Timing of Coronary Angiography in NSTEMI Complicated by Acute HF

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Immediate coronary angiography
  Immediate coronary angiography ≤2 hours after randomization
• Процедура Delayed coronary angiography
  Delayed coronary angiography after stabilization

Первичные конечные точки

• A cumulative incidence rate of all-cause death, non-fatal myocardial infarction (MI), or hospitalization for heart failure (HF) [Срок оценки: 1 year]

Вторичные конечные точки (12)

• A cumulative incidence rate of all-cause death, non-fatal MI, or hospitalization for HF [Срок оценки: 1, 6, 24, 36 months]
• All-cause death [Срок оценки: 1, 6, 12, 24, 36 months]
• Non-fatal MI [Срок оценки: 1, 6, 12, 24, 36 months]
• Hospitalization for HF [Срок оценки: 1, 6, 12, 24, 36 months]
• Cardiovascular death [Срок оценки: 1, 6, 12, 24, 36 months]
• Recurrent ischemia [Срок оценки: 1, 6, 12, 24, 36 months]
• All unplanned revascularization [Срок оценки: 1, 6, 12, 24, 36 months]
• Definite or probable stent thrombosis [Срок оценки: 1, 6, 12, 24, 36 months]
• Stroke [Срок оценки: 1, 6, 12, 24, 36 months]
• Major bleeding by Bleeding Academic Research Consortium [Срок оценки: 1, 6, 12, 24, 36 months]
• Acute kidney injury (AKI) and AKI requiring renal replacement therapy [Срок оценки: Up to 7 days]
• In-hospital death rate from any cause [Срок оценки: Up to 30 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 20 центров

• Gyeongsang National University Changwon Hospital — Changwon
• Keimyung University Dongsan Hospital — Daegu
• Kyungpook National University Hospital — Daegu
• Yeongnam University Medical Center — Daegu
• Chungnam National University Hospital — Daejeon
• Chonnam National University Hospital — Gwangju
• Gwangju Veterans Hospital — Gwangju
• Kwangju Christian Hospital — Gwangju
• … и ещё 12 центров

Идентификаторы

NCT: NCT07002164 · CNUH-2025-100

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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