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

Written by Salim Rezaie REBEL EM Medical Category: Cardiovascular

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:

Al-Lamee R et al. Percutaneous Coronary Intervention in Stable Angina (ORBITA): A Double-Blind, Randomised Controlled Trial. Lancet 2018. PMID: 29103656 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)