The applicability of the results of the ISCHEMIA study to practical clinical practice in the US has been challenged by a new study showing that less than a third of US patients with stable ischemic heart disease (IHD) currently undergoing one Subject to intervention that meet study inclusion criteria.
The ISCHEMIA study, first reported in 2019, showed that in stable patients with moderate to severe ischemia, an invasive percutaneous coronary intervention (PCI) approach did not significantly reduce cardiovascular events after a median follow-up of 3.2 years. versus a conservative medical strategy.
For the current study, a group of intervention scientists analyzed recent US data on patients undergoing PCI and found that a large proportion of patients undergoing PCI for stable ischemic heart disease in the US met the ISCHEMIA criteria -Study population would not have met.
The study was published online on November 1st in JACC: Cardiovascular Interventions.
“Although ISCHEMIA was a very well-conducted study, our results show that it applies to only about one-third of stable IHD patients who underwent intervention in US real-world clinical practice. In this group, ISCHEMIA showed no reduction in event rate in the intervention group there was a reduction in symptoms, “lead author Saurav Chatterjee, MD, Long Island Jewish Medical Center, New York, told theheart.org | Medscape-Cardiology.
“But ISCHEMIA has not really answered the question about 67% of stable IHD in current US practice. We may be able to postpone PCI in these patients, but we don’t know from the ISCHEMIA trial as these patients were not included in the trial, “Chatterjee said.
“There is some concern that people will accept the results of ISCHEMIA as universal, but we cannot apply these results to all stable IHD patients currently undergoing intervention,” he added. “We believe that patients who are not part of the ISCHEMIA population need a differentiated, individual approach that takes into account symptom severity and patient preferences.”
In the new report, Chatterjee et al. notes that the applicability of the ISCHEMIA results to current practice has been questioned by some as a significant proportion of patients routinely considered for revascularization both inside and outside the United States have been excluded.
They point out that the ISCHEMIA study recruited 16.5% of participants from the United States and the proportion of patients in today’s US practice who would have qualified for the study is not clear.
They therefore examined the proportion of stable IHD patients who met the inclusion criteria for the ISCHEMIA study in a nationwide US PCI registry.
Researchers used data from the National Cardiovascular Data Registry’s (NCDR) CathPCI registry, which includes patients undergoing PCI in 1,662 facilities and who make up more than 90% of PCI-enabled hospitals in the United States.
All PCI procedures that were carried out from October 2017 to June 2019 at institutes participating in the NCDR CathPCI register were identified. Patients with acute coronary syndrome (ACS), cardiogenic shock, or cardiac arrest were excluded because there is significant evidence of revascularization in these groups and they were not included in the ISCHEMIA study.
Then all remaining stable IHD patients were divided into 1 of 4 groups.
ISCHEMIA-like: These patients had moderate or high risk findings on an exercise test, but no high-risk traits that would have excluded participation in the ISCHEMIA study
High risk: This group included patients with stable IHD and left ventricular ejection fraction of less than 35%, significant unprotected left main stenosis (> 50%), pre-existing dialysis, recent heart failure exacerbation, or heart transplant. These patients would have met the exclusion criteria for the ISCHEMIA study
Low risk: This group comprised patients with stable and negative or low-risk findings in the stress test and who would have met the exclusion criteria for the ISCHEMIA study
Unclassifiable: This group included patients with stable IHD who did not match any of the other cohorts, including no stress test or extent of ischemia not reported in stress tests. These patients would not have enough information to clearly meet the inclusion or exclusion criteria for the ISCHEMIA study
The results showed that 927,011 patients underwent PCI during the study period as recorded in the NCDR CathPCI registry. Of these, 58% had ACS, cardiogenic shock, or cardiac arrest and were excluded; the remaining 388,212 patients undergoing PCI for stable IHD formed the study population.
Of these, 125,302 (32.28%) had a moderate or high risk stress test with no high risk anatomical or clinical features and met the ISCHEMIA study inclusion criteria.
