International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease - ISCHEMIA-CKD

Sep 06, 2022
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Presenter/Author:
Sripal Bangalore, MBBS, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Heart, Lung, and Blood Institute
Date Presented:
08/29/2022
Date Published:
03/30/2020
Date Updated:
09/06/2022
Original Posted Date:
11/16/2019
References

Contribution To Literature:

Highlighted text has been updated as of September 6, 2022.

The ISCHEMIA-CKD trial failed to show that routine invasive therapy was associated with a reduction in death/myocardial infarction vs. medical therapy among stable patients with moderate ischemia and chronic kidney disease.

Description:

The goal of the trial was to evaluate routine invasive therapy compared with optimal medical therapy among patients with stable ischemic heart disease, moderate to severe myocardial ischemia on noninvasive stress testing, and advanced chronic kidney disease.

Study Design

  • Randomized
  • Parallel

Patients with stable ischemic heart disease, moderate to severe ischemia, and chronic kidney disease were randomized to routine invasive therapy (n = 388) versus medical therapy (n = 389).

In the routine invasive therapy group, subjects underwent coronary angiography and percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) as appropriate.

In the medical therapy groups, subjects underwent coronary angiography only for failure of medical therapy.

  • Total number of enrollees: 777
  • Duration of follow-up: 2.3 years
  • Mean patient age: 63 years
  • Percentage female: 31%
  • Percentage with diabetes: 57%

Inclusion criteria:

  • Patients >20 years of age
  • Moderate to severe ischemia on noninvasive stress testing (nuclear ≥10% ischemia; echo ≥3 segments of ischemia; cardiac magnetic resonance ≥12% ischemia and/or ≥3 segments with ischemia; exercise treadmill test ≥1.5 mm ST depression in ≥2 leads or ≥2 mm ST depression in single lead at <7 METs with angina)

Exclusion criteria:

  • Recent acute coronary syndrome
  • Left ventricular ejection fraction <35%
  • Unacceptable angina at baseline
  • New York Heart Association class III-IV heart failure
  • Prior PCI or CABG within the last year

Angina frequency at baseline:

  • None, 50%
  • Several times per month, 38%
  • Daily/weekly, 12%

Other salient features/characteristics:

  • Over the entire follow-up period, cardiac catheterization was performed in 85% of the invasive group vs. 22% of the medical therapy group
  • Over the entire follow-up period, coronary revascularization was performed in 50% of the invasive group vs. 12% of the medical therapy group

Principal Findings:

The primary outcome, death or myocardial infarction at 2.3 years, occurred in 36.4% of the routine invasive group compared with 36.7% of the medical therapy group (p = 0.95).

  • Among those with severe ischemia: (invasive/medical therapy hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.46-1.05)
  • Among those with moderate ischemia: (invasive/medical therapy HR 1.30, 95% CI 0.94-1.79; p for interaction = 0.02)

Secondary outcomes:

  • Death, myocardial infarction, hospitalization for unstable angina or heart failure, or resuscitated cardiac arrest: 38.5% of the routine invasive group compared with 39.7% of the medical therapy group (p = 0.93)
  • All-cause death: 27.8% of the routine invasive group compared with 27.2% of the medical therapy group (p = 0.91)
  • Periprocedural myocardial infarction: (invasive/conservative HR 2.03, 95% CI 0.59-7.01)
  • Spontaneous myocardial infarction: (invasive/conservative HR 0.72, 95% CI 0.47-1.09)
  • Stroke: (invasive/conservative HR 3.76, 95% CI 1.52-9.32)
  • Death or dialysis: (invasive/conservative HR 1.48, 95% CI 1.04-2.11)
  • Dialysis <30 days after procedure: 2.1% of the routine invasive group compared with 0.6% of the medical therapy group (p = 0.13)

Quality of life outcomes:

  • Seattle Angina Questionnaire (SAQ) summary score at 3 months for invasive vs. conservative therapy:
    • 2.1 points (95% credible interval -0.4 to 4.6) overall
    • 10.1 points (95% credible interval 0.0 to 19.9) daily/weekly angina at baseline
    • 2.2 points (95% credible interval -2.0 to 6.2) monthly angina at baseline
    • 0.6 points (95% credible interval -1.9 to 3.3) no angina at baseline
  • At 12 and 36 months, there was no longer any benefit on SAQ summary score for invasive vs. conservative therapy

Clinical outcomes across the spectrum of kidney function:

  • The primary outcome (death or myocardial infarction) was increased among those with advanced kidney disease (p < 0.001). Bleeding was also increased among those with advanced kidney disease.
  • The invasive vs. conservative relationship on death or myocardial infarction was the same regardless of chronic kidney disease stage (p for interaction = 0.47) or estimated glomerular filtration rate (p for interaction = 0.69).

5-year follow-up:

  • All-cause mortality: 40.6% in the routine invasive group compared with 37.4% in the medical therapy group (p = 0.32)
  • Cardiovascular mortality: 29.0% in the routine invasive group compared with 27.1% in the medical therapy group (p = 0.75)

Interpretation:

Among patients with stable ischemic heart disease, moderate to severe ischemia on noninvasive stress testing and advanced chronic kidney disease, routine invasive therapy failed to reduce the incidence of death or myocardial infarction compared with optimal medical therapy. There was also no benefit from invasive therapy regarding all-cause mortality with 5 years of follow-up. In fact, invasive therapy was associated with an increased hazard for stroke and death/dialysis compared with conservative therapy.

There was a large proportion of subjects with no angina at baseline. There was a modest improvement in symptom benefit at 3 months, especially among those with daily/weekly angina; however, this benefit dissipated at all later time points. These results do not apply to patients with current/recent acute coronary syndrome, highly symptomatic patients, or left ventricular ejection fraction <35%. Overall, mortality was high and not impacted (positively or negatively) by routine invasive therapy.

References:

Presented by Dr. Sripal Bangalore at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 29, 2022.

Bangalore S, Maron DJ, O’Brien SM, et al., on behalf of the ISCHEMIA-CKD Research Group. Management of Coronary Disease in Patients With Advanced Kidney Disease. N Engl J Med 2020;382:1608-18.

Spertus JA, Jones PG, Maron DJ, et al., on behalf of the ISCHEMIA-CKD Research Group. Health Status After Invasive or Conservative Care in Coronary and Advanced Kidney Disease. N Engl J Med 2020;382:1619-28.

Presented by Dr. Sripal Bangalore at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 29, 2020.

Presented by Sripal Bangalore at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019.

Presented by John A. Spertus at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019 (quality of life outcomes).

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: acc20, ACC Annual Scientific Session, AHA Annual Scientific Sessions, AHA19, Acute Coronary Syndrome, Angina Pectoris, Angina, Unstable, Cardiac Catheterization, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, ESC22, ESC Congress, Exercise Test, Heart Arrest, Heart Failure, Kidney Diseases, Magnetic Resonance Imaging, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Percutaneous Coronary Intervention, Renal Dialysis, Renal Insufficiency, Chronic, Secondary Prevention, Stroke, Stroke Volume


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