International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 5,391
- 主要终点
- Cumulative Event Rate of Death: All-Cause
研究概览
简要总结
The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up (ISCHEMIA-EXTEND) is the long-term follow-up of randomized, surviving participants in ISCHEMIA. ISCHEMIA was an NHLBI-supported trial that randomized 5,179 participants with stable ischemic heart disease to two different management strategies: 1) an initial invasive strategy (INV) of cardiac catheterization and revascularization when feasible plus guideline-directed medical therapy (GDMT), or 2) an initial conservative strategy (CON) of GDMT. The trial did not demonstrate a reduction in the primary endpoint with an initial invasive strategy. There was an excess of procedural myocardial infarction (MI) and a reduction in spontaneous MI in the INV group. Prior evidence suggests that spontaneous MI carries a higher risk of subsequent death than procedural MI. There was a late separation in the cardiovascular (CV) mortality curves over a median of 3.2 years follow-up in ISCHEMIA. The MI incidence curves crossed at approximately 2 years. However, during the trial follow-up phase there were excess non-CV deaths in the invasive strategy. Therefore, it is imperative to ascertain long-term vital status to provide patients and clinicians with robust evidence on whether there are differences between management strategies and to increase precision around the treatment effect estimates for risk of all-cause, CV and non-CV death over the long-term.
Overarching Goal:
To assess the effect of an initial invasive strategy on long-term all-cause, CV and non-CV mortality compared with an initial conservative strategy in SIHD patients with at least moderate ischemia on stress testing, over 10 years median follow-up.
Condition: Coronary Disease Procedure: Observational Phase: Phase III per NIH Condition: Cardiovascular Diseases Procedure: Observational Phase: Phase III per NIH Condition: Heart Diseases Procedure: Observational Phase: Phase III per NIH
详细描述
The primary goals of all therapies are to enable patients to feel better and/or live longer. ISCHEMIA provided definitive data on the benefit of INV on quality of life. However, mortality is the most objective and compelling clinical outcome. Strategies that reduce deaths over the long term are of greatest interest to patients and physicians. Long-term follow-up of the ISCHEMIA trial cohort to assess all-cause, CV and non-CV mortality by treatment group is particularly important given that the primary results show relatively late crossing of the event curves, an overall reduction in spontaneous MI with INV, and late divergence of CV death curves in favor of the INV strategy but with an excess of non-CV deaths.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL:
The investigators will conduct a long-term ascertainment of all-cause, CV and non-CV mortality for surviving ISCHEMIA participants. The limited follow-up after the observed reduction in spontaneous MI events may not have been long enough to observe a mortality benefit, and this makes it imperative to assess long-term all-cause, CV and non-CV mortality to determine whether an initial invasive strategy reduces the risk of death years later, as seen in other trials with crossing curves, e.g., STICH, a randomized trial comparing a strategy of surgical revascularization to GDMT alone in patients with SIHD and LVEF <35%.
Furthermore, with additional accrual of deaths, the investigators will provide estimates on the impact of INV in the highest risk subgroup, those with coronary artery anatomy for whom practice guidelines have recommended CABG to improve survival (3-vessel CAD and 2-vessel CAD with proximal LAD stenosis). Equally important is to improve precision around the point estimates of the treatment effect for all-cause, CV and non-CV mortality for the trial overall and in important subgroups to efficiently maximize the substantial investment by of NHLBI, patients, and study teams.
Vital status data will be collected in a rigorous manner from high-quality vital statistics registries, medical records, or by contacting participants and their next of kin.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Alive at the end of the initial follow-up period for ISCHEMIA
排除标准
- •Participants who withdrew consent during initial trial phase
- •Participants who declined participation in long-term follow-up
研究组 & 干预措施
Active Comparator: Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
干预措施: cardiac catheterization (Procedure)
Active Comparator: Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
干预措施: coronary artery bypass graft surgery (Procedure)
Active Comparator: Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
干预措施: percutaneous coronary intervention (Procedure)
Active Comparator: Conservative Strategy
Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms.
干预措施: Lifestyle (Behavioral)
Active Comparator: Conservative Strategy
Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms.
干预措施: Medication (Drug)
结局指标
主要结局
Cumulative Event Rate of Death: All-Cause
时间窗: Year 10 (Range: 6-13 years)
Cumulative event rate of death from all causes.
Cumulative Event Rate of Cardiovascular (CV) Death
时间窗: Year 10 (Range 6-13 years)
Cumulative event rate of death from cardiovascular causes.
Cumulative Event Rate of Non-CV Death
时间窗: Year 10 (Range: 6-13 years)
Cumulative event rate of death from non-cardiovascular causes.
次要结局
- Cumulative Event Rate of Death by High Risk Subgroups(Year 10 (Range 6-13 years))