ISCHEMIA-CKD

Purpose: To evaluate clinical outcomes in the comparison of an initial invasive approach to conservative, optimal medical therapy (OMT) in CKD patients with SIHD and moderate or severe ischemia.

Trial Design: N=777, median age 63 years old; average 3.2 years follow-up. Randomized 1:1 to an initial invasive approach (cardiac catheterization and revascularization) + OMT to conservative, optimal medical therapy (OMT) alone in CKD patients with SIHD and moderate or severe ischemia.

Primary Composite Endpoint: Time to death, non-fatal MI.

Major Secondary Endpoint: Time to death, MI, hospitalization for unstable angina, heart failure or resuscitated cardiac arrest.

Composite Safety Outcome: Starting maintenance dialysis or death.

Results: In patients with CKD, SIHD and moderate or severe ischemia, the risk of adverse clinical outcomes with an initial invasive strategy was not reduced  compared to an initial conservative OMT strategy.

Primary Endpoints Results:

• Composite of death or nonfatal myocardial infarction (MI)
  • Initial invasive strategy 36.4%; conservative strategy 36.7% (HRadj 1.01 (0.79-1.29, p = 0.95)

Secondary Endpoints Results:

• Death, non-fatal MI, Hospitalization for Unstable Angina or Heart Failure or Resuscitated Cardiac Arrest
  • Initial invasive strategy 38.5%; conservative strategy 39.7% (HRadj 1.02 (0.79-1.29, p = 0.93)
• Death
  • Initial invasive strategy 27.2%; conservative strategy 27.8% (HRadj 1.03 (0.76-1.36, p = 0.91)
• Cardiovascular Death (invasive vs conservative strategy): HRadj 0.97 (0.71-1.33, p = 0.84)
• Myocardial infarction (invasive vs conservative strategy): HRadj 0.84 (0.57-1.25, p = 0.39)
• Procedural MI (invasive vs conservative strategy): HRadj 2.03 (0.59-7.01, p = 0.26)
• Spontaneous MI (invasive vs conservative strategy): HRadj 0.72 (0.47-1.09, p = 0.12)
• Unstable angina (invasive vs conservative strategy): HRadj 0.15 (0.02-1.37, p = 0.09)
• Heart Failure (invasive vs conservative strategy): HRadj 1.47 (0.69-3.12, p = 0.31
• Stroke (invasive vs conservative strategy): HRadj 3.76 (1.52-9.32, p = 0.004)

Safety Endpoints:

• Death or New Dialysis (invasive vs conservative strategy): HRadj 1.48 (1.04-2.11, p = 0.02)
• New Dialysis (invasive vs conservative strategy): HRadj 1.47 (0.88-2.44, p = 0.13)

Recommended:

• ISCHEMIA-CKD Abstract
• Sripal Bangalore's presentation slides (PDF)
• Discussant slides (PDF)

Related Science:

• The ISCHEMIA Study
• Planning and Conducting the ISCHEMIA Trial, Circulation 2018

Purpose

The purpose of the ISCHEMIA-CKD trial is to determine the best management strategy (initial invasive strategy versus conservative strategy) for patients with stable ischemic heart disease (SIHD), at least moderate inducible ischemia and advanced chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m² or on dialysis).

Trial Design

A randomized, open label, interventional clinical trial comparing invasive strategy with conservative strategy in patients with stable ischemic heart disease (SIHD), at least moderate inducible ischemia and advanced chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m² or on dialysis). Median follow-up 2.8 years.

Participants were assigned to two groups:

1. Initial invasive strategy- routine invasive strategy with cardiac catheterization followed by revascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft Surgery, if feasible) plus optimal medical therapy.
2. Conservative strategy- optimal medical therapy with cardiac catheterization and revascularization reserved for patients with OMT failure.

Trial Population:

• 777 participants (21 years and older) randomized in a 1:1 fashion to an invasive (388 patients) or a conservative strategy (389 patients)
• Median age was 63 years with 31% were women and 53% were on dialysis
• In those not on dialysis, 86% had CKD stage 4 and 14% had CKD stage 5 at baseline

Primary Endpoint(s)

• Composite of death or nonfatal myocardial infarction (MI)

Secondary Endpoint(s)

• Composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; and angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire (SAQ)
   
• Incidence of the composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure, resuscitated cardiac arrest, or stroke; composite of death, nonfatal MI, or stroke; composite endpoints incorporating cardiovascular death; composite endpoints incorporating other definitions of MI as defined in the clinical event charter; individual components of the primary and major secondary endpoints; stroke and health resource utilization, costs, and cost effectiveness.

Safety Outcomes

• Death or New Dialysis
• New Dialysis

Sponsor(s)

NYU Langone Health

New York University, National Heart, Lung, and Blood Institute (NHLBI), Duke University, Stanford University, Columbia University