The ORBITA Trial: PCI vs Placebo Procedure for Angina Relief in Stable Angina

29 Oct
October 29, 2018

Background:In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial [2], there was no difference in MI and death rates between patients with stable coronary artery disease who underwent PCI and controls. In stable angina, the primary goal of percutaneous coronary intervention (PCI) is symptomatic relief of angina, with guidelines recommending its use for those who remain symptomatic despite optimal medical management.  The issue with previous studies is both physicians and patients have not been blinded, therefore the effect size of PCI on symptomatic endpoints can be overestimated due to placebo effect as opposed to true physiological effect.  The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was designed to assess the effect of PCI versus placebo on exercise time in patients with stable ischemic symptoms in a blinded fashion.

What They Did: This was a blinded, multicenter randomized trial of that was done at 5 study sites in the UK.  After enrollment all patients received 6 weeks of medication optimization, then pre-randomization assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients then had a final follow up set of assessments before randomization and finally patients were randomized in a 1:1 fashion to PCI versus a placebo procedure for angina relief (Figure 1).

 

Figure 1: Pre-intervention optimization and assessment.

Outcomes:

  • Primary: Difference in exercise time increment between groups
  • Secondary:
    • Peak oxygen uptake (Peak VO2)
    • Change in exercise time to 1mm ST segment depression
    • Angina severity as assessed by Canadian Cardiovascular society class
    • Physical limitation
    • Angina stability
    • Angina frequency assessed with the Seattle Angina Questionnaire
    • Quality of life assessed with EQ-5D-5L questionnaire
    • Duke Treadmill score
    • Change in dobutamine stress echocardiography wall motion score index

Inclusion:

  • Age 18 – 85 years
  • Angina or equivalent symptoms
  • Patients with severe (≥70%) single-vessel stenosis

Exclusion:

  • Angiographic stenosis ≥50% in a non-target vessel
  • Acute coronary syndrome
  • Previous coronary artery bypass graft surgery
  • Left main stem coronary disease
  • Contraindications to drug-eluting stents
  • Chronic total coronary occlusion
  • Severe valvular disease
  • Severe left ventricular systolic impairment
  • Moderate to severe pulmonary hypertension
  • Life expectancy < 2years
  • Inability to give consent

Results:

  • 230 patients enrolled with ischemic symptoms and only 200 randomized to PCI vs placebo procedure
    • PCI: 105 pts
    • Placebo Procedure: 95 pts
  • Exercise Time increment:
    • Difference 16.6sec
    • 95% CI -8.9 – 42.0
    • P = 0.200
    • Not statistically significant
    • Also no differences in any of the secondary endpoints
  • Serious Adverse Events:
    • ZERO deaths
    • 4 pressure-wire related complications in the placebo group, which required PCI
    • 5 Major bleeding events (2 in the PCI group and 3 in the placebo group)

Strengths:

  • First blinded, multicenter, randomized trial of PCI for stable angina
  • An independent data safety monitoring board adjudicated all study adverse events
  • Both groups had similar duration of dual antiplatelet therapy
  • No information about the nature of the procedure was transferred from the cath lab staff to the recovery staff
  • Patients and subsequent medical caregivers were also blinded to treatment allocation
  • Study physicians present during the procedure had no further contact with the patient during the study
  • Physicians and physiologist performing cardiopulmonary exercise tests were blinded to treatment assignment
  • Funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript
  • No difference in baseline demographics between the two groups

Limitations:

  • Follow up was short and cannot address long-term myocardial infarction and mortality endpoints
  • Multiple exercise tests could potentially have a training effect from repeated tests
  • Excluded patients with ACS (for obvious reasons) and patients with severe multivessel disease and this study should have no implications on these patients undergoing PCI
  • Applicability of medically optimized patients to routine clinical population

Discussion:

  • According to the authors of the paper, single antianginal agents have been found to increase treadmill exercise time by 48 – 55s more than placebo. ORBITA was conservative in their primary outcome in trying to detect an effect size from invasive PCI of 30s
  • Medical optimization phase was more intensive than routine clinical practice. Patients were up-titrated to an average of three antianginal agents during the initial 6 weeks before randomization

Author Conclusion:“In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure.  The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.”

Clinical Take Home Point: In this study, the first blinded, multicenter, randomized trial of PCI for stable angina, the use of PCI did not provide substantial symptom relief when compared to a placebo PCI procedure in patients with stable severe coronary heart disease.  This may, however be the result of aggressive medical optimization in both groups.  Finally, the results of this study should not have implications on patients with active acute coronary syndrome or multi-vessel coronary heart disease.

References:

  1. Al-Lamee R et al. Percutaneous Coronary Intervention in Stable Angina (ORBITA): A Double-Blind, Randomised Controlled Trial. Lancet 2018. PMID: 29103656
  2. Boden WE et al. Optimal Medical Therapy With or Without PCI for Stable Coronary Disease NEJM 2007. PMID: 17287127 

Post Peer Reviewed By: Rick Pescatore, DO (Twitter: @Rick_Pescatore)

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Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of R.E.B.E.L. EM
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