Dr Holly Morgan M.B., B.Ch. Clinical Research Fellow and REVIVED investigator King's College London

NEJM: Study Compares PCI to Medical Therapy to Reduce Death or Hospitalization from Heart Failure

MedicalResearch.com Interview with:

Dr Holly Morgan M.B., B.Ch. Clinical Research Fellow and REVIVED investigator King's College London

Dr. Morgan

Dr Holly Morgan M.B., B.Ch.
Clinical Research Fellow and REVIVED investigator
King’s College London

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

Response: Coronary artery disease is the commonest cause of heart failure.  Whilst individually tailored pharmacological and device therapy (optimal medical therapy, OMT) is the cornerstone of management of ischemic heart failure, rates of death and hospitalization for heart failure remain unacceptably high in this population.  Given the causative relationship between coronary disease and heart failure, coronary revascularization has long been considered as a treatment option for these patients.  Whilst 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 unsuitable for surgery); driven by the belief that hibernating myocardium will improve in function if blood flow is restored, regardless of the revascularization method.  This approach was supported in some international guidelines, though 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, when compared to OMT alone (2).  Inclusion criteria included a left ventricular ejection fraction of ≤35%, extensive coronary artery disease (British Cardiovascular Intervention Society jeopardy score ≥6, indicating significant stenoses in the left main coronary artery, proximal left anterior descending coronary artery, dominant circumflex artery, disease in multiple vessels or a combination of these) and viability in at least four dysfunctional myocardial segments which were amenable to PCI.  The main exclusion criteria were acute myocardial infarction within 4 weeks of randomisation, angina which limited the patient’s quality of life or decompensated heart failure or sustained ventricular arrhythmia within 72 hours.

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

MedicalResearch.com: What are the main findings?

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

The primary outcome occurred in 37.2% of the PCI group and 38.0% of the optimal medical therapy group (hazard ratio 0.99, p=0.96).  No differential treatment effect was observed in any of the prespecified subgroups.  Whilst LV ejection fraction improved over time, this was seen in both arms with no significant differences in the improvement at either time.  Patient reported quality of life scores improved in the PCI group, and whilst this difference was statistically significant at both 6 and 12 months, by 24 months the OMT group had caught up and the mean difference in Kansas City Cardiomyopathy Questionnaire summary score was just 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?

Response: In patients with LV dysfunction, extensive coronary disease and demonstrable myocardial viability, the addition of PCI to OMT did not reduce the incidence of death or hospitalisation from heart failure.  Furthermore, PCI did not improve left ventricular ejection fraction, although a small improvement was noted in both groups.   As a result, patients who are diagnosed with heart failure and have extensive coronary disease should not be treated with PCI.  Patients who are candidates for CABG should continue to be offered this treatment, in line with the results of the STICH trial.  As patients with recent acute myocardial infarction and limiting angina were excluded from the trial, the results should not be extrapolated into these patient populations, who should still be offered PCI on symptomatic grounds.  Despite being a high risk comorbid population, PCI was found to be safe and therefore should be offered if alternative indications are present.

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

Response: Further work is ongoing using the trial dataset to explore 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 results of REVIVED-BCIS2 call into question the hibernation hypothesis (that restoration of normal coronary perfusion through revascularization can improve left ventricular function and consequently clinical outcomes), as well as the routine use of myocardial viability testing to identify patients who may benefit from revascularization.  Specific analyses of viability studies performed for the trial may provide greater mechanistic understanding as to why revascularization with PCI failed to provide benefit, as well as rationalize the use of viability testing in this population.  Given the difference in trial populations enrolled in REVIVED and STICH, randomized comparisons of the treatments in patients who are eligible for surgical revascularization could be considered.

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

Response: The trial team would like to thank all of the patients who participated in the trial, all of the NHS and research staff who delivered it, the National Institute for 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 disclosures.

References

  1. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, et al. Coronary-artery 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

Citation:

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction Divaka Perera, M.D., Tim Clayton, M.Sc., Peter D. O’Kane, M.D., John P. Greenwood, Ph.D., Roshan Weerackody, Ph.D., Matthew Ryan, Ph.D., Holly P. Morgan, M.B., B.Ch., Matthew Dodd, M.Sc., Richard Evans, B.A., 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, M.D., Dwayne Conway, M.D., James Cotton, M.D., Margaret McEntegart, Ph.D., Amedeo Chiribiri, Ph.D., Pedro Saramago, Ph.D., Anthony Gershlick, M.D., Ajay M. Shah, M.D., Andrew L. Clark, M.D., and Mark C. Petrie, M.D., for the REVIVED-BCIS2 Investigators*

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

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