaches the 12-month follow-up period
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ)	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.	The last patient reaches the 12-month follow-up period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of contrast-associated acute kidney injury	Contrast-associated acute kidney injury (CA-AKI), defined according to the PC-AKI criteria as an increase in serum creatinine by ≥26.5 μmol/L or to ≥1.5 times the baseline level within 48 hours after contrast administration.	Within 48 hours after contrast administration
Rate of Stroke	Rate of stroke refers to the frequency of new, acute cerebrovascular events occurring in a study population.	The last patient reaches the 12-month follow-up period
Rate of Major bleeding	Major bleeding is defined as bleeding at BAR 3 grade or above.	The last patient reaches the 12-month follow-up period

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Investigators: Principal Investigator: Shao-Liang Chen, MD, Nanjing First Hospital, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2026
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PCI; HFrEF; MACE; GDMT
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease; Surgical Procedures, Operative; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Minimally Invasive Surgical Procedures; Percutaneous Coronary Intervention
• Other Study ID Numbers: KY20251223-09; BE2019615 (Other Grant/Funding Number: the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes