Clinical trial NCT07002164: Timing of Coronary Angiography in NSTEMI Complicated by Acute HF
Official title: Trial of IMmediate Invasive Versus Delayed Coronary ANGiography in Non-ST-Segment Elevation Myocardial Infarction Complicated by Acute Decompensated Heart Failure: The TIMING-AHF Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Myocardial Infarction (MI)
Heart Failure
Keywords: Non-ST-segment elevation myocardial infarction
Acute decompensated heart failure
Coronary angiography
Timing
Lead sponsor: Chonnam National University Hospital
Sponsor class: OTHER
First posted: 2025-06-03
Enrollment: 780
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study objectives:

To determine the optimal timing of coronary angiography (CAG) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) complicated by acute decompensated heart failure (AHF). The primary objective of this trial is to test the hypothesis that immediate CAG ≤2 hours after establishment of NSTEMI diagnosis would result in a significant reduction in primary composite outcome of death from any cause, non-fatal myocardial infarction (MI), or hospitalization for heart failure (HF) at 12 months after randomization as compared with delayed CAG after stabilization.

Study hypothesis:

Immediate CAG ≤2 hours after establishment of NSTEMI diagnosis would result in a significant reduction in primary composite outcome of death from any cause, non-fatal myocardial infarction (MI), or hospitalization for heart failure (HF) at 12 months after randomization as compared with delayed CAG after stabilization.

Background:

Although current guidelines recommend early CAG within 2 hours for patients with NSTEMI complicated by AHF, many patients with NSTEMI complicated by AHF did not receive early CAG. However, no randomized clinical trials have evaluated the optimal timing of CAG in patients with NSTEMI complicated by AHF. Therefore, the investigators aimed to perform a prospective, investigator-initiated, open-label, muilticenter trial to compare the efficacy and safety between immediate CAG (CAG \<2 hours after establishment of NSTEMI diagnosis) and delayed CAG after stabilization (i.e. improved dyspnea and disappearance of pulmonary congestion) in participants with NSTEMI complicated by AHF.

Study procedure:

Following the establishment of NSTEMI diagnosis, participants fulfilling the eligibility criteria will be randomized at a ratio of 1:1 to immediate CAG ≤2 hours after randomization or delayed CAG after stabilization on another day during hospitalization.

Detailed description: Acute decompensated heart failure (AHF) is frequently encountered in patients with non-ST-segment elevation myocardial infarction (NSTEMI), and it is known to be associated with worse clinical outcomes that those without heart failure (HF). Although current guidelines recommend immediate invasive strategy for patients with NSTEMI complicated by AHF, its evidence is lack. It is difficult to decide whether to perform early coronary angiography (CAG) according to the guidelines in these high-risk patients due to the risk of procedural complications. Furthermore, the most of randomized trials regarding the timing of CAG in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have excluded these patients, therefore, there is lack of evidence for performing immediate CAG in such cases. In clinical practice, many patients with NSTEMI complicated by AHF did not receive early CAG. There are only two observational studies which investigated this issue. In the Korean nationwide registry data, a total of 1,027 patients with NSTEMI complicated by AHF were analyzed, and 14.5% among study population underwent early CAG within 2 hours according to the guidelines. All-cause mortality at 12 months was not significantly different irrespective of CAG timing. In other single-center study, early CAG \<24 hours was associated with a lower risk of adverse cardiac outcomes compared with delayed CAG ≥24 hours after admission.

Several studies have demonstrated improved clinical outcomes in high-risk patients with NSTE-ACS undergoing early CAG, whereas others have found no significant differences in clinical outcomes. Randomized clinical trials, such as SISCA, ISAR-COOL, RIDDLE-NSTEMI and EARLY, have demonstrated the advantages of early CAG compared to delayed invasive approach (i.e. CAG after stabilization) in high-risk patients with NSTE-ACS. The other trials regarding this issue have failed to show the superiority of early CAG over delayed invasive approach. However, no randomized clinical trials have evaluated the optimal timing of CAG in patients with NSTEMI complicated by AHF.

Therefore, the investigators aimed to perform a prospective, investigator-initiated, open-label, muilticenter trial to compare the efficacy and safety between immediate CAG (CAG \<2 hours after establishment of NSTEMI diagnosis) and delayed CAG after stabilization (i.e. improved dyspnea and disappearance of pulmonary congestion) in participants with NSTEMI complicated by AHF.

Eligibility criteria: Inclusion Criteria:

* Age ≥19 years
* Non-ST-segment elevation myocardial infarction
* New-onset or worsening of dyspnea (New York Heart Association class ≥2)
* Pulmonary congestion
* Patient's or guardian's consent after understanding the study

Exclusion Criteria:

* Cardiogenic shock at initial presentation
* ST-segment elevation myocardial infarction

  * ST-segment elevation ≥0.1 mV in at least 2 contiguous leads, or
  * New onset left bundle branch block
  * Posterior wall myocardial infarction
* Refractory angina
* Life threatening ventricular arrhythmias
* Life expectancy \<1 year
* Apparently non-ischemic cause of HF
* Pregnancy and lactation
* History of coronary artery bypass grafting (CABG), or planned CABG
* Patient's refusal to participate in study

Primary outcomes:
measure: A cumulative incidence rate of all-cause death, non-fatal myocardial infarction (MI), or hospitalization for heart failure (HF)
timeFrame: 1 year
Secondary outcomes:
measure: A cumulative incidence rate of all-cause death, non-fatal MI, or hospitalization for HF
timeFrame: 1, 6, 24, 36 months
measure: All-cause death
timeFrame: 1, 6, 12, 24, 36 months
measure: Non-fatal MI
timeFrame: 1, 6, 12, 24, 36 months
measure: Hospitalization for HF
timeFrame: 1, 6, 12, 24, 36 months
measure: Cardiovascular death
timeFrame: 1, 6, 12, 24, 36 months
measure: Recurrent ischemia
timeFrame: 1, 6, 12, 24, 36 months
measure: All unplanned revascularization
timeFrame: 1, 6, 12, 24, 36 months
measure: Definite or probable stent thrombosis
timeFrame: 1, 6, 12, 24, 36 months
measure: Stroke
timeFrame: 1, 6, 12, 24, 36 months
measure: Major bleeding by Bleeding Academic Research Consortium
timeFrame: 1, 6, 12, 24, 36 months
measure: Acute kidney injury (AKI) and AKI requiring renal replacement therapy
timeFrame: Up to 7 days
measure: In-hospital death rate from any cause
timeFrame: Up to 30 days
measure: In-hospital death rate from cardiovascular cause
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Changwon
country: Korea, Republic of
facility: Gyeongsang National University Changwon Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeongnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Gwangju Veterans Hospital
city: Gwangju
country: Korea, Republic of
facility: Kwangju Christian Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Koera University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Suncheon
country: Korea, Republic of
facility: St. Carollo General Hospital
city: Wonju
country: Korea, Republic of
facility: Yonsei University, Wonju Severance Christian Hospital
Study officials:
References: