Medical therapy

NEJM: Study compares PCI to medical therapy to reduce death or hospitalization from heart failure

NEJM: Study compares PCI to medical therapy to reduce death or hospitalization from heart failure

MedicalResearch.com Interview with:

Dr. Morgan

Dr. Holly Morgan MB, B.Ch.
Clinical Researcher and Investigator REVIVED
King’s College London

MedicalResearch.com: What is the background of this study?

Answer: Coronary artery disease is the most common cause of heart failure. While individually tailored pharmacological and device therapy (optimal medical therapy, OMT) is the cornerstone of the management of ischemic heart failure, the rates of death and hospitalization for heart failure remain unacceptably high in this population. . Given the causal relationship between coronary artery disease and heart failure, coronary revascularization has long been considered a treatment option for these patients. Although there is randomized evidence to support surgical revascularization with coronary artery bypass grafting (1), none previously existed for percutaneous coronary intervention (PCI) in stable ischemic left ventricular dysfunction. Despite this, patients are frequently offered PCI in this setting (particularly if they are unsuitable for surgery); motivated by the belief that the hibernating myocardium will improve its function if blood flow is restored, regardless of the method of revascularization. This approach was supported by some international guidelines, although the recommendations varied.

The REVIVED-BCIS2 trial aimed to establish whether revascularization with PCI in addition to OMT would improve event-free survival in patients with ischemic left ventricular dysfunction, compared to OMT alone (2). Inclusion criteria included left ventricular ejection fraction ≤ 35%, extensive coronary artery disease (British Cardiovascular Intervention Society risk score ≥ 6, indicating significant stenoses in the left main coronary artery, coronary artery proximal left anterior descending, dominant circumflex artery, disease in multiple vessels, or a combination thereof) and viability in at least four dysfunctional myocardial segments that were amenable to PCI. The main exclusion criteria were acute myocardial infarction within 4 weeks of randomisation, angina limiting the patient’s quality of life or decompensated heart failure or sustained ventricular arrhythmia within 72 hours.

The primary composite outcome was death from any cause or hospitalization for heart failure; the minimum follow-up was 24 months. Primary secondary outcomes included change in left ventricular ejection fraction from baseline to six- and twelve-month follow-up, myocardial infarction, unplanned revascularization, and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire and EQ-5D-5L.

MedicalResearch.com: What are the main findings?

Answer: REVIVED recruited 700 patients at 40 sites across the UK between 2013 and 2020. The median follow-up was 41 months. The groups were well matched in terms of baseline characteristics and constituted a comorbid population with approximately half with hypertension and 40% with diabetes. Half of the enrolled patients reported a previous clinical diagnosis of myocardial infarction. They had significant coronary artery disease with a median risk score of 10 and one in seven had left main stem disease. The majority of patients were in NYHA functional class I or II, but 25% were in functional class III.

The primary outcome occurred in 37.2% of the PCI group and 38.0% of the optimal medical treatment group (relative risk 0.99, p=0.96). No differential treatment effect was observed in any of the pre-specified subgroups. While LV ejection fraction improved over time, this was seen in both arms with no significant difference in improvement at any time point. The patient reported that quality of life scores improved in the PCI group, and although this difference was statistically significant at 6 and 12 months, at 24 months the OMT group had caught up and the mean difference in the Kansas City Cardiomyopathy Questionnaire summary score was only 2.6 points. (CI 0.4 – 8.1). Major bleeding occurred in 3.1% of the PCI group during the first 12 months and 0.6% in the OMT group, but there was no difference at 2 years.

MedicalResearch.com: What should readers take away from your report?

Answer: In patients with LV dysfunction, extensive coronary artery disease, and demonstrable myocardial viability, adding PCI to OMT did not reduce the incidence of death or hospitalization for heart failure. Additionally, PCI did not improve left ventricular ejection fraction, although a small improvement was noted in both groups. Therefore, patients who are diagnosed with heart failure and who have extensive coronary artery disease should not be treated with PCI. Patients who are candidates for bypass surgery should continue to be offered this treatment, consistent with the results of the STICH trial. Since patients with recent acute myocardial infarction and limiting angina were excluded from the trial, results should not be extrapolated to these patient populations, who should always be offered PCI for symptomatic reasons. . Although this is a high-risk comorbid population, PCI has been shown to be safe and should therefore be offered if other indications are present.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Answer: Further work is underway using the trial dataset to explore the remaining unanswered questions. It has been proposed that treatment with PCI may reduce the burden of ventricular arrhythmias in this population, a hypothesis that has not been tested in a randomized trial. Additionally, the REVIVED-BCIS2 results challenge the hibernation hypothesis (that restoring normal coronary perfusion through revascularization can improve left ventricular function and therefore clinical outcomes), as well as the routine use of myocardial viability testing to identify patients who might benefit from revascularization. Specific analyzes of viability studies performed for the trial may provide a better mechanistic understanding of why revascularization with PCI did not provide benefit, as well as rationalize the use of viability testing in this population. Given the difference between the populations of the trials included in REVIVED and STICH, randomized comparisons of treatments in patients eligible for surgical revascularization could be considered.

MedicalResearch.com: Is there anything else you would like to add? Revelations?

Answer: The trial team would like to thank all the patients who took part in the trial, all the NHS and research staff who carried it out, the National Institute of Health Research for funding the trial and the teams at King’s College London and the London School of Hygiene and Tropical Medicine for their work throughout. We have no disclosure.

References

  1. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, et al. Coronary bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364(17):1607-16.
  2. Perera D, Clayton T, O’Kane P, Greenwood J et al. Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 2022

Quote:

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction Divaka Perera, MD, Tim Clayton, M.Sc., Peter D. O’Kane, MD, John P. Greenwood, Ph.D., Roshan Weerackody, Ph.D., Matthew Ryan , Ph.D., Holly P. Morgan, MB, B.Ch., Matthew Dodd, M.Sc., Richard Evans, BA, Ruth Canter, M.Sc., Sophie Arnold, M.Sc., Lana J. Dixon, Ph.D., Richard J. Edwards, Ph.D., Kalpa De Silva, Ph.D., James C. Spratt, MD, Dwayne Conway, MD, James Cotton, MD, Margaret McEntegart, Ph.D. , Amedeo Chiribiri, Ph.D., Pedro Saramago, Ph.D., Anthony Gershlick, MD, Ajay M. Shah, MD, Andrew L. Clark, MD, and Mark C. Petrie, MD, for REVIVED-BCIS2 Investigators*

This article was published on August 27, 2022,
on NEJM.org. DOI: 10.1056/NEJMoa2206606
https://www.nejm.org/doi/full/10.1056/NEJMoa2206606?query=featured_home

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