Of the stable IHD patients who did not meet the ISCHEMIA study inclusion criteria, 71,852 (18.51%) had high risk criteria that they would have excluded from the ISCHEMIA study, a total of 67,159 (17.29%) patients had low risk criteria who would have excluded them from the ISCHEMIA study, and 123,899 (31.92%) were unclassifiable, either due to lack of exercise testing or the extent of ischemia, which was not reported on exercise tests.
The authors suggest that the unclassifiable patients represent a “higher risk” population than those very similar to the ISCHEMIA study population, with more previous myocardial infarctions and heart failure.
ISCHEMIA investigators respond
In an accompanying editorial, ISCHEMIA researchers David J. Maron, MD, Stanford University School of Medicine, California, and Sripal Bangalore, MD, and Judith S. Hochman, MD, New York University Grossman School of Medicine, New York City, that many of the Chatterjee et al. Featured patients were excluded from the ISCHEMIA study for good reason.
They explain that ISCHEMIA was developed on the premise that previous stable IHD strategy studies such as COURAGE and BARI 2D included lower risk patients, and the remaining gap was the benefit of invasive management in patients at higher risk and moderate or severe stress to evaluate ischemia.
They indicate that of the NCDR patients with stable IHD in the current Chatterjee et al. Study who did not meet the ISCHEMIA entry criteria, 18.5% had high-risk traits, including 35.2% with left major artery disease of the coronary arteries, 43.7% with a left ventricular systolic dysfunction and 16.8% with end-stage renal failure.
Although ISCHEMIA results do not apply to patients excluded from the study, there is little controversy regarding the benefit of revascularization in patients with stable IHD with left ventricular coronary artery disease or left ventricular ejection fraction <35%, which is why they were excluded by ISCHEMIA, notice the editorials.
They also report that patients with end-stage renal disease who also failed to meet the inclusion criteria for ISCHEMIA were enrolled in the accompanying ISCHEMIA CKD study.
They also point out that at the other end of the risk spectrum, 17.3% of stable IHD patients in the current analysis had negative or low risk function tests and these patients were excluded from ISCHEMIA because they were not shown in COURAGE and BARI 2D by one Revascularization benefits and does not meet the guideline recommendations for elective PCI without symptoms.
Of the 31.9% of stable IHD patients who lacked data on ischemic exposure, the ISCHEMIA investigators say that some of them qualified for the study, although it is not possible to tell how many. They propose a conservative estimate of 50%.
Taking these arguments into account, the editors recalculated the proportion of NCDR-PCI patients with stable IHD who would have been included in ISCHEMIA at 62.1% to 68.6% of patients.
They say the current NCDR analysis by Chatterjee et al. At worst, it should be interpreted that the results of the ISCHEMIA study apply to only 32% of patients undergoing elective PCI in the United States, and at best, “the results apply to a far higher proportion, except just those with high risk (18.5%) or with unacceptable symptoms despite maximum drug therapy (proportion unknown), for which PCI is clearly indicated. “
The editors conclude: “The purpose of the Chatterjee et al. is to inform the cardiovascular community of the proportion of patients with stable IHD in clinical practice who would have been excluded from ISCHEMIA regardless of the logic of any exclusion criterion, this editorial is to provide a context for the analysis, admittedly from the View from ISCHEMIA investigators in the hope that this will help readers clearly understand the relevance of the study to the patients they are caring for. “
They add: “For practical and ethical reasons, ISCHEMIA excluded stable patients with high-risk characteristics, drug-poorly controlled angina, and low-risk characteristics who did not meet the evidence-based guidelines for revascularization for whom the ISCHEMIA study is highly relevant; exactly what percentage is based on the NCDR data is difficult to say. “
The ISCHEMIA study was supported by the National Heart, Lung, and Blood Institute.
JACC: resume interventions. Published online November 1, 2021. Abstract, Editorial.
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