ISCHEMIA-CKD

International Study of Comparative Health Effectiveness With Medical and Invasive Approaches—Chronic Kidney Disease Trial

Trial Summarized By: Mohsin Chowdhury, MD | Reviewed/Approved by: Larry Allen, MD, MHS

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).

Key Findings

ISCHEMIA-CKD demonstrated that, among patients with stable ischemic heart disease and stage 4-5 chronic kidney disease (53% were on dialysis), an initial invasive strategy of cardiac catheterization did not lead to a reduction in clinical outcomes as compared with an initial conservative strategy (death or myocardial infarction: invasive 36.4%, conservative 36.7%, p=0.95). Notably, the trial excluded highly symptomatic patients and the invasive arm saw relatively low rates of coronary revascularization.



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Commentary



Results: ISCHEMIA-CKD trial with Sripal Bangalore

Sripal Bangalore, MD explains the results of the ISCHEMIA-CKD trial, in which researchers compared invasiver versus conservative treatment strategies for patients with at least moderate ischemia and advanced chronic kidney disease.

Dr. Bangalore is the director of research at the cardiac catheterization lab at NYU Langone Health.


Commentary: ISCHEMIA-CKD with Rasha Al-Lamee

Rasha Al-Lamee, MA, MBBS, PhD served as a moderator during the ISCHEMIA session. Here she comments on the Chronic Kidney Disease focus of the ISCHEMIA trial, presented at Scientific Sessions 2019.

Dr. Al-Lamee is on the faculty of the Medicine, National Heart & Lung Institute at Imperial College London.

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.

ISCHEMIA-CKD Data
  Invasive Conservative  
Primary EP 36.4% 36.7% HR 1.01
P=0.95
Secondary EP 38.5% 39.7% HR 1.01
P=0.93
Stroke     HR 3.76
P=0.004
Safety     HR 1.48
P=0.02

Detailed Results

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)

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Background

Among patients with advanced chronic kidney disease (CKD), cardiovascular disease is the leading cause of death. Yet, CKD patients are under-represented in contemporary trials of revascularization versus medical management for stable ischemic heart disease (SIHD). Patients with advanced CKD and cardiovascular disease are also often medically undertreated due to concern for medical related adverse events. Furthermore, participants with advanced CKD are at increased risk for short-term complications, including contrast-induced acute kidney injury (AKI), dialysis, major bleeding, and short-term risk of death. It is unknown if these short-term increased risks are offset by long-term benefits. The above has resulted in clinical equipoise in the management of these patients, with the rates of revascularization only around 10-45%.

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

Collaborator(s)

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

References and Sources:

Key Words
AHA Scientific Sessions, AHA2019, ischemia, stable coronary artery disease, chronic kidney disease, dialysis
Related clinical topics
Kidney Diseases, Chronic Renal Insufficiency, Chronic Kidney Failure, Coronary Artery Disease, Myocardial Ischemia, Heart Diseases, Ischemia, Cardiovascular Diseases, Urologic Diseases, Coronary Disease, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Renal Insufficiency, Pathologic Processes